CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer

Endocrine-Related Cancer

Volumn 23, Issue 2, 2016, Pages 77-91

  Thompson, Deborah J ^a   O'Mara, Tracy A ^b   Glubb, Dylan M ^b   Painter, Jodie N ^b   Cheng, Timothy ^c   Folkerd, Elizabeth ^d   Doody, Deborah ^d   Dennis, Joe ^a   Webb, Penelope M ^b   Gorman, Maggie ^b   Martin, Lynn ^c   Hodgson, Shirley ^e   Michailidou, Kyriaki ^a   Tyrer, Jonathan P ^f   Maranian, Mel J ^f   Hall, Per ^g   Czene, Kamila ^g   Darabi, Hatef ^g   Li, Jingmei ^g   Fasching, Peter A ^h,i   Hein, Alexander ⁱ   Beckmann, Matthias W ⁱ   Ekici, Arif B ⁱ   Dörk, Thilo ^j   Hillemanns, Peter ^j   Dürst, Matthias ^k   Runnebaum, Ingo ^k   Zhao, Hui ^l,m   Depreeuw, Jeroen ^l,m   Schrauwen, Stefanie ^m   Amant, Frederic ^m   Goode, Ellen L ⁿ   Fridley, Brooke L ^o   Dowdy, Sean C ⁿ   Winham, Stacey J ⁿ   Salvesen, Helga B ^p,q   Trovik, Jone ^p,q   Tormund, Njolstad S ^p,q   Werner, Henrica M J ^p,q   Ashton, Katie ^r,s,t   Proietto, Tony ^u   Otton, Geoffrey ^u   Carvajal Carmona, Luis ^v,w   Tham, Emma ^g   Liu, Tao ^g   Mints, Miriam ^g,x   Scott, Rodney J ^r,s,t,y   McEvoy, Mark ^u   Attia, John ^r,u   Holliday, Elizabeth G ^r,u   Montgomery, Grant W ^b   Martin, Nicholas G ^b   Nyholt, Dale R ^b,z   Henders, Anjali K ^b   Hopper, John L ^aa   Traficante, Nadia ^ab   Ruebner, Matthias ⁱ   Swerdlow, Anthony J ^ac   Burwinkel, Barbara ^ad,ae   Brenner, Hermann ^ae   Meindl, Alfons ^af   Brauch, Hiltrud ^ae,ag,ah   Lindblom, Annika ^g   Lambrechts, Diether ^l,m   Chang Claude, Jenny ^ae   Couch, Fergus J ⁿ   Giles, Graham G ^aa,ai,aj   Kristensen, Vessela N ^ak,al,am   Cox, Angela ^an   Bolla, Manjeet K ^a   Wang, Qin ^a   Bojesen, Stig E ^ao,ap   Shah, Mitul ^f   Luben, Robert ^f   Khaw, Kay Tee ^f   Pharoah, Paul D P ^f   Dunning, Alison M ^f   Tomlinson, Ian ^c   Dowsett, Mitch ^d   Easton, Douglas F ^a,f   Spurdle, Amanda B ^b   more..

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d ROYAL MARSDEN HOSPITAL   (United Kingdom)

^e ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^g KAROLINSKA INSTITUTE   (Sweden)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^j HANNOVER MEDICAL SCHOOL   (Germany)

^k JENA UNIVERSITY HOSPITAL   (Germany)

^l Vesalius Research Center   (Belgium)

^m UNIVERSITY HOSPITALS LEUVEN   (Belgium)

ⁿ MAYO CLINIC   (United States)

^o UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^p UNIVERSITY OF BERGEN   (Norway)

^q HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^r JOHN HUNTER HOSPITAL   (Australia)

^s UNIVERSITY OF NEWCASTLE   (Australia)

^t UNIVERSITY OF NEWCASTLE   (Australia)

^u UNIVERSITY OF NEWCASTLE   (Australia)

