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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">p.Arg72Pro polymorphism of <italic>P53</italic> and breast cancer risk: a meta-analysis of case-control studies</title><author><name sortKey="Diakite, Brehima" sort="Diakite, Brehima" uniqKey="Diakite B" first="Brehima" last="Diakite">Brehima Diakite</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation></author><author><name sortKey="Kassogue, Yaya" sort="Kassogue, Yaya" uniqKey="Kassogue Y" first="Yaya" last="Kassogue">Yaya Kassogue</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation></author><author><name sortKey="Dolo, Guimogo" sort="Dolo, Guimogo" uniqKey="Dolo G" first="Guimogo" last="Dolo">Guimogo Dolo</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Neuschler, Erin" sort="Neuschler, Erin" uniqKey="Neuschler E" first="Erin" last="Neuschler">Erin Neuschler</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.185648.6</institution-id><institution-id institution-id-type="ISNI">0000 0001 2175 0319</institution-id><institution>Department of Radiology,</institution><institution>College of Medicine, University of Illinois at Chicago,</institution></institution-wrap>Chicago, IL 60612 USA</nlm:aff></affiliation></author><author><name sortKey="Kassogue, Oumar" sort="Kassogue, Oumar" uniqKey="Kassogue O" first="Oumar" last="Kassogue">Oumar Kassogue</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Keita, Mamadou L" sort="Keita, Mamadou L" uniqKey="Keita M" first="Mamadou L" last="Keita">Mamadou L. Keita</name><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Traore, Cheick B" sort="Traore, Cheick B" uniqKey="Traore C" first="Cheick B" last="Traore">Cheick B. Traore</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Kamate, Bakarou" sort="Kamate, Bakarou" uniqKey="Kamate B" first="Bakarou" last="Kamate">Bakarou Kamate</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Dembele, Etienne" sort="Dembele, Etienne" uniqKey="Dembele E" first="Etienne" last="Dembele">Etienne Dembele</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Nadifi, Sellama" sort="Nadifi, Sellama" uniqKey="Nadifi S" first="Sellama" last="Nadifi">Sellama Nadifi</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.412148.a</institution-id><institution-id institution-id-type="ISNI">0000 0001 2180 2473</institution-id><institution>Hassan II University Aïn chock,</institution></institution-wrap>20000 Casablanca,19, Rue Tarik Ibnou Ziad, Morocco</nlm:aff></affiliation></author><author><name sortKey="Murphy, Robert L" sort="Murphy, Robert L" uniqKey="Murphy R" first="Robert L" last="Murphy">Robert L. Murphy</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Doumbia, Seydou" sort="Doumbia, Seydou" uniqKey="Doumbia S" first="Seydou" last="Doumbia">Seydou Doumbia</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Hou, Lifang" sort="Hou, Lifang" uniqKey="Hou L" first="Lifang" last="Hou">Lifang Hou</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Maiga, Mamoudou" sort="Maiga, Mamoudou" uniqKey="Maiga M" first="Mamoudou" last="Maiga">Mamoudou Maiga</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">33076844</idno><idno type="pmc">7574232</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574232</idno><idno type="RBID">PMC:7574232</idno><idno type="doi">10.1186/s12881-020-01133-8</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000038</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000038</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">p.Arg72Pro polymorphism of <italic>P53</italic> and breast cancer risk: a meta-analysis of case-control studies</title><author><name sortKey="Diakite, Brehima" sort="Diakite, Brehima" uniqKey="Diakite B" first="Brehima" last="Diakite">Brehima Diakite</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation></author><author><name sortKey="Kassogue, Yaya" sort="Kassogue, Yaya" uniqKey="Kassogue Y" first="Yaya" last="Kassogue">Yaya Kassogue</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation></author><author><name sortKey="Dolo, Guimogo" sort="Dolo, Guimogo" uniqKey="Dolo G" first="Guimogo" last="Dolo">Guimogo Dolo</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Neuschler, Erin" sort="Neuschler, Erin" uniqKey="Neuschler E" first="Erin" last="Neuschler">Erin Neuschler</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.185648.6</institution-id><institution-id institution-id-type="ISNI">0000 0001 2175 0319</institution-id><institution>Department of Radiology,</institution><institution>College of Medicine, University of Illinois at Chicago,</institution></institution-wrap>Chicago, IL 60612 USA</nlm:aff></affiliation></author><author><name sortKey="Kassogue, Oumar" sort="Kassogue, Oumar" uniqKey="Kassogue O" first="Oumar" last="Kassogue">Oumar Kassogue</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Keita, Mamadou L" sort="Keita, Mamadou L" uniqKey="Keita M" first="Mamadou L" last="Keita">Mamadou L. Keita</name><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Traore, Cheick B" sort="Traore, Cheick B" uniqKey="Traore C" first="Cheick B" last="Traore">Cheick B. Traore</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Kamate, Bakarou" sort="Kamate, Bakarou" uniqKey="Kamate B" first="Bakarou" last="Kamate">Bakarou Kamate</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Dembele, Etienne" sort="Dembele, Etienne" uniqKey="Dembele E" first="Etienne" last="Dembele">Etienne Dembele</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Nadifi, Sellama" sort="Nadifi, Sellama" uniqKey="Nadifi S" first="Sellama" last="Nadifi">Sellama Nadifi</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.412148.a</institution-id><institution-id institution-id-type="ISNI">0000 0001 2180 2473</institution-id><institution>Hassan II University Aïn chock,</institution></institution-wrap>20000 Casablanca,19, Rue Tarik Ibnou Ziad, Morocco</nlm:aff></affiliation></author><author><name sortKey="Murphy, Robert L" sort="Murphy, Robert L" uniqKey="Murphy