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Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis.

Identifieur interne : 001A90 ( Main/Exploration ); précédent : 001A89; suivant : 001A91

Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis.

Auteurs : Gordana Halec [Allemagne] ; Markus Schmitt [Allemagne] ; Sam Egger [Australie] ; Christian C. Abnet [États-Unis] ; Chantal Babb [Afrique du Sud] ; Sanford M. Dawsey [États-Unis] ; Christa Flechtenmacher [Allemagne] ; Tarik Gheit [France] ; Martin Hale [Afrique du Sud] ; Dana Holzinger [Allemagne] ; Reza Malekzadeh [Iran] ; Philip R. Taylor [États-Unis] ; Massimo Tommasino [France] ; Margaret I. Urban [Afrique du Sud] ; Tim Waterboer [Allemagne] ; Michael Pawlita [Allemagne] ; Freddy Sitas [Australie]

Source :

RBID : pubmed:26529033

Descripteurs français

English descriptors

Abstract

Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.

DOI: 10.1002/ijc.29911
PubMed: 26529033


Affiliations:


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Le document en format XML

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<name sortKey="Pawlita, Michael" sort="Pawlita, Michael" uniqKey="Pawlita M" first="Michael" last="Pawlita">Michael Pawlita</name>
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<name sortKey="Sitas, Freddy" sort="Sitas, Freddy" uniqKey="Sitas F" first="Freddy" last="Sitas">Freddy Sitas</name>
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<title xml:lang="en">Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis.</title>
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<name sortKey="Halec, Gordana" sort="Halec, Gordana" uniqKey="Halec G" first="Gordana" last="Halec">Gordana Halec</name>
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<nlm:affiliation>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
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<name sortKey="Schmitt, Markus" sort="Schmitt, Markus" uniqKey="Schmitt M" first="Markus" last="Schmitt">Markus Schmitt</name>
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<nlm:affiliation>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
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<name sortKey="Egger, Sam" sort="Egger, Sam" uniqKey="Egger S" first="Sam" last="Egger">Sam Egger</name>
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<nlm:affiliation>Cancer Council NSW, Cancer Research Division, Sydney, New South Wales, Australia.</nlm:affiliation>
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<name sortKey="Abnet, Christian C" sort="Abnet, Christian C" uniqKey="Abnet C" first="Christian C" last="Abnet">Christian C. Abnet</name>
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<region type="state">Maryland</region>
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<name sortKey="Babb, Chantal" sort="Babb, Chantal" uniqKey="Babb C" first="Chantal" last="Babb">Chantal Babb</name>
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<name sortKey="Dawsey, Sanford M" sort="Dawsey, Sanford M" uniqKey="Dawsey S" first="Sanford M" last="Dawsey">Sanford M. Dawsey</name>
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<nlm:affiliation>Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD.</nlm:affiliation>
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<name sortKey="Flechtenmacher, Christa" sort="Flechtenmacher, Christa" uniqKey="Flechtenmacher C" first="Christa" last="Flechtenmacher">Christa Flechtenmacher</name>
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<nlm:affiliation>Institute of Pathology, University of Heidelberg, Heidelberg, Germany.</nlm:affiliation>
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<name sortKey="Gheit, Tarik" sort="Gheit, Tarik" uniqKey="Gheit T" first="Tarik" last="Gheit">Tarik Gheit</name>
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<name sortKey="Hale, Martin" sort="Hale, Martin" uniqKey="Hale M" first="Martin" last="Hale">Martin Hale</name>
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<nlm:affiliation>Department of Anatomical Pathology, National Health Laboratory Service, Johannesburg, South Africa.</nlm:affiliation>
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<name sortKey="Holzinger, Dana" sort="Holzinger, Dana" uniqKey="Holzinger D" first="Dana" last="Holzinger">Dana Holzinger</name>
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<nlm:affiliation>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
