5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia
Identifieur interne : 003B08 ( PascalFrancis/Checkpoint ); précédent : 003B07; suivant : 003B095α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia
Auteurs : Vanessa M. Hayes [Australie] ; Gianluca Severi [Australie] ; Emma J. D. Padilla [Australie] ; Howard A. Morris [Australie] ; Wayne D. Tilley [Australie] ; Melissa C. Southey [Australie, France] ; Dallas R. English [Australie] ; Robert L. Sutherland [Australie] ; John L. Hopper [Australie] ; Peter Boyle [France] ; Graham G. Giles [Australie]Source :
- International journal of cancer [ 0020-7136 ] ; 2007.
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Abstract
Controversy exists over the significance of associations between the SRD5A2 (5α-reductase type 2) polymorphisms, A49T and V89L, and risk of prostate cancer. These potentially functional polymorphisms may alter life-long exposure to androgens with subsequent effects on male health and aging. The aim of this study was to examine the association of these variants with prostate cancer risk, plasma hormone levels and androgenetic alopecia. Subjects include 827 cases and 736 controls from an Australian population-based case-control study of prostate cancer. Information on prostate cancer risk factors and patterns of balding were collected. Plasma levels of testosterone, 3a-diol glucuronide (3α-diolG), dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and estradiol were measured for controls. No associations with the V89L polymorphism were found. Carriers of the rarer A49T A allele were at a 60% higher risk of prostate cancer (OR = 1.60; 95% CI 1.09-2.36; p = 0.02) and 50% lower risk of vertex and frontal balding (p = 0.03) compared with men homozygous for the more common G allele. Although we found little evidence of association between this variant and plasma levels of 5 measured androgens, circulating 3a-diolG levels were 34% lower in A49T A allele carriers (p < 0.0001). Our study provides evidence that the SRD5A2 A49T A variant is associated with an increased risk of prostate cancer, lower levels of circulating 3a-diolG and decreased risk of baldness. These findings raise important questions with respect to previous assumptions concerning hormonal influences on prostate cancer risk in ageing males.
Affiliations:
- Australie, France
- Auvergne-Rhône-Alpes, Nouvelle-Galles du Sud, Rhône-Alpes, Victoria (État)
- Lyon, Melbourne, Sydney
- Université de Melbourne
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Hayes</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>University of New South Wales</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Cancer Epidemiology Centre, Cancer Council of Victoria</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Padilla, Emma J D" sort="Padilla, Emma J D" uniqKey="Padilla E" first="Emma J. 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Tilley</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Hanson Institute</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Hanson Institute</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Department of Pathology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>International Agency for Research on Cancer</s1><s2>Lyon</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="English, Dallas R" sort="English, Dallas R" uniqKey="English D" first="Dallas R." last="English">Dallas R. English</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Cancer Epidemiology Centre, Cancer Council of Victoria</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Sutherland, Robert L" sort="Sutherland, Robert L" uniqKey="Sutherland R" first="Robert L." last="Sutherland">Robert L. 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Hayes</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>University of New South Wales</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Cancer Epidemiology Centre, Cancer Council of Victoria</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Padilla, Emma J D" sort="Padilla, Emma J D" uniqKey="Padilla E" first="Emma J. D." last="Padilla">Emma J. D. Padilla</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Morris, Howard A" sort="Morris, Howard A" uniqKey="Morris H" first="Howard A." last="Morris">Howard A. Morris</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Hanson Institute</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Hanson Institute</wicri:noRegion></affiliation></author><author><name sortKey="Tilley, Wayne D" sort="Tilley, Wayne D" uniqKey="Tilley W" first="Wayne D." last="Tilley">Wayne D. Tilley</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Hanson Institute</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Hanson Institute</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Department of Pathology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>International Agency for Research on Cancer</s1><s2>Lyon</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="English, Dallas R" sort="English, Dallas R" uniqKey="English D" first="Dallas R." last="English">Dallas R. English</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Cancer Epidemiology Centre, Cancer Council of Victoria</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Sutherland, Robert L" sort="Sutherland, Robert L" uniqKey="Sutherland R" first="Robert L." last="Sutherland">Robert L. Sutherland</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>University