R" first="Robert L" last="Murphy">Robert L. Murphy</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Doumbia, Seydou" sort="Doumbia, Seydou" uniqKey="Doumbia S" first="Seydou" last="Doumbia">Seydou Doumbia</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Teaching Hospital Center of Point G, 333 Bamako, Mali</nlm:aff></affiliation></author><author><name sortKey="Hou, Lifang" sort="Hou, Lifang" uniqKey="Hou L" first="Lifang" last="Hou">Lifang Hou</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author><author><name sortKey="Maiga, Mamoudou" sort="Maiga, Mamoudou" uniqKey="Maiga M" first="Mamoudou" last="Maiga">Mamoudou Maiga</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</nlm:aff></affiliation></author></analytic><series><title level="j">BMC Medical Genetics</title><idno type="eISSN">1471-2350</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">The effect of the p.Arg72Pro variant of the <italic>P53</italic> gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of <italic>P53</italic> gene with the risk of breast cancer.</p></sec><sec><title>Methods</title><p id="Par2">Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the <italic>TP53 </italic>p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot.</p></sec><sec><title>Results</title><p id="Par3">Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that <italic>TP53</italic> p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02–1.16, <italic>P</italic> = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01–1.17, <italic>P</italic> = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97–1.18, <italic>P</italic> = 0.19). According to the ethnic group analysis, <italic>Pro</italic> allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (<italic>P</italic> = 0.02), and Africans for the recessive model and additive model (<italic>P</italic> = 0.03).</p></sec><sec><title>Conclusions</title><p id="Par4">This meta-analysis found a significant association between <italic>TP53</italic> p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one <italic>Pro</italic> allele <italic>were</italic> more likely to have breast cancer than individuals harboring the <italic>A</italic>rg allele.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I Soerjomataram</name></author><author><name sortKey="Siegel, Rl" uniqKey="Siegel R">RL Siegel</name></author><author><name sortKey="Torre, La" uniqKey="Torre L">LA Torre</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J Ferlay</name></author><author><name sortKey="Shin, H R" uniqKey="Shin H">H-R Shin</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F 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<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Med Genet</journal-id><journal-id journal-id-type="iso-abbrev">BMC Med Genet</journal-id><journal-title-group><journal-title>BMC Medical Genetics</journal-title></journal-title-group><issn pub-type="epub">1471-2350</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">33076844</article-id><article-id pub-id-type="pmc">7574232</article-id><article-id pub-id-type="publisher-id">1133</article-id><article-id pub-id-type="doi">10.1186/s12881-020-01133-8</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>p.Arg72Pro polymorphism of <italic>P53</italic> and breast cancer risk: a meta-analysis of case-control studies</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-8296-5292</contrib-id><name><surname>Diakite</surname><given-names>Brehima</given-names></name><address><email>br.diakite@yahoo.fr</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kassogue</surname><given-names>Yaya</given-names></name><address><email>Kassoy2@yahoo.fr</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Dolo</surname><given-names>Guimogo</given-names></name><address><email>dolo@icermali.org</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jun</given-names></name><address><email>j-wang4@northwestern.edu</email></address><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Neuschler</surname><given-names>Erin</given-names></name><address><email>eneuschl@uic.edu</email></address><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Kassogue</surname><given-names>Oumar</given-names></name><address><email>oumaokya@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Keita</surname><given-names>Mamadou L</given-names></name><address><email>bakeita2010@yahoo.fr</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Traore</surname><given-names>Cheick B</given-names></name><address><email>cheickbtraore@yahoo.fr</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kamate</surname><given-names>Bakarou</given-names></name><address><email>kamatebak@yahoo.fr</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dembele</surname><given-names>Etienne</given-names></name><address><email>dembeleetienne525@yahoo.com</email></address><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Nadifi</surname><given-names>Sellama</given-names></name><address><email>nadifisel@yahoo.fr</email></address><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Murphy</surname><given-names>Robert L</given-names></name><address><email>r-murphy@northwestern.edu</email></address><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Doumbia</surname><given-names>Seydou</given-names></name><address><email>sdoumbi@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Hou</surname><given-names>Lifang</given-names></name><address><email>l-hou@northwestern.edu</email></address><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Maiga</surname><given-names>Mamoudou</given-names></name><address><email>mamoudou.maiga@northwestern.edu</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.461088.