Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

被引：13

作者：

Johnson, Nichola ^{[1
,2
]}

Dudbridge, Frank ^{[3
]}

Orr, Nick ^{[1
,2
]}

Gibson, Lorna ^{[3
]}

Jones, Michael E. ^{[4
]}

Schoemaker, Minouk J. ^{[4
]}

Folkerd, Elizabeth J. ^{[5
]}

Haynes, Ben P. ^{[5
]}

Hopper, John L. ^{[6
]}

Southey, Melissa C. ^{[7
]}

Dite, Gillian S. ^{[6
]}

Apicella, Carmel ^{[6
]}

Schmidt, Marjanka K. ^{[8
]}

Broeks, Annegien ^{[8
]}

Van't Veer, Laura J. ^{[8
]}

Atsma, Femke ^{[9
]}

Muir, Kenneth ^{[10
]}

Lophatananon, Artitaya ^{[10
]}

Fasching, Peter A. ^{[11
,12
]}

Beckmann, Matthias W. ^{[11
]}

Ekici, Arif B. ^{[13
]}

Renner, Stefan P. ^{[11
]}

Sawyer, Elinor ^{[14
]}

Tomlinson, Ian ^{[15
,16
]}

Kerin, Michael ^{[17
]}

Miller, Nicola ^{[17
]}

Burwinkel, Barbara ^{[18
,19
]}

Marme, Frederik ^{[18
]}

Schneeweiss, Andreas ^{[18
]}

Sohn, Christof ^{[18
,20
,21
]}

Guenel, Pascal ^{[22
,23
]}

Truong, Therese ^{[22
,23
]}

Cordina, Emilie ^{[22
,23
]}

Menegaux, Florence ^{[22
,23
]}

Bojesen, Stig E. ^{[24
,25
]}

Nordestgaard, Borge G. ^{[24
,25
]}

Flyger, Henrik ^{[26
]}

Milne, Roger ^{[27
]}

Zamora, M. Pilar ^{[28
]}

Arias Perez, Jose Ignacio ^{[29
]}

Benitez, Javier ^{[30
,31
]}

Bernstein, Leslie ^{[32
]}

Anton-Culver, Hoda ^{[33
]}

Ziogas, Argyrios ^{[33
]}

Dur, Christina Clarke ^{[34
]}

Brenner, Hermann ^{[35
,36
]}

Mueller, Heiko ^{[35
]}

Arndt, Volker ^{[35
]}

Dieffenbach, Aida Karina ^{[35
,36
]}

Meindl, Alfons ^{[37
]}

机构：

[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[2] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England

[3] London Sch Hyg & Trop Med, Non Commun Dis Epidemiol Dept, London WC1E 7HT, England

[4] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England

[5] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England

[6] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia

[7] Univ Melbourne, Dept Pathol, Genet Epidemiol Dept, Melbourne, Vic 3010, Australia

[8] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, NL-1066 CX Amsterdam, Netherlands

[9] Radboud Univ Nijmegen, Sanquin, NL-6525 GA Nijmegen, Netherlands

[10] Univ Warwick, Warwick Med Sch, Coventry CV4 7AJ, W Midlands, England

[11] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, D-91012 Erlangen, Germany

[12] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[13] Alexander Univ Erlangen, Inst Human Genet, D-91054 Erlangen, Germany

[14] Guys Hosp, NIHR Comprehens Biomed Res Ctr, Guys & St Thomas NHS Fdn Trust, Kings Coll London,Div Canc Studies, London SE1 9RT, England

[15] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[16] Univ Oxford, Oxford Biomed Res Ctr, Churchill Hosp, Oxford OX3 7LE, England

[17] Galway Univ Hosp, Inst Clin Sci, Galway, Ireland

[18] Natl Univ Ireland, Galway, Ireland

[19] Heidelberg Univ, Dept Obstet & Gynecol, D-69115 Heidelberg, Germany

[20] German Canc Res Ctr, Unit Mol Epidemiol C080, DKFZ, D-69120 Heidelberg, Germany

[21] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany

[22] INSERM, Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, U1018L, F-75654 Paris, France

[23] Univ Paris 11, UMRS 1018, F-75654 Paris, France

[24] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark

[25] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark

[26] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark

[27] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Genet & Mol Epidemiol Grp, Madrid 28029, Spain

[28] Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain

[29] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 107, Spain

[30] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid 28029, Spain

[31] Ctr Invest Red Enfermedades Raras CIBERER, Madrid 28029, Spain

[32] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA

[33] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92697 USA

[34] Canc Prevent Inst Calif, Fremont, CA 95438 USA

[35] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69121 Heidelberg, Germany

[36] German Canc Consortium DKTK, D-69121 Heidelberg, Germany

[37] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Clin Gynecol & Obstet, D-81675 Munich, Germany

[38] Heidelberg Univ, Inst Human Genet, D-69121 Heidelberg, Germany

[39] Univ Hosp Cologne, Ctr Mol Med Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, D-50931 Cologne, Germany

[40] Robert Bosch Stiftung GmbH, Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70184 Stuttgart, Germany

[41] Univ Tubingen, D-72074 Tubingen, Germany

[42] Evangel Kliniken Bonn GGmbH, Dept Internal Med, D-53113 Bonn, Germany

[43] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Obstet & Gynecol, FIN-00029 Helsinki, Finland

[44] Univ Helsinki, Cent Hosp, Dept Clin Genet, FIN-00029 Helsinki, Finland

[45] Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland

[46] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Chikusa Ku, Nagoya, Aichi 4648681, Japan

[47] Hannover Med Sch, Dept Obstet & Gynaecol, D-30625 Hannover, Germany

[48] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany

[49] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, BELARUS

[50] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

来源：

BREAST CANCER RESEARCH | 2014年 / 16卷 / 03期

关键词：

GENOME-WIDE ASSOCIATION; SEX-HORMONE LEVELS; PREMENOPAUSAL WOMEN; STEROID-HORMONES; SERUM; TWINS; ESTRADIOL;

D O I：

10.1186/bcr3662

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age <= 50 years. Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P-trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P-trend = 0.005) but not cases (P-trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P-het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age >= 15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P-trend = 0.002) but not for those who had their menarche age <= 11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P-trend = 0.29). Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

引用

页数：13

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