of New South Wales</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Boyle, Peter" sort="Boyle, Peter" uniqKey="Boyle P" first="Peter" last="Boyle">Peter Boyle</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>International Agency for Research on Cancer</s1><s2>Lyon</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Cancer Epidemiology Centre, Cancer Council of Victoria</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author></analytic><series><title level="j" type="main">International journal of cancer</title><title level="j" type="abbreviated">Int. j. cancer</title><idno type="ISSN">0020-7136</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">International journal of cancer</title><title level="j" type="abbreviated">Int. j. cancer</title><idno type="ISSN">0020-7136</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>3-Oxo-5α-steroid 4-dehydrogenase</term><term>Androgen</term><term>Androgenetic alopecia</term><term>Australia</term><term>Blood plasma</term><term>Cancerology</term><term>Case control study</term><term>Epidemiology</term><term>Gene</term><term>Genetic variability</term><term>Genotype</term><term>Hair (head)</term><term>Human</term><term>Nephrology</term><term>Polymorphism</term><term>Prostate cancer</term><term>Risk factor</term><term>Urology</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Cancer prostate</term><term>3-Oxo-5α-steroid 4-dehydrogenase</term><term>Gène</term><term>Alopécie androgénétique</term><term>Australie</term><term>Urologie</term><term>Androgène</term><term>Variabilité génétique</term><term>Génotype</term><term>Facteur risque</term><term>Epidémiologie</term><term>Polymorphisme</term><term>Homme</term><term>Etude cas témoin</term><term>Plasma sanguin</term><term>Cancérologie</term><term>Cheveu</term><term>Néphrologie</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Australie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Controversy exists over the significance of associations between the SRD5A2 (5α-reductase type 2) polymorphisms, A49T and V89L, and risk of prostate cancer. These potentially functional polymorphisms may alter life-long exposure to androgens with subsequent effects on male health and aging. The aim of this study was to examine the association of these variants with prostate cancer risk, plasma hormone levels and androgenetic alopecia. Subjects include 827 cases and 736 controls from an Australian population-based case-control study of prostate cancer. Information on prostate cancer risk factors and patterns of balding were collected. Plasma levels of testosterone, 3a-diol glucuronide (3α-diolG), dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and estradiol were measured for controls. No associations with the V89L polymorphism were found. Carriers of the rarer A49T A allele were at a 60% higher risk of prostate cancer (OR = 1.60; 95% CI 1.09-2.36; p = 0.02) and 50% lower risk of vertex and frontal balding (p = 0.03) compared with men homozygous for the more common G allele. Although we found little evidence of association between this variant and plasma levels of 5 measured androgens, circulating 3a-diolG levels were 34% lower in A49T A allele carriers (p < 0.0001). Our study provides evidence that the SRD5A2 A49T A variant is associated with an increased risk of prostate cancer, lower levels of circulating 3a-diolG and decreased risk of baldness. These findings raise important questions with respect to previous assumptions concerning hormonal influences on prostate cancer risk in ageing males.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0020-7136</s0></fA01><fA02 i1="01"><s0>IJCNAW</s0></fA02><fA03 i2="1"><s0>Int. j. cancer</s0></fA03><fA05><s2>120</s2></fA05><fA06><s2>4</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia</s1></fA08><fA11 i1="01" i2="1"><s1>HAYES (Vanessa M.)</s1></fA11><fA11 i1="02" i2="1"><s1>SEVERI (Gianluca)</s1></fA11><fA11 i1="03" i2="1"><s1>PADILLA (Emma J. D.)</s1></fA11><fA11 i1="04" i2="1"><s1>MORRIS (Howard A.)</s1></fA11><fA11 i1="05" i2="1"><s1>TILLEY (Wayne D.)</s1></fA11><fA11 i1="06" i2="1"><s1>SOUTHEY (Melissa C.)</s1></fA11><fA11 i1="07" i2="1"><s1>ENGLISH (Dallas R.)</s1></fA11><fA11 i1="08" i2="1"><s1>SUTHERLAND (Robert L.)</s1></fA11><fA11 i1="09" i2="1"><s1>HOPPER (John L.)</s1></fA11><fA11 i1="10" i2="1"><s1>BOYLE (Peter)</s1></fA11><fA11 i1="11" i2="1"><s1>GILES (Graham G.)</s1></fA11><fA14 i1="01"><s1>Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="02"><s1>University of New South Wales</s1><s2>Sydney</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="03"><s1>Cancer Epidemiology Centre, Cancer Council of Victoria</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="04"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="05"><s1>Hanson Institute</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Pathology, University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>6 aut.</sZ></fA14><fA14 i1="08"><s1>International Agency for Research on Cancer</s1><s2>Lyon</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>10 aut.