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 0567 336X</institution-id><institution>Faculty of Medicine and Odontostomatology, 1805,</institution><institution>Université des Sciences, des Techniques et des Technologies Sciences de Bamako (USTTB),</institution></institution-wrap>Hamdallaye ACI, 2000 Bamako, Mali</aff><aff id="Aff2"><label>2</label>Teaching Hospital Center of Point G, 333 Bamako, Mali</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Preventive Medicine Department, Cancer Epidemiology and Prevention,</institution><institution>Northwestern University,</institution></institution-wrap>Chicago, IL 60611 USA</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="GRID">grid.16753.36</institution-id><institution-id institution-id-type="ISNI">0000 0001 2299 3507</institution-id><institution>Institute for Global Health, Northwestern University,</institution></institution-wrap>IL60611, Chicago, USA</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="GRID">grid.185648.6</institution-id><institution-id institution-id-type="ISNI">0000 0001 2175 0319</institution-id><institution>Department of Radiology,</institution><institution>College of Medicine, University of Illinois at Chicago,</institution></institution-wrap>Chicago, IL 60612 USA</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="GRID">grid.412148.a</institution-id><institution-id institution-id-type="ISNI">0000 0001 2180 2473</institution-id><institution>Hassan II University Aïn chock,</institution></institution-wrap>20000 Casablanca,19, Rue Tarik Ibnou Ziad, Morocco</aff></contrib-group><pub-date pub-type="epub"><day>19</day><month>10</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>19</day><month>10</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>21</volume><elocation-id>206</elocation-id><history><date date-type="received"><day>22</day><month>11</month><year>2019</year></date><date date-type="accepted"><day>24</day><month>9</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s) 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated in a credit line to the data.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p id="Par1">The effect of the p.Arg72Pro variant of the <italic>P53</italic> gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of <italic>P53</italic> gene with the risk of breast cancer.</p></sec><sec><title>Methods</title><p id="Par2">Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the <italic>TP53 </italic>p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot.</p></sec><sec><title>Results</title><p id="Par3">Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that <italic>TP53</italic> p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02–1.16, <italic>P</italic> = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01–1.17, <italic>P</italic> = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97–1.18, <italic>P</italic> = 0.19). According to the ethnic group analysis, <italic>Pro</italic> allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (<italic>P</italic> = 0.02), and Africans for the recessive model and additive model (<italic>P</italic> = 0.03).</p></sec><sec><title>Conclusions</title><p id="Par4">This meta-analysis found a significant association between <italic>TP53</italic> p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one <italic>Pro</italic> allele <italic>were</italic> more likely to have breast cancer than individuals harboring the <italic>A</italic>rg allele.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd><italic>P53</italic> gene</kwd><kwd>p.Arg/pro polymorphism</kwd><kwd>Breast cancer</kwd><kwd>Meta-analysis</kwd></kwd-group><funding-group><award-group><funding-source><institution>HBNU Fellowship Fogarty International Center and the National Institutes </institution></funding-source><award-id>D43 TW010543</award-id><principal-award-recipient><name><surname>Diakite</surname><given-names>Brehima</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Background</title><p id="Par15">Breast cancer is a multifactorial disease which constitutes a major public health problem [<xref ref-type="bibr" rid="CR1">1</xref>]. In 2018, the World Health Organization reported that 2.09 million new cases of breast cancer were detected [<xref ref-type="bibr" rid="CR1">1</xref>] compared to 1.38 million cases in 2008 [<xref ref-type="bibr" rid="CR2">2</xref>]. It is the leading cause of death in women around the world. It should be noted that the incidence of breast cancer differs among different populations around the world [<xref ref-type="bibr" rid="CR1">1</xref>]. Over the past decades, major advances have been made in understanding the pathology of breast cancer at the molecular level, including the involvement of certain genes associated with the development of the disease such as <italic>BRCA1</italic>, <italic>BRCA2</italic> and <italic>P53</italic> which produce tumor suppressor proteins and participate in damaged DNA repair [<xref ref-type="bibr" rid="CR3">3</xref>–<xref ref-type="bibr" rid="CR5">5</xref>]. <italic>P53</italic> plays a key role in the regulation of cell proliferation and apoptosis. The P53 protein is essential for maintaining the integrity of the cell and its components. In human cancers, mutated <italic>P53</italic> produces abnormal proteins that alter or inhibit transcriptional regulation [<xref ref-type="bibr" rid="CR6">6</xref>]. As a result, the stress response, cell cycle as well as apoptosis are affected. Inactivation or mutation of <italic>P53</italic> gene would lead in linkage disequilibrium in the DNA sequence, which, associated with chromosomal aberrations induce the appearance of genomic instability and later the development of cancer [<xref ref-type="bibr" rid="CR7">7</xref>, <xref ref-type="bibr" rid="CR8">8</xref>]. The molecular signature of human cancers shows that this gene is frequently observed in its mutated form [<xref ref-type="bibr" rid="CR9">9</xref>]. <italic>P53</italic> has been mapped on chromosome <italic>17p13</italic> and contains 11 exons. Several single nucleotide polymorphisms (SNP) have been identified and the most studied variant is the substitution of Arginine by Proline at position 72 in exon 4. Studies carried out on different populations around the world have shown that this SNP is associated with the