^v UNIVERSIDAD DEL TOLIMA   (Colombia)

^w UNIVERSITY OF CALIFORNIA   (United States)

^x KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^y JOHN HUNTER HOSPITAL   (Australia)

^z QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^aa UNIVERSITY OF MELBOURNE   (Australia)

^ab UNIVERSITY OF MELBOURNE   (Australia)

^ac INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^ad UNIVERSITY OF HEIDELBERG   (Germany)

^ae GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^af TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^ag DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^ah UNIVERSITY OF TÜBINGEN   (Germany)

^ai CANCER EPIDEMIOLOGY CENTRE   (Australia)

^aj MONASH UNIVERSITY   (Australia)

^ak OSLO UNIVERSITY HOSPITAL   (Norway)

^al UNIVERSITY OF OSLO   (Norway)

^am AKERSHUS UNIVERSITY HOSPITAL   (Norway)

^an UNIVERSITY OF SHEFFIELD   (United Kingdom)

^ao UNIVERSITY OF COPENHAGEN   (Denmark)

^ap GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

more..

Author keywords

CYP19A1; Endometrial cancer; Estradiol

Indexed keywords

AROMATASE; ESTRADIOL; CYP19A1 PROTEIN, HUMAN;

ARTICLE; CANCER RISK; CASE CONTROL STUDY; CONTROLLED STUDY; ENDOMETRIUM CANCER; FEMALE; GENE MAPPING; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE ENVIRONMENT INTERACTION; HORMONE DETERMINATION; HUMAN; INFORMATION RETRIEVAL; MAJOR CLINICAL STUDY; MENDELIAN RANDOMIZATION ANALYSIS; PHENOTYPE; POSTMENOPAUSE; RISK ASSESSMENT; SINGLE NUCLEOTIDE POLYMORPHISM; AGE; ALLELE; BLOOD; BODY MASS; ENDOMETRIAL NEOPLASMS; GENETIC ASSOCIATION STUDY; GENETIC PREDISPOSITION; GENETICS; GENOTYPE; PATHOLOGY;

AGE FACTORS; ALLELES; AROMATASE; BODY MASS INDEX; CASE-CONTROL STUDIES; ENDOMETRIAL NEOPLASMS; ESTRADIOL; FEMALE; GENE-ENVIRONMENT INTERACTION; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84956730658     PISSN: 13510088     EISSN: 14796821     Source Type: Journal    
DOI: 10.1530/ERC-15-0386     Document Type: Article

References (49)

