Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA).
Osorio A., Milne RL., Pita G., Peterlongo P., Heikkinen T., Simard J., Chenevix-Trench G., Spurdle AB., Beesley J., Chen X., Healey S., KConFab None., Neuhausen SL., Ding YC., Couch FJ., Wang X., Lindor N., Manoukian S., Barile M., Viel A., Tizzoni L., Szabo CI., Foretova L., Zikan M., Claes K., Greene MH., Mai P., Rennert G., Lejbkowicz F., Barnett-Griness O., Andrulis IL., Ozcelik H., Weerasooriya N., OCGN None., Gerdes A-M., Thomassen M., Cruger DG., Caligo MA., Friedman E., Kaufman B., Laitman Y., Cohen S., Kontorovich T., Gershoni-Baruch R., Dagan E., Jernström H., Askmalm MS., Arver B., Malmer B., SWE-BRCA None., Domchek SM., Nathanson KL., Brunet J., Ramón Y Cajal T., Yannoukakos D., Hamann U., HEBON None., Hogervorst FBL., Verhoef S., Gómez García EB., Wijnen JT., van den Ouweland A., EMBRACE None., Easton DF., Peock S., Cook M., Oliver CT., Frost D., Luccarini C., Evans DG., Lalloo F., Eeles R., Pichert G., Cook J., Hodgson S., Morrison PJ., Douglas F., Godwin AK., GEMO None., Sinilnikova OM., Barjhoux L., Stoppa-Lyonnet D., Moncoutier V., Giraud S., Cassini C., Olivier-Faivre L., Révillion F., Peyrat J-P., Muller D., Fricker J-P., Lynch HT., John EM., Buys S., Daly M., Hopper JL., Terry MB., Miron A., Yassin Y., Goldgar D., Breast Cancer Family Registry None., Singer CF., Gschwantler-Kaulich D., Pfeiler G., Spiess A-C., Hansen TVO., Johannsson OT., Kirchhoff T., Offit K., Kosarin K., Piedmonte M., Rodriguez GC., Wakeley K., Boggess JF., Basil J., Schwartz PE., Blank SV., Toland AE., Montagna M., Casella C., Imyanitov EN., Allavena A., Schmutzler RK., Versmold B., Engel C., Meindl A., Ditsch N., Arnold N., Niederacher D., Deissler H., Fiebig B., Varon-Mateeva R., Schaefer D., Froster UG., Caldes T., de la Hoya M., McGuffog L., Antoniou AC., Nevanlinna H., Radice P., Benítez J., CMBA None.
BackgroundIn this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers.MethodsWe have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach.ResultsWe found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers.ConclusionThis SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.