development of numerous diseases including cancers [<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR11">11</xref>]. It should be noted that, many association studies have examined the relationship between the SNP p.Arg72Pro of <italic>P53</italic> gene and the risk of breast cancer, however, the reports from these studies remain conflicting as some studies have shown that p.Arg72Pro is associated with the risk of breast cancer, while others found no association. Menzel et al. 2004 [<xref ref-type="bibr" rid="CR12">12</xref>] and Akkiprik et al. 2009 [<xref ref-type="bibr" rid="CR13">13</xref>] in their investigations showed a link between p.Arg72Pro and the risk of breast cancer. However, other authors who carried out a case-control study in which participants ages were not matched in a similar population, have concluded that p.Arg72Pro was not associated with the risk of breast cancer [<xref ref-type="bibr" rid="CR14">14</xref>]. These different results with diverging conclusions can be explained by a very strong heterogeneity in allele and genotype distribution of p.Arg72Pro of the <italic>P53</italic> gene. This heterogeneity may be related not only to the geographic and ethnic origin [<xref ref-type="bibr" rid="CR15">15</xref>–<xref ref-type="bibr" rid="CR17">17</xref>] but also to the study design such as non-age-matched case-control studies. Based on these above observations, we hypothesized that the p.Arg72Pro polymorphism of <italic>P53</italic> gene may represent a potentially important genetic marker, contributing to breast cancer susceptibility in Caucasian, Asians and Africans. The present meta-analysis included only age-matched case-control studies in order to statistically decrease the heterogeneity between the studies, to qualitatively assess the effect of p.Arg72Pro on the risk of breast cancer. We have performed an independent two-stage meta-analysis; overall and sub-group analysis.</p></sec><sec id="Sec2"><title>Methods</title><sec id="Sec3"><title>Literature search</title><p id="Par16">The Pubmed Genetics Medical Literature Database, the Harvard University Library, and the Web of Science and Genesis Library were used to identify available articles published in English. The keywords “<italic>P53</italic>”, “p.Arg72Pro” and “polymorphism” or “mutation” or “gene” and “breast cancer”cited in the genetic association studies were used to detect and select scientific manuscripts in these databases. We also reviewed references cited in these studies to identify additional articles that were not identified by our research in the databases.</p></sec><sec id="Sec4"><title>Inclusion criteria</title><p id="Par17">The inclusion criteria included: (1) published case-control studies as an original article to evaluate the association between p.Arg72Pro of the <italic>P53</italic> gene and the risk of breast cancer, (2) full manuscript available, (3) case-control study with age-matched, (4) distribution of genotype respecting Hardy-Weinberg equilibrium (HWE) in controls, (5) availability of the three genotypic frequencies (<italic>Arg/Arg</italic>, <italic>Arg/Pro</italic> and <italic>Pro/Pro</italic>) in the case and control groups. (6) Study no influencing the pooled odd ratio (OR) values. Three investigators independently evaluated each study to determine eligibility.</p></sec><sec id="Sec5"><title>Data extraction</title><p id="Par18">The data were collected by an investigator and verified by a second investigator to reach consensus on all points. First author, year of publication, country, ethnicity of study population, sample size, age-matched, distribution of genotype andalleles, as well as the recalculation of HWE in controls were extracted from the eligible studies. A third reviewer made a contradictory assessment to reconcile the assumptions. The data of controls evaluated with p.Arg72Pro variant were included in this meta-analysis.</p></sec><sec id="Sec6"><title>Statistical analysis</title><p id="Par19">Chi<sup>2</sup> analysis with a significance level of <italic>P</italic> < 0.05 was used to evaluate whether p.Arg72Pro polymorphism distribution of the <italic>P53</italic> gene in controls fits HWE. The association between the p.Arg72Pro and the risk of breast cancer was evaluated by the Odd ratio (OR) of 95% CI. We evaluated the strength of association between the p.Arg72Pro polymorphism of <italic>P53</italic> gene and the risk of breast cancer using different genetic models, including the dominant (<italic>Pro/Pro</italic> + <italic>Arg/Pro</italic> vs. <italic>Arg/Arg</italic>), recessive (<italic>Pro/Pro</italic> vs. <italic>Arg/Arg</italic> + <italic>Arg/Pro</italic>) and the additive (<italic>Pro</italic> vs. <italic>Arg</italic>). Heterogeneity among the studies was assessed by I<sup>2</sup> statistical test [<xref ref-type="bibr" rid="CR18">18</xref>, <xref ref-type="bibr" rid="CR19">19</xref>]. If I<sup>2</sup> > 50% (presence of heterogeneity), the random effects model was used to calculate the overall OR, otherwise in case of lack of heterogeneity, the fixed effects method was used. We also have examined the funnel plot to determine publication bias [<xref ref-type="bibr" rid="CR20">20</xref>]. All statistical analyses were performed with Review Manager Software version 5.1.</p></sec></sec><sec id="Sec7"><title>Results</title><sec id="Sec8"><title>Characteristic of eligible studies</title><p id="Par20">Figure <xref rid="Fig1" ref-type="fig">1</xref> summarizes the process of selecting studies that the inclusion criteria. In sum, 21 eligible age-matched case-control studies were selected for the pooled OR analyses. Genotype distribution of the control population that met HWE was a minimum requirement for studies to be retained for the meta-analysis. Out of the 21 studies (7841cases and8876 controls), eleven were Caucasians [<xref ref-type="bibr" rid="CR12">12</xref>–<xref ref-type="bibr" rid="CR14">14</xref>, <xref ref-type="bibr" rid="CR23">23</xref>–<xref ref-type="bibr" rid="CR28">28</xref>, <xref ref-type="bibr" rid="CR36">36</xref>, <xref ref-type="bibr" rid="CR37">37</xref>], nine were Asians [<xref ref-type="bibr" rid="CR21">21</xref>, <xref ref-type="bibr" rid="CR29">29</xref>–<xref ref-type="bibr" rid="CR35">35</xref>, <xref ref-type="bibr" rid="CR38">38</xref>] and one was African [<xref ref-type="bibr" rid="CR22">22</xref>] (Table <xref rid="Tab1" ref-type="table">1</xref>).