</sZ></fA14><fA20><s1>776-780</s1></fA20><fA21><s1>2007</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13027</s2><s5>354000159318100070</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>37 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>07-0130112</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>International journal of cancer</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Controversy exists over the significance of associations between the SRD5A2 (5α-reductase type 2) polymorphisms, A49T and V89L, and risk of prostate cancer. These potentially functional polymorphisms may alter life-long exposure to androgens with subsequent effects on male health and aging. The aim of this study was to examine the association of these variants with prostate cancer risk, plasma hormone levels and androgenetic alopecia. Subjects include 827 cases and 736 controls from an Australian population-based case-control study of prostate cancer. Information on prostate cancer risk factors and patterns of balding were collected. Plasma levels of testosterone, 3a-diol glucuronide (3α-diolG), dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and estradiol were measured for controls. No associations with the V89L polymorphism were found. Carriers of the rarer A49T A allele were at a 60% higher risk of prostate cancer (OR = 1.60; 95% CI 1.09-2.36; p = 0.02) and 50% lower risk of vertex and frontal balding (p = 0.03) compared with men homozygous for the more common G allele. Although we found little evidence of association between this variant and plasma levels of 5 measured androgens, circulating 3a-diolG levels were 34% lower in A49T A allele carriers (p < 0.0001). Our study provides evidence that the SRD5A2 A49T A variant is associated with an increased risk of prostate cancer, lower levels of circulating 3a-diolG and decreased risk of baldness. These findings raise important questions with respect to previous assumptions concerning hormonal influences on prostate cancer risk in ageing males.</s0></fC01><fC02 i1="01" i2="X"><s0>002B04</s0></fC02><fC02 i1="02" i2="X"><s0>002B14D02</s0></fC02><fC02 i1="03" i2="X"><s0>235</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Cancer prostate</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Prostate cancer</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Cáncer de la próstata</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>3-Oxo-5α-steroid 4-dehydrogenase</s0><s2>FE</s2><s5>02</s5><s6>«3»-Oxo-«5α»-steroid «4»-dehydrogenase</s6></fC03><fC03 i1="02" i2="X" l="ENG"><s0>3-Oxo-5α-steroid 4-dehydrogenase</s0><s2>FE</s2><s5>02</s5><s6>«3»-Oxo-«5α»-steroid «4»-dehydrogenase</s6></fC03><fC03 i1="02" i2="X" l="SPA"><s0>3-Oxo-5α-steroid 4-dehydrogenase</s0><s2>FE</s2><s5>02</s5><s6>«3»-Oxo-«5α»-steroid «4»-dehydrogenase</s6></fC03><fC03 i1="03" i2="X" 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pathologie</s0><s5>41</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Prostate disease</s0><s5>41</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Prostata patología</s0><s5>41</s5></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Peau pathologie</s0><s5>42</s5></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Skin disease</s0><s5>42</s5></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Piel patología</s0><s5>42</s5></fC07><fC07 i1="10" i2="X" l="FRE"><s0>Génétique</s0><s5>43</s5></fC07><fC07 i1="10" i2="X" l="ENG"><s0>Genetics</s0><s5>43</s5></fC07><fC07 i1="10" i2="X" l="SPA"><s0>Genética</s0><s5>43</s5></fC07><fC07 i1="11" i2="X" l="FRE"><s0>Santé publique</s0><s5>45</s5></fC07><fC07 i1="11" i2="X" l="ENG"><s0>Public health</s0><s5>45</s5></fC07><fC07 i1="11" i2="X" l="SPA"><s0>Salud pública</s0><s5>45</s5></fC07><fN21><s1>085</s1></fN21></pA></standard></inist><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Nouvelle-Galles du Sud</li><li>Rhône-Alpes</li><li>Victoria (État)</li></region><settlement><li>Lyon</li><li>Melbourne</li><li>Sydney</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Hayes, Vanessa M" sort="Hayes, Vanessa M" uniqKey="Hayes V" first="Vanessa M." last="Hayes">Vanessa M. Hayes</name></region><name sortKey="English, Dallas R" sort="English, Dallas R" uniqKey="English D" first="Dallas R." last="English">Dallas R. English</name><name sortKey="English, Dallas R" sort="English, Dallas R" uniqKey="English D" first="Dallas R." last="English">Dallas R. English</name><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><name sortKey="Hayes, Vanessa M" sort="Hayes, Vanessa M" uniqKey="Hayes V" first="Vanessa M." last="Hayes">Vanessa M. Hayes</name><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><name sortKey="Morris, Howard A" sort="Morris, Howard A" uniqKey="Morris H" first="Howard A." last="Morris">Howard A. Morris</name><name sortKey="Padilla, Emma J D" sort="Padilla, Emma J D" uniqKey="Padilla E" first="Emma J. D." last="Padilla">Emma J. D. Padilla</name><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><name sortKey="Sutherland, Robert L" sort="Sutherland, Robert L" uniqKey="Sutherland R" first="Robert L." last="Sutherland">Robert L. Sutherland</name><name sortKey="Sutherland, Robert L" sort="Sutherland, Robert L" uniqKey="Sutherland R" first="Robert L." last="Sutherland">Robert L. Sutherland</name><name sortKey="Tilley, Wayne D" sort="Tilley, Wayne D" uniqKey="Tilley W" first="Wayne D." last="Tilley">Wayne D. Tilley</name><name sortKey="Tilley, Wayne D" sort="Tilley, Wayne D" uniqKey="Tilley W" first="Wayne D." last="Tilley">Wayne D. Tilley</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name></region><name sortKey="Boyle, Peter" sort="Boyle, Peter" uniqKey="Boyle P" first="Peter" last="Boyle">Peter Boyle</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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