5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia
Identifieur interne : 009770 ( Main/Exploration ); précédent : 009769; suivant : 0097715α-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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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. 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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><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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