<fig id="Fig1"><label>Fig. 1</label><caption><p>Flow diagram of the studies evaluated for meta-analysis</p></caption><graphic xlink:href="12881_2020_1133_Fig1_HTML" id="MO1"></graphic></fig><table-wrap id="Tab1"><label>Table 1</label><caption><p>Genotypes distribution of <italic>TP53</italic> p.Arg72Pro in breast cancer cases and controls</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th></th><th></th><th colspan="3">Cases</th><th></th><th colspan="3">Controls</th><th></th></tr><tr><th>Authors</th><th>Ethnicity</th><th>N</th><th><bold><italic>Arg/Arg</italic></bold></th><th><bold><italic>Arg/Pro</italic></bold></th><th><bold><italic>Pro/Pro</italic></bold></th><th>N</th><th><bold><italic>Arg/Arg</italic></bold></th><th><bold><italic>Arg/Pro</italic></bold></th><th><bold><italic>Pro/Pro</italic></bold></th><th>HWE</th></tr></thead><tbody><tr><td>Akkiprik et al. 2009 [<xref ref-type="bibr" rid="CR13">13</xref>]</td><td>Caucasian</td><td>95</td><td>25</td><td>50</td><td>20</td><td>107</td><td>46</td><td>49</td><td>12</td><td>Yes</td></tr><tr><td>Alshatwi et al. 2012 [<xref ref-type="bibr" rid="CR21">21</xref>]</td><td>Asian</td><td>100</td><td>22</td><td>52</td><td>26</td><td>100</td><td>32</td><td>51</td><td>17</td><td>Yes</td></tr><tr><td>Ayoubi et al. 2018 [<xref ref-type="bibr" rid="CR22">22</xref>]</td><td>African</td><td>125</td><td>55</td><td>42</td><td>28</td><td>126</td><td>65</td><td>46</td><td>15</td><td>Yes</td></tr><tr><td>Buyru et al. 2003 [<xref ref-type="bibr" rid="CR23">23</xref>]</td><td>Caucasian</td><td>115</td><td>64</td><td>39</td><td>12</td><td>63</td><td>26</td><td>28</td><td>9</td><td>Yes</td></tr><tr><td>Cherdyntseva et al. 2012 [<xref ref-type="bibr" rid="CR24">24</xref>]</td><td>Caucasian</td><td>388</td><td>184</td><td>162</td><td>42</td><td>275</td><td>148</td><td>100</td><td>27</td><td>Yes</td></tr><tr><td>Costa et al. 2008 [<xref ref-type="bibr" rid="CR25">25</xref>]</td><td>Caucasian</td><td>175</td><td>98</td><td>61</td><td>16</td><td>212</td><td>124</td><td>70</td><td>18</td><td>Yes</td></tr><tr><td>Cox et al. 2007 [<xref ref-type="bibr" rid="CR26">26</xref>]</td><td>Caucasian</td><td>1477</td><td>804</td><td>569</td><td>104</td><td>2224</td><td>1255</td><td>838</td><td>131</td><td>Yes</td></tr><tr><td>Denisov et al. 2009 [<xref ref-type="bibr" rid="CR27">27</xref>]</td><td>Caucasian</td><td>297</td><td>148</td><td>124</td><td>25</td><td>275</td><td>147</td><td>99</td><td>29</td><td>Yes</td></tr><tr><td>Ebner et al. 2010 [<xref ref-type="bibr" rid="CR28">28</xref>]</td><td>Caucasian</td><td>263</td><td>138</td><td>108</td><td>17</td><td>254</td><td>137</td><td>103</td><td>14</td><td>Yes</td></tr><tr><td>Hossain et al. 2016 [<xref ref-type="bibr" rid="CR29">29</xref>]</td><td>Asian</td><td>125</td><td>54</td><td>42</td><td>29</td><td>125</td><td>61</td><td>51</td><td>13</td><td>Yes</td></tr><tr><td>Isakova et al. 2017 [<xref ref-type="bibr" rid="CR30">30</xref>]</td><td>Asian</td><td>117</td><td>57</td><td>50</td><td>10</td><td>102</td><td>53</td><td>36</td><td>13</td><td>Yes</td></tr><tr><td>Katiyar et al. 2003 [<xref ref-type="bibr" rid="CR31">31</xref>]</td><td>Asian</td><td>77</td><td>20</td><td>51</td><td>6</td><td>41</td><td>9</td><td>24</td><td>8</td><td>Yes</td></tr><tr><td>krivokuca et al. 2014 [<xref ref-type="bibr" rid="CR14">14</xref>]</td><td>Caucasian</td><td>155</td><td>87</td><td>58</td><td>10</td><td>114</td><td>62</td><td>45</td><td>7</td><td>Yes</td></tr><tr><td>Li et al. 2002 [<xref ref-type="bibr" rid="CR32">32</xref>]</td><td>Asian</td><td>28</td><td>11</td><td>10</td><td>7</td><td>50</td><td>10</td><td>26</td><td>14</td><td>Yes</td></tr><tr><td>Ma et al. 2006 [<xref ref-type="bibr" rid="CR33">33</xref>]</td><td>Asian</td><td>404</td><td>149</td><td>178</td><td>77</td><td>472</td><td>150</td><td>222</td><td>100</td><td>Yes</td></tr><tr><td>Menzel et al. 2004 [<xref ref-type="bibr" rid="CR12">12</xref>]</td><td>Caucasian</td><td>302</td><td>158</td><td>114</td><td>30</td><td>475</td><td>275</td><td>170</td><td>30</td><td>Yes</td></tr><tr><td>Sharma et al. 2014 [<xref ref-type="bibr" rid="CR34">34</xref>]</td><td>Asian</td><td>200</td><td>47</td><td>103</td><td>50</td><td>200</td><td>67</td><td>91</td><td>42</td><td>Yes</td></tr><tr><td>Song et al. 2009 [<xref ref-type="bibr" rid="CR35">35</xref>]</td><td>Asian</td><td>1110</td><td>341</td><td>547</td><td>222</td><td>1097</td><td>355</td><td>514</td><td>228</td><td>Yes</td></tr><tr><td>Sprague et al. 2007 [<xref ref-type="bibr" rid="CR36">36</xref>]</td><td>Caucasian</td><td>1653</td><td>909</td><td>644</td><td>100</td><td>1854</td><td>1021</td><td>704</td><td>129</td><td>yes</td></tr><tr><td>Wang-Gohrke et al. 2002 [<xref ref-type="bibr" rid="CR37">37</xref>]</td><td>Caucasian</td><td>552</td><td>282</td><td>221</td><td>49</td><td>543</td><td>300</td><td>203</td><td>40</td><td>yes</td></tr><tr><td>Zhang et al. 2007 [<xref ref-type="bibr" rid="CR38">38</xref>]</td><td>Asian</td><td>83</td><td>21</td><td>45</td><td>17</td><td>167</td><td>47</td><td>87</td><td>33</td><td>yes</td></tr></tbody></table><table-wrap-foot><p><italic>N</italic> Number, <italic>HWE</italic>, Hardy-Weinberg Equilibrium</p></table-wrap-foot></table-wrap></p></sec><sec id="Sec9"><title>Quantitative analysis</title><p id="Par21">Table <xref rid="Tab2" ref-type="table">2</xref> shows pooled ORs and heterogeneity testresults of the association between the <italic>TP53</italic> p.Arg72Pro polymorphism and the risk of breast cancer. Overall, a slightly association of <italic>TP53</italic> p.Arg72Pro polymorphism with the risk of breast cancer