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<name sortKey="Malekzadeh, Reza" sort="Malekzadeh, Reza" uniqKey="Malekzadeh R" first="Reza" last="Malekzadeh">Reza Malekzadeh</name>
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<nlm:affiliation>Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.</nlm:affiliation>
<country xml:lang="fr">Iran</country>
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<name sortKey="Taylor, Philip R" sort="Taylor, Philip R" uniqKey="Taylor P" first="Philip R" last="Taylor">Philip R. Taylor</name>
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<nlm:affiliation>Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda</wicri:cityArea>
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<name sortKey="Tommasino, Massimo" sort="Tommasino, Massimo" uniqKey="Tommasino M" first="Massimo" last="Tommasino">Massimo Tommasino</name>
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<nlm:affiliation>Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
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<name sortKey="Urban, Margaret I" sort="Urban, Margaret I" uniqKey="Urban M" first="Margaret I" last="Urban">Margaret I. Urban</name>
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<nlm:affiliation>National Health Laboratory Service, NHLS/MRC Cancer Epidemiology Research Group, Johannesburg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>National Health Laboratory Service, NHLS/MRC Cancer Epidemiology Research Group, Johannesburg</wicri:regionArea>
<wicri:noRegion>Johannesburg</wicri:noRegion>
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<name sortKey="Waterboer, Tim" sort="Waterboer, Tim" uniqKey="Waterboer T" first="Tim" last="Waterboer">Tim Waterboer</name>
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<nlm:affiliation>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pawlita, Michael" sort="Pawlita, Michael" uniqKey="Pawlita M" first="Michael" last="Pawlita">Michael Pawlita</name>
<affiliation wicri:level="3">
<nlm:affiliation>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Sitas, Freddy" sort="Sitas, Freddy" uniqKey="Sitas F" first="Freddy" last="Sitas">Freddy Sitas</name>
<affiliation wicri:level="1">
<nlm:affiliation>Cancer Council NSW, Cancer Research Division, Sydney, New South Wales, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Cancer Council NSW, Cancer Research Division, Sydney, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">International journal of cancer</title>
<idno type="eISSN">1097-0215</idno>
<imprint>
<date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Aged</term>
<term>Carcinogenesis (genetics)</term>
<term>Carcinoma, Squamous Cell (epidemiology)</term>
<term>Carcinoma, Squamous Cell (genetics)</term>
<term>Carcinoma, Squamous Cell (virology)</term>
<term>China</term>
<term>Esophageal Neoplasms (epidemiology)</term>
<term>Esophageal Neoplasms (genetics)</term>
<term>Esophageal Neoplasms (virology)</term>
<term>Female</term>
<term>Genotype</term>
<term>Human papillomavirus 16 (genetics)</term>
<term>Human papillomavirus 16 (pathogenicity)</term>
<term>Human papillomavirus 18 (genetics)</term>
<term>Human papillomavirus 18 (pathogenicity)</term>
<term>Humans</term>
<term>Iran</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Oncogene Proteins, Viral (genetics)</term>
<term>Repressor Proteins (genetics)</term>
<term>South Africa</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Carcinogenèse (génétique)</term>
<term>Carcinome épidermoïde (génétique)</term>
<term>Carcinome épidermoïde (virologie)</term>
<term>Carcinome épidermoïde (épidémiologie)</term>
<term>Chine</term>
<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Iran</term>
<term>Mâle</term>
<term>Papillomavirus humain de type 16 (génétique)</term>
<term>Papillomavirus humain de type 16 (pathogénicité)</term>
<term>Papillomavirus humain de type 18 (génétique)</term>
<term>Papillomavirus humain de type 18 (pathogénicité)</term>
<term>Protéines de répression (génétique)</term>
<term>Protéines des oncogènes viraux (génétique)</term>
<term>République d'Afrique du Sud</term>
<term>Sujet âgé</term>
<term>Tumeurs de l'oesophage (génétique)</term>
<term>Tumeurs de l'oesophage (virologie)</term>
<term>Tumeurs de l'oesophage (épidémiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Oncogene Proteins, Viral</term>
<term>Repressor Proteins</term>
</keywords>
<keywords scheme="MESH" type="geographic" xml:lang="en">
<term>China</term>
<term>Iran</term>
<term>South Africa</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en">
<term>Carcinoma, Squamous Cell</term>