1. Ahn J, Schumacher FR, Berndt SI, Pfeiffer R, Albanes D, Andriole GL, Ardanaz E, Boeing H, Bueno-de-Mesquita B & Chanock SJ 2009 Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). Human Molecular Genetics 18 3749-3757. (doi:10.1093/hmg/ ddp302)
2. Allen NE, Key TJ, Dossus L, Rinaldi S, Cust A, Lukanova A, Peeters PH, Onland-Moret NC, Lahmann PH, Berrino F et al. 2008 Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocrine-Related Cancer 15 485-497. (doi:10.1677/ERC-07-0064)
3. Aulchenko YS, Struchalin MV & van Duijn CM 2010 ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics 11 134. (doi:10.1186/1471-2105-11-134)
4. Beckmann L, Husing A, Setiawan VW, Amiano P, Clavel-Chapelon F, Chanock SJ, Cox DG, Diver R, Dossus L, Feigelson HS et al. 2011 Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the breast and prostate cancer cohort consortium (BPC3). Journal of Clinical Endocrinology and Metabolism 96 E360-E367. (doi:10.1210/jc.2010-0912)
5. Beral V, Bull D & Reeves G & Million Women Study Collaborators 2005 Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 365 1543-1551. (doi:10.1016/S0140- 6736(05)66455-0)
6. Chen WM & Abecasis GR 2007 Family-based association tests for genomewide association scans. American Journal of Human Genetics 81 913-926. (doi:10.1086/521580)
7. Cleland WH, Mendelson CR & Simpson ER 1985 Effects of aging and obesity on aromatase activity of human adipose cells. Journal of Clinical Endocrinology and Metabolism 60 174-177. (doi:10.1210/jcem-60-1-174)
8. C-Reactive Protein Coronary Heart Disease Genetics Collaboration, Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T, Engert JC, Clarke R & Davey-Smith G 2011 Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data. British Medical Journal 342 d548. (doi:10.1136/bmj.d548)
9. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S & Boyle P 2003 Overview of the main outcomes in breast-cancer prevention trials. Lancet 361 296-300. (doi:10.1016/S0140-6736(03)12342-2)
10. Day N, Oakes S, Luben R, Khaw KT, Bingham S, Welch A & Wareham N 1999 EPIC-Norfolk: Study design and characteristics of the cohort. European Prospective Investigation of Cancer. British Journal of Cancer 80 (Suppl 1) 95-103.
11. Dowsett M, Goss PE, Powles TJ, Hutchinson G, Brodie AM, Jeffcoate SL & Coombes RC 1987 Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: Optimization of therapeutic dose and route. Cancer Research 47 1957-1961.
12. Dunning AM, Dowsett M, Healey CS, Tee L, Luben RN, Folkerd E, Novik KL, Kelemen L, Ogata S, Pharoah PD et al. 2004 Polymorphisms associated with circulating sex hormone levels in postmenopausal women. Journal of the National Cancer Institute 96 936-945. (doi:10.1093/jnci/ djh167)
13. Eeckhoute J, Carroll JS, Geistlinger TR, Torres-Arzayus MI & Brown M 2006 A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer. Genes and Development 20 2513-2526. (doi:10.1101/gad.1446006)
14. Eriksson AL, Lorentzon M, Vandenput L, Labrie F, Lindersson M, Syvanen AC, Orwoll ES, Cummings SR, Zmuda JM, Ljunggren O et al. 2009 Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men. Journal of Clinical Endocrinology and Metabolism 94 1033-1041. (doi:10.1210/jc.2008-1283)
15. Ferreira T & Marchini J 2011 Modeling interactions with known risk loci-A Bayesian model averaging approach. Annals of Human Genetics 75 1-9. (doi:10.1111/j.1469-1809.2010.00618.x)
16. Flote VG, Furberg A, McTiernan A, Frydenberg H, Ursin G, Iversen A, Lofteroed T, Ellison PT, Wist EA, Egeland T et al. 2014 Gene variations in oestrogen pathways, CYP19A1, daily 17ss-E2 and mammographic density phenotypes in premenopausal women. Breast Cancer Research 16 499. (doi:10.1186/s13058-014-0499-2)
17. Haiman CA, Dossus L, Setiawan VW, Stram DO, Dunning AM, Thomas G, Thun MJ, Albanes D, Altshuler D, Ardanaz E et al. 2007 Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women. Cancer Research 67 1893-1897. (doi:10.1158/0008-5472.CAN-06-4123)