was observed for the dominant (OR = 1.09, 95% CI = 1.02–1.16, <italic>P</italic> = 0.01, Fig. <xref rid="Fig2" ref-type="fig">2</xref>) and additive (OR = 1.09, 95% CI = 1.01–1.17, <italic>P</italic> = 0.03, Fig. <xref rid="Fig3" ref-type="fig">3</xref>) models, but not for the recessive model (OR = 1.07, 95% CI = 0.97–1.18, <italic>P</italic> = 0.19, Fig. <xref rid="Fig4" ref-type="fig">4</xref>). In the subgroup analyzes, except the recessive model (OR = 1.18, 95% CI = 0.96–1.44; <italic>P</italic> = 0.12), we noted a moderate association of p. Arg72Pro with the risk of breast cancer for the dominant (OR = 1.09, 95% CI = 1.01–1.17, <italic>P</italic> = 0.02) and additive (OR = 1.07, 95% CI = 1.01–1.14, <italic>P</italic> = 0.02) models in Caucasians (Fig. <xref rid="Fig5" ref-type="fig">5</xref>). When considering the Asian population, the different genetic models showed no trend (recessive: OR = 1.01, 95% CI = 0.87–1.17, <italic>P</italic> = 0.88; dominant: OR = 1.06, 95% CI = 0.94–1.20; <italic>P</italic> = 0.33; additive; OR = 1.06, 95% CI = 0.91–1.23, <italic>P</italic> = 0.46) (Fig. <xref rid="Fig6" ref-type="fig">6</xref>). The only eligible African study showed that the <italic>TP53</italic> p.Arg72Pro polymorphism is highly associated with the risk of breast cancer as well in the recessive model (OR = 2.14, 95% CI = 1.08–4.23, <italic>P</italic> = 0.03) than in the additive model (OR = 1.49, 95% CI = 1.03–2.16, <italic>P</italic> = 0.03).
<table-wrap id="Tab2"><label>Table 2</label><caption><p>Distribution of <italic>TP53</italic> p.Arg72Pro polymorphism according to the different genetic models</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th></th><th>Sample size</th><th>Genetic</th><th colspan="2">Pooled</th><th colspan="2">Heterogeneity</th></tr><tr><th>Group</th><th>N</th><th>Cases/Controls</th><th>Models</th><th>OR (95% CI)</th><th><italic>P</italic>-value</th><th>I<sup>2</sup></th><th>Phet</th></tr></thead><tbody><tr><td>Overall</td><td>21</td><td char="/" align="char">7841/8876</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>Dominant</td><td>1.09 (1.02–1.16) FE</td><td>0.01</td><td>31%</td><td>0.09</td></tr><tr><td></td><td></td><td></td><td>Recessive</td><td>1.07 (0.97–1.18) FE</td><td>0.19</td><td>36%</td><td>0.05</td></tr><tr><td></td><td></td><td></td><td>Additive</td><td>1.09 (1.01–1.17) FE</td><td>0.03</td><td>47%</td><td>0.01</td></tr><tr><td char="×" align="char">Caucasian</td><td>11</td><td char="/" align="char">5472/6396</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>Dominant</td><td char="×" align="char">1.09 (1.01–1.17) FE</td><td>0.02</td><td>27%</td><td char="×" align="char">0.19</td></tr><tr><td></td><td></td><td></td><td>Recessive</td><td char="×" align="char">1.09 (0.95–1.25) FE</td><td>0.22</td><td>10%</td><td char="×" align="char">0.34</td></tr><tr><td></td><td></td><td></td><td>Additive</td><td char="×" align="char">1.07 (1.01–1.14) FE</td><td>0.02</td><td>39%</td><td char="×" align="char">0.09</td></tr><tr><td>Asian</td><td>9</td><td char="/" align="char">2244/2354</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>Dominant</td><td>1.06 (0.94–1.20) FE</td><td>0.33</td><td>45%</td><td>0.07</td></tr><tr><td></td><td></td><td></td><td>Recessive</td><td>1.01 (0.87–1.17) FE</td><td>0.88</td><td>48%</td><td>0.05</td></tr><tr><td></td><td></td><td></td><td>Additive</td><td>1.06 (0.91–1.23) RE</td><td>0.46</td><td>54%</td><td>0.03</td></tr><tr><td>African</td><td>1</td><td char="/" align="char">125/126</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>Dominant</td><td>1.36 (0.83–2.23)</td><td>0.23</td><td></td><td></td></tr><tr><td></td><td></td><td></td><td>Recessive</td><td>2.14 (1.08–4.23)</td><td>0.03</td><td>–</td><td>–</td></tr><tr><td></td><td></td><td></td><td>Additive</td><td>1.49 (1.03–2.16)</td><td>0.03</td><td>–</td><td>–</td></tr></tbody></table><table-wrap-foot><p>*: Significant, P: <italic>p</italic> value OR; I<sup>2</sup>: Inconsistency; dominant model<italic>: Pro/Pro</italic> + <italic>Arg/Pro</italic> vs. <italic>Arg/Arg</italic>; recessive model: <italic>Pro/Pro</italic> vs. <italic>Arg/Arg</italic> + <italic>Arg/Pro</italic>; additive model: <italic>Pro</italic> vs. <italic>Arg</italic>; Phet: <italic>P</italic> value of Heterogeneity, <italic>FE</italic> Fixed effect, <italic>RE</italic> Random effect, <italic>N</italic> Number</p></table-wrap-foot></table-wrap><fig id="Fig2"><label>Fig. 2</label><caption><p>Forest plots of the association between breast cancer and <italic>TP53</italic> p.Arg72Pro polymorphism for the dominant model. The black diamond denotes the pooled OR; blue squares indicate the OR in each study with square sizes inversely proportional to the standard error of the OR; and horizontal lines represent the 95% CI</p></caption><graphic xlink:href="12881_2020_1133_Fig2_HTML" id="MO2"></graphic></fig><fig id="Fig3"><label>Fig. 3</label><caption><p>Forest plots of the association between breast cancer and <italic>TP53</italic> p.Arg72Pro polymorphism for the recessive model. The black diamond denotes the pooled OR; blue squares indicate the OR in each study with square sizes inversely proportional to the standard error of the OR; and horizontal lines represent the 95% CI</p></caption><graphic xlink:href="12881_2020_1133_Fig3_HTML" id="MO3"></graphic></fig><fig id="Fig4"><label>Fig. 4</label><caption><p>Forest plots of the association between breast cancer and <italic>TP53</italic> p.Arg72Pro polymorphism for the additive model. The black diamond denotes the pooled OR; blue squares indicate the OR in each study with square sizes inversely proportional to the standard error of the OR; and horizontal lines represent the 95% CI</p></caption><graphic xlink:href="12881_2020_1133_Fig4_HTML" id="MO4"></graphic></fig><fig id="Fig5"><label>Fig. 5</label><caption><p>Forest plots of the association between breast cancer and <italic>TP53</italic> p.Arg72Pro polymorphism for the <bold>a</bold> dominant model, <bold>b</bold> recessive