Five Polymorphisms and Breast Cancer Risk: Results from the Breast Cancer Association Consortium
Authors: Gaudet Mia M. , Milne Roger L. , Cox Angela , Camp Nicola J. , Goode Ellen L. , Humphreys Manjeet K. , Dunning Alison M. , Morrison Jonathan , Giles Graham G. , Severi Gianluca , Baglietto Laura , English Dallas R. , Couch Fergus J. , Olson Janet E. , Wang Xianshu , Chang-Claude Jenny , Flesch-Janys Dieter , Abbas Sascha , Salazar Ramona , Mannermaa Arto , Kataja Vesa , Kosma Veli-Matti , Lindblom Annika , Margolin Sara , Heikkinen Tuomas , Kämpjärvi Kati , Aaltonen Kirsimari , Nevanlinna Heli , Bogdanova Natalia , Coinac Irina , Schürmann Peter , Dörk Thilo , Bartram Claus R. , Schmutzler Rita K. , Tchatchou Sandrine , Burwinkel Barbara , Brauch Hiltrud , Torres Diana , Hamann Ute , Justenhoven Christina , Ribas Gloria , Arias José I. , Benitez Javier , Bojesen Stig E. , Nordestgaard Børge G. , Flyger Henrik L. , Peto Julian , Fletcher Olivia , Johnson Nichola , dos Santos Silva Isabel , Fasching Peter A. , Beckmann Matthias W. , Strick Reiner , Ekici Arif B. , Broeks Annegien , Schmidt Marjanka K. , van Leeuwen Flora E. , Van't Veer Laura J. , Southey Melissa C. , Hopper John L. , Apicella Carmel , Haiman Christopher A. , Henderson Brian E. , Le Marchand Loic , Kolonel Laurence N. , Kristensen Vessela , Grenaker Alnæs Grethe , Hunter David J. , Kraft Peter , Cox David G. , Hankinson Susan E. , Seynaeve Caroline , Vreeswijk Maaike P.G. , Tollenaar Rob A.E.M. , Devilee Peter , Chanock Stephen , Lissowska Jolanta , Brinton Louise , Peplonska Beata , Czene Kamila , Hall Per , Li Yuqing , Liu Jianjun , Balasubramanian Sabapathy , Rafii Saeed , Reed Malcolm W.R. , Pooley Karen A. , Conroy Don , Baynes Caroline , Kang Daehee , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Shen Chen-Yang , Wang Hui-Chun , Yu Jyh-Cherng , Wu Pei-Ei , Anton-Culver Hoda , Ziogoas Argyrios , Egan Kathleen , Newcomb Polly , Titus-Ernstoff Linda , Trentham Dietz Amy , Sigurdson Alice J. , Alexander Bruce H. , Bhatti Parveen , Allen-Brady Kristina , Cannon-Albright Lisa A. , Wong Jathine ,   Australian Ovarian Cancer Study Group, Chenevix-Trench Georgia , Spurdle Amanda B. , Beesley Jonathan , Pharoah Paul D.P. , Easton Doug F. , Garcia-Closas Montserrat ,   on behalf of the Breast Cancer Association Consortium
Published: May 2009

Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610–6)