18. Higgins JP & Thompson SG 2002 Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 21 1539-1558. (doi:10.1002/ sim.1186)
19. Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, Spain SL, Broderick P, Domingo E, Farrington S et al. 2010 Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nature Genetics 42 973-977. (doi:10.1038/ng.670)
20. Howie BN, Donnelly P & Marchini J 2009 A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genetics 5 e1000529. (doi:10.1371/journal.pgen. 1000529)
21. Howie B, Marchini J & Stephens M 2011 Genotype imputation with thousands of genomes. G3 1 457-470. (doi:10.1534/g3.111.001198)
22. Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium 2012 The interleukin-6 receptor as a target for prevention of coronary heart disease: A mendelian randomisation analysis. Lancet 379 1214-1224. (doi:10.1016/S0140-6736(12)60110-X)
23. International Agency for Research on Cancer (IARC) Working Group on the Evaluation of Cancer-Preventive Strategies 2002 Weight control and physical activity. pp 1-315. Lyon, France: IARC Press.
24. Key TJ & Pike MC 1988 The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: Its central role in explaining and predicting endometrial cancer risk. British Journal of Cancer 57 205-212. (doi:10.1038/bjc.1988.44)
25. Key T, Appleby P, Barnes I, Reeves G & Endogenous Hormones and Breast Cancer Collaborative Group 2002 Endogenous sex hormones and breast cancer in postmenopausal women: Reanalysis of nine prospective studies. Journal of the National Cancer Institute 94 606-616. (doi:10.1093/jnci/94.8.606)
26. Kidokoro K, Ino K, Hirose K, Kajiyama H, Hosono S, Suzuki T, Kawase T, Hiraki A, Hamajima N, Tanaka H et al. 2009 Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women. Journal of Human Genetics 54 78-85. (doi:10.1038/jhg. 2008.11)
27. Lee SU & Maeda T 2012 POK/ZBTB proteins: An emerging family of proteins that regulate lymphoid development and function. Immunological Reviews 247 107-119. (doi:10.1111/j.1600-065X.2012.01116.x)
28. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J et al. 2015 Genetic studies of body mass index yield new insights for obesity biology. Nature 518 197-206. (doi:10.1038/nature14177)
29. Low YL, Li Y, Humphreys K, Thalamuthu A, Li Y, Darabi H, Wedren S, Bonnard C, Czene K, Iles MM et al. 2010 Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility. PLoS Genetics 6 e1001012. (doi:10.1371/journal. pgen.1001012)
30. Lukanova A, Lundin E, Micheli A, Arslan A, Ferrari P, Rinaldi S, Krogh V, Lenner P, Shore RE, Biessy C et al. 2004 Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. International Journal of Cancer 108 425-432. (doi:10.1002/ijc.11529)
31. Lundin E, Wirgin I, Lukanova A, Afanasyeva Y, Krogh V, Axelsson T, Hemminki K, Clendenen TV, Arslan AA, Ohlson N et al. 2012 Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer. Cancer Epidemiology 36 445-452. (doi:10.1016/j.canep.2012.04.006)
32. McEvoy M, Smith W, D'Este C, Duke J, Peel R, Schofield P, Scott R, Byles J, Henry D, Ewald B et al. 2010 Cohort profile: The hunter community study. International Journal of Epidemiology 39 1452-1463. (doi:10.1093/ ije/dyp343)
33. McGregor B, Pfitzner J, Zhu G, Grace M, Eldridge A, Pearson J, Mayne C, Aitken JF, Green AC & Martin NG 1999 Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins. Genetic Epidemiology 16 40-53. (doi:10.1002/(SICI)1098-2272(1999)16:1!40::AID-GEPI4O 3.0.CO;2-1)
34. Michailidou K, Hall P, Gonzalez-Neira A, GhoussainiM, Dennis J,Milne RL, Schmidt MK, Chang-Claude J, Bojesen SE & Bolla MK 2013 Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nature Genetics 45 353-361, 361e351-352. (doi:10.1038/ng.2563)