model and <bold>c</bold> additive model in Caucasians. The black diamond denotes the pooled OR; blue squares indicate the OR in each study with square sizes inversely proportional to the standard error of the OR; and horizontal lines represent the 95% CI</p></caption><graphic xlink:href="12881_2020_1133_Fig5_HTML" id="MO5"></graphic></fig><fig id="Fig6"><label>Fig. 6</label><caption><p>Forest plots of the association between breast cancer and <italic>TP53</italic> p.Arg72Pro polymorphism for the <bold>a</bold> dominant model, <bold>b</bold> recessive model and <bold>c</bold> additive model in Asians. The black diamond denotes the pooled OR; blue squares indicate the OR in each study with square sizes inversely proportional to the standard error of the OR; and horizontal lines represent the 95% CI</p></caption><graphic xlink:href="12881_2020_1133_Fig6_HTML" id="MO6"></graphic></fig></p></sec><sec id="Sec10"><title>Sensitive analysis</title><p id="Par22">To maintain the stability of the meta-analysis after the non-inclusion of deviant studies of HWE, we evaluated the influence of each study on pooled OR. After the exclusion of studies [<xref ref-type="bibr" rid="CR39">39</xref>–<xref ref-type="bibr" rid="CR42">42</xref>],no study has shown a significant influence of pooled OR effect and <italic>p</italic>-values for the different genetic models (Table <xref rid="Tab2" ref-type="table">2</xref>).</p></sec><sec id="Sec11"><title>Sources of heterogeneity</title><p id="Par23">To avoid large heterogeneity, we excluded studies in which the distribution of genotypes deviated from the HWE equilibrium. The sensitivity analysis overall, showed moderate heterogeneity (I<sup>2</sup> < 50%) in the recessive and dominant models. We noted the same tendency of heterogeneity when considering all the data (I<sup>2</sup> = 47%, <italic>P</italic> = 0.01) and among Asians (I<sup>2</sup> = 54%, <italic>P</italic> = 0.03) for the additive model (Table <xref rid="Tab2" ref-type="table">2</xref>). In addition, we compared the pooled OR of the fixed and random effects, no statistically significant difference was found between the two effects, which supports strongly the consistency of the present study’s data.</p></sec><sec id="Sec12"><title>Publication Bias</title><p id="Par24">The publication bias was assessed using the funnel plot. After the exclusion of studies deviating from HWE and those influencing the pooled ORs values, no significant publication bias was found in the different genetic models (Fig. <xref rid="Fig7" ref-type="fig">7</xref>).
<fig id="Fig7"><label>Fig. 7</label><caption><p>Funnel plots of dominant <bold>a</bold>, recessive <bold>b</bold> and additive <bold>c</bold> model precision by OR</p></caption><graphic xlink:href="12881_2020_1133_Fig7_HTML" id="MO7"></graphic></fig></p></sec></sec><sec id="Sec13"><title>Discussion</title><p id="Par25">Like other multifactorial diseases, the causes of breast cancer are not known. However, several factors combine their effects for the development of the disease. These factors are of clinical, biological, environmental and genetic origin [<xref ref-type="bibr" rid="CR43">43</xref>, <xref ref-type="bibr" rid="CR44">44</xref>]. From a genomic point of view, it has been reported that genetic polymorphisms of the <italic>p53</italic> gene can influence the development of cancers [<xref ref-type="bibr" rid="CR45">45</xref>]. However, the mechanism by which these polymorphisms affect cancer development remain unknown. Functionally, these polymorphisms alter alternative splicing and thus affecting mRNA stability and protein synthesis. The normal <italic>P53</italic> gene produces a protein that plays a key role in DNA repair, cell cycle control and apoptosis [<xref ref-type="bibr" rid="CR45">45</xref>]. Through this physiological role P53 acts as a guardian of the genome, preventing the malignant transformation of normal cells. In the event of a mutation, the function of p53 is impaired, leading to the appearance of malignant cells and later cancerous disease [<xref ref-type="bibr" rid="CR46">46</xref>–<xref ref-type="bibr" rid="CR48">48</xref>]. It has been reported that the <italic>R72</italic> variant of the <italic>P53</italic> mutant in addition to influencing the onset of cancer is also associated with a bad prognosis through the rapid onset of metastasis [<xref ref-type="bibr" rid="CR49">49</xref>].</p><p id="Par26">In the present meta-analysis, we examined the relationship between <italic>TP53</italic> p.Arg72Pro polymorphism and the risk of breast cancer. Overall, our findings showed that the dominant and additive models were associated with an increased risk of breast cancer for the carriers of <italic>72Pro</italic> allele. These results corroborate with the data reported from two recent meta-analyzes, the first covering eleven studies with 950 cases and 882 controls in the Asian population [<xref ref-type="bibr" rid="CR50">50</xref>] and the second performed on the Indian population which covered seven studies with 1249 cases and 1838 controls [<xref ref-type="bibr" rid="CR51">51</xref>]. These authors in their analysis showed that the dominant and the additive models were associated with the risk of breast cancer. Contrary to our results, other meta-analyzes found conflicting results [<xref ref-type="bibr" rid="CR52">52</xref>, <xref ref-type="bibr" rid="CR53">53</xref>]. The works of Zhuo et al. 2009, Francisco et al. 2011, Ma et al. 2011 and Concalves et al. 2014 also reported a decreased risk of breast cancer with the different genetic models applied [<xref ref-type="bibr" rid="CR54">54</xref>–<xref ref-type="bibr" rid="CR57">57</xref>]. These differences might be explained by the samples size, types of allelic variant and eligible studies included. In the subgroup analysis, our meta-analysis revealed a high risk of breast cancer with <italic>TP53</italic> p.Arg72Pro in Caucasians (dominant model and additive model) and Africans (recessive and additive models). These