<term>Esophageal Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Carcinogenesis</term>
<term>Carcinoma, Squamous Cell</term>
<term>Esophageal Neoplasms</term>
<term>Human papillomavirus 16</term>
<term>Human papillomavirus 18</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Carcinogenèse</term>
<term>Carcinome épidermoïde</term>
<term>Papillomavirus humain de type 16</term>
<term>Papillomavirus humain de type 18</term>
<term>Protéines de répression</term>
<term>Protéines des oncogènes viraux</term>
<term>Tumeurs de l'oesophage</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Human papillomavirus 16</term>
<term>Human papillomavirus 18</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Papillomavirus humain de type 16</term>
<term>Papillomavirus humain de type 18</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Carcinome épidermoïde</term>
<term>Tumeurs de l'oesophage</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Carcinoma, Squamous Cell</term>
<term>Esophageal Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr">
<term>Carcinome épidermoïde</term>
<term>Tumeurs de l'oesophage</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Aged</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Chine</term>
<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Iran</term>
<term>Mâle</term>
<term>République d'Afrique du Sud</term>
<term>Sujet âgé</term>
</keywords>
<keywords scheme="Wicri" type="geographic" xml:lang="fr">
<term>République populaire de Chine</term>
<term>Afrique du Sud</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Afrique du Sud</li>
<li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>Iran</li>
<li>États-Unis</li>
</country>
<region>
<li>Auvergne-Rhône-Alpes</li>
<li>Bade-Wurtemberg</li>
<li>District de Karlsruhe</li>
<li>Maryland</li>
<li>Rhône-Alpes</li>
</region>
<settlement>
<li>Heidelberg</li>
<li>Lyon</li>
</settlement>
</list>
<tree>
<country name="Allemagne">
<region name="Bade-Wurtemberg">
<name sortKey="Halec, Gordana" sort="Halec, Gordana" uniqKey="Halec G" first="Gordana" last="Halec">Gordana Halec</name>
</region>
<name sortKey="Flechtenmacher, Christa" sort="Flechtenmacher, Christa" uniqKey="Flechtenmacher C" first="Christa" last="Flechtenmacher">Christa Flechtenmacher</name>
<name sortKey="Holzinger, Dana" sort="Holzinger, Dana" uniqKey="Holzinger D" first="Dana" last="Holzinger">Dana Holzinger</name>
<name sortKey="Pawlita, Michael" sort="Pawlita, Michael" uniqKey="Pawlita M" first="Michael" last="Pawlita">Michael Pawlita</name>
<name sortKey="Schmitt, Markus" sort="Schmitt, Markus" uniqKey="Schmitt M" first="Markus" last="Schmitt">Markus Schmitt</name>
<name sortKey="Waterboer, Tim" sort="Waterboer, Tim" uniqKey="Waterboer T" first="Tim" last="Waterboer">Tim Waterboer</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Egger, Sam" sort="Egger, Sam" uniqKey="Egger S" first="Sam" last="Egger">Sam Egger</name>
</noRegion>
<name sortKey="Sitas, Freddy" sort="Sitas, Freddy" uniqKey="Sitas F" first="Freddy" last="Sitas">Freddy Sitas</name>
</country>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Abnet, Christian C" sort="Abnet, Christian C" uniqKey="Abnet C" first="Christian C" last="Abnet">Christian C. Abnet</name>
</region>
<name sortKey="Dawsey, Sanford M" sort="Dawsey, Sanford M" uniqKey="Dawsey S" first="Sanford M" last="Dawsey">Sanford M. Dawsey</name>
<name sortKey="Taylor, Philip R" sort="Taylor, Philip R" uniqKey="Taylor P" first="Philip R" last="Taylor">Philip R. Taylor</name>
</country>
<country name="Afrique du Sud">
<noRegion>
<name sortKey="Babb, Chantal" sort="Babb, Chantal" uniqKey="Babb C" first="Chantal" last="Babb">Chantal Babb</name>
</noRegion>
<name sortKey="Hale, Martin" sort="Hale, Martin" uniqKey="Hale M" first="Martin" last="Hale">Martin Hale</name>
<name sortKey="Urban, Margaret I" sort="Urban, Margaret I" uniqKey="Urban M" first="Margaret I" last="Urban">Margaret I. Urban</name>
</country>
<country name="France">
<region name="Auvergne-Rhône-Alpes">
<name sortKey="Gheit, Tarik" sort="Gheit, Tarik" uniqKey="Gheit T" first="Tarik" last="Gheit">Tarik Gheit</name>
</region>
<name sortKey="Tommasino, Massimo" sort="Tommasino, Massimo" uniqKey="Tommasino M" first="Massimo" last="Tommasino">Massimo Tommasino</name>
</country>
<country name="Iran">
<noRegion>
<name sortKey="Malekzadeh, Reza" sort="Malekzadeh, Reza" uniqKey="Malekzadeh R" first="Reza" last="Malekzadeh">Reza Malekzadeh</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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