35. Painter JN, Anderson CA, Nyholt DR, Macgregor S, Lin J, Lee SH, Lambert A, Zhao ZZ, Roseman F, Guo Q et al. 2011 Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nature Genetics 43 51-54. (doi:10.1038/ng.731)
36. Painter JN, O'Mara TA, Batra J, Cheng T, Lose FA, Dennis J, Michailidou K, Tyrer JP, Ahmed S, Ferguson K et al. 2015 Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk. Human Molecular Genetics 24 1478-1492. (doi:10.1093/hmg/ddu552)
37. Paynter RA, Hankinson SE, Colditz GA, Kraft P, Hunter DJ & De Vivo I 2005 CYP19 (aromatase) haplotypes and endometrial cancer risk. International Journal of Cancer 116 267-274. (doi:10.1002/ijc.21041)
38. Pharoah PD, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, Buckley M, Fridley BL, Tyrer JP & Shen H 2013 GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nature Genetics 45 362-370, 370e361-362. (doi:10.1038/ng.2564)
39. Prescott J, Thompson DJ, Kraft P, Chanock SJ, Audley T, Brown J, Leyland J, Folkerd E, Doody D, Hankinson SE et al. 2012 Genome-wide association study of circulating E2, T, and sex hormone-binding globulin in postmenopausal women. PLoS ONE 7 e37815. (doi:10.1371/journal. pone.0037815)
40. Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR & Willer CJ 2010 LocusZoom: Regional visualization of genome-wide association scan results. Bioinformatics 26 2336-2337. (doi:10.1093/bioinformatics/btq419)
41. Setiawan VW, Doherty JA, Shu XO, Akbari MR, Chen C, De Vivo I, Demichele A, Garcia-Closas M, Goodman MT, Haiman CA et al. 2009 Two estrogen-related variants in CYP19A1 and endometrial cancer risk: A pooled analysis in the Epidemiology of Endometrial Cancer Consortium. Cancer Epidemiology, Biomarkers & Prevention 18 242-247. (doi:10.1158/1055-9965.EPI-08-0689)
42. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM et al. 2013 Type I and II endometrial cancers: Have they different risk factors? Journal of Clinical Oncology 31 2607-2618. (doi:10.1200/JCO.2012.48.2596)
43. Spurdle AB, Thompson DJ, Ahmed S, Ferguson K, Healey CS, O'Mara T, Walker LC, Montgomery SB, Dermitzakis ET, Australian National Endometrial Cancer Study G et al. 2011 Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nature Genetics 43 451-454. (doi:10.1038/ng.812)
44. TaoMH, Cai Q, Zhang ZF, Xu WH, Kataoka N, WenW, Xiang YB, ZhengW & Shu XO 2007 Polymorphisms in the CYP19A1 (aromatase) gene and endometrial cancer risk in Chinese women. Cancer Epidemiology, Biomarkers & Prevention 16 943-949. (doi:10.1158/1055-9965. EPI-06-1012)
45. Travis RC, Schumacher F, Hirschhorn JN, Kraft P, Allen NE, Albanes D, Berglund G, Berndt SI, Boeing H, Bueno-de-Mesquita HB et al. 2009 CYP19A1 genetic variation in relation to prostate cancer risk and circulating sex hormone concentrations in men from the Breast and Prostate Cancer Cohort Consortium. Cancer Epidemiology, Biomarkers & Prevention 18 2734-2744. (doi:10.1158/1055-9965.EPI-09-0496)
46. Udler MS, Tyrer J & Easton DF 2010 Evaluating the power to discriminate between highly correlated SNPs in genetic association studies. Genetic Epidemiology 34 463-468. (doi:10.1002/gepi.20504)
47. Varghese JS, Smith PL, Folkerd E, Brown J, Leyland J, Audley T, Warren RM, Dowsett M, Easton DF & Thompson DJ 2012 The heritability of mammographic breast density and circulating sex-hormone levels: Two independent breast cancer risk factors. Cancer Epidemiology, Biomarkers & Prevention 21 2167-2175. (doi:10.1158/1055-9965. EPI-12-0789)
48. Wellcome Trust Case Control Consortium 2007 Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447 661-678. (doi:10.1038/ nature05911)
49. Zeleniuch-Jacquotte A, Akhmedkhanov A, Kato I, Koenig KL, Shore RE, Kim MY, Levitz M, Mittal KR, Raju U, Banerjee S et al. 2001 Postmenopausal endogenous oestrogens and risk of endometrial cancer: Results of a prospective study. British Journal of Cancer 84 975-981. (doi:10.1054/bjoc.2001.1704)