Susanne-Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Genetics, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel.
Breast Cancer Res Treat. 2011 Sep;129(2):557-63. doi: 10.1007/s10549-011-1509-z. Epub 2011 Apr 16.
BRCA1 and BRCA2 germline mutations substantially increase breast and ovarian cancer risk, yet penetrance is incomplete. The effects of oral contraceptives (OC) on breast cancer risk in mutation carriers are unclear, and the putative effect of parental origin of mutation on cancer risk has not been reported. Data on OC use and parental origin of the mutation were obtained at counseling from 888 BRCA1 (n = 638) or BRCA2 (n = 250) Jewish Israeli mutation carriers who were counseled and genotyped in a single medical center. Overall, 403 (45.4%) of participants had breast cancer (age at diagnosis 49.65 ± 12.2 years), 112 (12.6%) ovarian cancer (age at diagnosis 56.8 ± 10.8 years) and the rest (n = 373-42%) were asymptomatic carriers (age at counseling 40.7 ± 10.6 years). Of study participants, 472 (53.15%) ever used OC, and 298 used OC for at least 5 years. In 129 the mutation originated on the paternal side as judged by direct testing or obligate carriership and in 460 the mutation was maternally inherited. Multivariate logistic regression analysis, and stratifying for birth year, age at menarche, breast feeding, and number of births, showed that ever use of OC (Hazards Ratio-HR = 1.84 95% CI 1.465-2.314, P = 0.001) and paternal compared with maternal origin of mutation (OR = 1.55 95% CI 1.14-2.12, P = 0.006) were significantly associated with breast cancer and an earlier age at breast cancer diagnosis. The authors conclude that OC use and paternal origin of mutation affect breast cancer penetrance in Jewish BRCA1 and BRCA2 mutation carriers.
BRCA1 和 BRCA2 种系突变显著增加乳腺癌和卵巢癌的风险，但外显率并不完全。口服避孕药（OC）对突变携带者乳腺癌风险的影响尚不清楚，且突变的亲本来源对癌症风险的潜在影响尚未报道。在一家医疗中心进行咨询和基因分型时，对 888 名 BRCA1（n=638）或 BRCA2（n=250）犹太以色列突变携带者进行了 OC 使用和突变亲本来源的数据收集。总体而言，403 名参与者（45.4%）患有乳腺癌（诊断时的年龄为 49.65±12.2 岁），112 名参与者（12.6%）患有卵巢癌（诊断时的年龄为 56.8±10.8 岁），其余（n=373-42%）为无症状携带者（咨询时的年龄为 40.7±10.6 岁）。在研究参与者中，472 名（53.15%）曾使用 OC，298 名至少使用 5 年 OC。根据直接检测或强制性携带者状态，129 名突变源自父系，而 460 名突变源自母系遗传。多变量逻辑回归分析，并按出生年份、初潮年龄、母乳喂养和生育次数进行分层，结果显示，OC 的使用（危害比 HR=1.84 95%置信区间 1.465-2.314，P=0.001）和与突变的母系来源相比来自父系的突变（比值比 OR=1.55 95%置信区间 1.14-2.12，P=0.006）与乳腺癌和更早的乳腺癌诊断年龄显著相关。作者得出结论，OC 使用和突变的父系来源影响犹太 BRCA1 和 BRCA2 突变携带者的乳腺癌外显率。