trends were consistent with previous studies [<xref ref-type="bibr" rid="CR12">12</xref>, <xref ref-type="bibr" rid="CR13">13</xref>, <xref ref-type="bibr" rid="CR22">22</xref>] but inconsistent with the findings of other studies [<xref ref-type="bibr" rid="CR52">52</xref>, <xref ref-type="bibr" rid="CR53">53</xref>]. However, Jafrin et al. 2020 concluded that <italic>TP53</italic> p.Arg/Pro was associated with the risk of breast cancer in the South Asian population. The difference between the studies could be explained by the ethnicity and study design. The effects of ethnicity may be due to several factors, allelic heterogeneity, gene-gene and gene-environment interaction and linkage disequilibrium [<xref ref-type="bibr" rid="CR58">58</xref>–<xref ref-type="bibr" rid="CR61">61</xref>]. In the previous meta-analyzes, the selection criteria of studies were not sufficiently robust such as inclusion of the age-unmatched case-control studies and the inclusion of studies with control groups not satisfying HWE [<xref ref-type="bibr" rid="CR62">62</xref>–<xref ref-type="bibr" rid="CR75">75</xref>]. The major advantage of the present meta-analysis was the inclusion of a large number of samples, including very selective criteria to measure the strength of the association between this polymorphism in exon 4 of <italic>TP53</italic> gene and the risk of breast cancer using different genetic models. However, several limitations need to be highlighted, sample size and small number of case-control age-matched studies in ethnic groups.</p></sec><sec id="Sec14"><title>Conclusion</title><p id="Par27">In the light of this meta-analysis, we noticed that individuals carrying at least one <italic>Pro</italic> allele of the <italic>P53</italic> gene are more likely to have breast cancer with dominant and additive models than individuals harboring the wild-type <italic>Arg</italic> allele. Our study further strengthened and confirmed the hypothesis that the <italic>P53</italic> gene is usually mutated in about half of breast cancer cases. For the stability and homogeneity of results from meta-analysis, future similar studies should take into account selection criteria for articles such as no deviation from HWE in the control group and the matching of cases and controls according to age.</p></sec><sec sec-type="supplementary-material"><title>Supplementary information</title><sec id="Sec15"><p><supplementary-material content-type="local-data" id="MOESM1"><media xlink:href="12881_2020_1133_MOESM1_ESM.docx"><caption><p><bold>Additional file 1.</bold> Availability of all data and references with PubMed accession numbers.</p></caption></media></supplementary-material></p></sec></sec></body><back><glossary><title>Abbreviations</title><def-list><def-item><term><italic>Arg</italic></term><def><p id="Par5">Arginine</p></def></def-item><def-item><term>CI</term><def><p id="Par6">Confidence interval</p></def></def-item><def-item><term>Fig.</term><def><p id="Par7">Figure</p></def></def-item><def-item><term>HWE</term><def><p id="Par8">Hady-Weinberg Equilibrium</p></def></def-item><def-item><term>I<sup>2</sup></term><def><p id="Par9">Inconsistency</p></def></def-item><def-item><term>N</term><def><p id="Par10">Number</p></def></def-item><def-item><term>OR</term><def><p id="Par11">Odd ratio</p></def></def-item><def-item><term>P</term><def><p id="Par12"><italic>P</italic> value</p></def></def-item><def-item><term><italic>Pro</italic></term><def><p id="Par13">Proline</p></def></def-item><def-item><term>SNP</term><def><p id="Par14">Single nucleotide polymorphisms</p></def></def-item></def-list></glossary><fn-group><fn><p><bold>Publisher’s Note</bold></p><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></fn><fn><p>Lifang Hou and MamoudouMaiga are Last author.</p></fn></fn-group><sec><title>Supplementary information</title><p><bold>Supplementary information</bold> accompanies this paper at 10.1186/s12881-020-01133-8.</p></sec><ack><p>The authors thank Harvard University, Boston University, Northwestern University, and University of New Mexico (HBNU) Consortium, Global Health, Fogarty International Center and the NIH for their training support. Wealso thankthe Faculty of Medicine and Odontostomatology of the Universitédes Sciences, Techniques et Technologies de Bamako, the University Clinical Research Center (UCRC-Mali), Intelligence Center of Excellence Mali (ICER-Mali) particularly Prof Cheick Fantamady Traore, Prof. Mamadou Diakite and Dr. Mamadou Coulibaly for logistical support.</p></ack><notes notes-type="author-contribution"><title>Authors’ contributions</title><p>All authors read and approved the final manuscript. Study concept and design: BD, YK, GD, JW, EN, OK, MLK, CBT, BK, ED, SN,SD, LH, MM. Acquisition, analysis and interpretationof data: BD, YK, GD,MM. Drafting of the manuscript: BD with assistance from by YK, MM. Critical revision of the manuscript for important intellectualcontent: JW, EN, SN, GD, SD. Obtaining supervision: LH, RLM.</p></notes><notes notes-type="funding-information"><title>Funding</title><p>Research reported in this publication was supported by the HBNU Consortium, Fogarty International Center and the National Institutes of Health under Award Number D43 TW010543. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.</p></notes><notes notes-type="data-availability"><title>Availability of data and materials</title><p>The dataset analyzed for thisstudyis available from the Additional file <xref rid="MOESM1" ref-type="media">1</xref>.</p></notes><notes id="FPar1"><title>Ethics approval and consent to participate</title><p id="Par28">Not applicable.</p></notes><notes id="FPar2"><title>Consent for publication</title><p id="Par29">Not applicable.</p></notes><notes id="FPar3" notes-type="COI-statement"><title>Competing interests</title><p id="Par30">The authors declare that they have no competing interests.</p></notes><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group 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