Segev Yakir, Rosen Barry, Lubinski Jan, Gronwald Jacek, Lynch Henry T, Moller Pal, Kim-Sing Charmaine, Ghadirian Parviz, Karlan Beth, Eng Charis, Gilchrist Dawna, Neuhausen Susan L, Eisen Andrea, Friedman Eitan, Euhus David, Ping Sun, Narod Steven A
Familial Breast Cancer Research, Women's College Research Institute, 790 Bay Street, 7th Floor, Toronto, ON, M5G 1N8, Canada.
Fam Cancer. 2015 Sep;14(3):383-91. doi: 10.1007/s10689-015-9798-8.
BRCA mutation carriers may use tamoxifen for breast cancer prevention or treatment. Hormone replacement therapy is often prescribed after surgical menopause and oral contraceptives are recommended for ovarian cancer prevention. The objective of this study was to assess the impact of these medications and other risk factors on endometrial cancer risk in BRCA carriers. Women with a BRCA1 or BRCA2 mutation were identified from a registry of mutation carriers. Cases were 83 women who had a diagnosis of endometrial cancer. Controls were 1027 matched women who did not develop endometrial cancer and who had an intact uterus. All women completed a baseline questionnaire, which included questions about ages at menarche and menopause, oral contraceptive use, hormone replacement therapy use, hysterectomy, oophorectomy, breast cancer history and tamoxifen use. We estimated the odds ratio associated with each risk factor in a multivariate analysis. No differences were found between cases and controls in terms of age at menarche, BMI, smoking, or oral contraceptive use. In a multivariate analysis, for women taking estrogen-only hormone replacement therapy, the odds ratio was 0.23 (95% CI 0.03-1.78, p = 0.16), and for women taking progesterone-only hormone replacement therapy the odds ratio was 6.91 (95% CI 0.99-98.1, p = 0.05). The adjusted odds ratio for endometrial cancer associated with a history of tamoxifen use was 3.50 (95% CI 1.51-8.10, p = 0.003). The observed increased risk of endometrial cancer associated with progesterone-only therapy merits further study.
携带BRCA基因突变者可使用他莫昔芬预防或治疗乳腺癌。手术绝经后常开具激素替代疗法，推荐使用口服避孕药预防卵巢癌。本研究的目的是评估这些药物及其他风险因素对携带BRCA基因者患子宫内膜癌风险的影响。从基因突变携带者登记处识别出携带BRCA1或BRCA2基因突变的女性。病例为83例诊断为子宫内膜癌的女性。对照为1027例未患子宫内膜癌且子宫完整的匹配女性。所有女性均完成了一份基线调查问卷，其中包括初潮和绝经年龄、口服避孕药使用情况、激素替代疗法使用情况、子宫切除术、卵巢切除术、乳腺癌病史及他莫昔芬使用情况等问题。我们在多变量分析中估计了与每个风险因素相关的比值比。在初潮年龄、体重指数、吸烟或口服避孕药使用方面，病例组和对照组之间未发现差异。在多变量分析中，仅服用雌激素的激素替代疗法女性的比值比为0.23（95%可信区间0.03 - 1.78，p = 0.16），仅服用孕激素的激素替代疗法女性的比值比为6.91（95%可信区间0.99 - 98.1，p = 0.05）。与他莫昔芬使用史相关的子宫内膜癌调整后比值比为3.50（95%可信区间1.51 - 8.10，p = 0.003）。观察到的仅使用孕激素疗法与子宫内膜癌风险增加相关，值得进一步研究。
