Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, California 94122, USA.
Cancer. 2013 May 1;119(9):1652-9. doi: 10.1002/cncr.27952. Epub 2013 Jan 29.
Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are related to an increased lifetime risk of developing breast and ovarian cancer. Although risk-reducing salpingo-oophorectomy reduces the risk of both cancers, loss of fertility is a major concern. A recent study suggested an association between BRCA1 mutation and occult primary ovarian insufficiency. The objective of the current study was to determine whether BRCA1/2 mutation carriers have an earlier onset of natural menopause compared with unaffected women.
White carriers of the BRCA1/2 gene (n = 382) were identified within the Breast Cancer Risk Program Registry at the University of California at San Francisco and compared with non-clinic-based white women in northern California (n = 765). The 2 groups were compared with regard to median age at the time of natural menopause before and after adjustment for known risk factors, and the role of smoking within each group was examined using the Kaplan-Meier approach for unadjusted analyses and Cox proportional hazards regression analyses for adjusted analyses.
The median age at the time of natural menopause in the BRCA1/2 carriers was significantly younger than among the unaffected sample (50 years vs 53 years; P < .001). The unadjusted hazard ratio for natural menopause when comparing BRCA1/2 carriers with unaffected women was 4.06 (95% confidence interval, 3.03-5.45) and was 3.98 (95% confidence interval, 2.87-5.53) after adjusting for smoking, parity, and oral contraceptive use. For BRCA1/2 carriers who were current heavy smokers (smoking ≥ 20 cigarettes/day), the median age at natural menopause was 46 years versus 49 years for nonsmokers (P = .027).
The BRCA1/2 mutation was associated with a significantly earlier age at natural menopause, and heavy smoking compounded this risk. Because the relationship between menopause and the end of natural fertility is considered to be fixed, these findings suggest the risk of earlier infertility among BRCA1/2 carriers.
BRCA1 和 BRCA2（BRCA1/2）种系突变与乳腺癌和卵巢癌终生风险增加相关。尽管降低风险的输卵管卵巢切除术降低了这两种癌症的风险，但丧失生育能力是一个主要关注点。最近的一项研究表明 BRCA1 突变与隐匿性原发性卵巢功能不全之间存在关联。本研究的目的是确定 BRCA1/2 突变携带者与未受影响的女性相比，是否更早出现自然绝经。
在加利福尼亚大学旧金山分校的乳腺癌风险计划注册处确定了 BRCA1/2 基因的白人携带者（n = 382），并与加利福尼亚州北部非诊所的白人女性（n = 765）进行了比较。在调整已知危险因素后，比较了 2 组自然绝经时的中位年龄，并使用未经调整分析的 Kaplan-Meier 方法和调整分析的 Cox 比例风险回归分析检查了每组内吸烟的作用。
BRCA1/2 携带者的自然绝经中位年龄明显早于未受影响的样本（50 岁比 53 岁；P <.001）。比较 BRCA1/2 携带者与未受影响女性的自然绝经未调整风险比为 4.06（95%置信区间，3.03-5.45），调整吸烟、产次和口服避孕药使用后为 3.98（95%置信区间，2.87-5.53）。对于当前重度吸烟者（每天吸烟≥20 支）的 BRCA1/2 携带者，其自然绝经的中位年龄为 46 岁，而非吸烟者为 49 岁（P =.027）。
BRCA1/2 突变与自然绝经年龄明显提前相关，重度吸烟使这种风险增加。由于绝经与自然生育能力结束之间的关系被认为是固定的，这些发现表明 BRCA1/2 携带者更早出现不孕的风险。
