影响BRCA1和BRCA2突变携带者排卵及卵巢癌风险的因素。
Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
作者信息
Kotsopoulos Joanne, Lubinski Jan, Gronwald Jacek, Cybulski Cezary, Demsky Rochelle, Neuhausen Susan L, Kim-Sing Charmaine, Tung Nadine, Friedman Susan, Senter Leigha, Weitzel Jeffrey, Karlan Beth, Moller Pal, Sun Ping, Narod Steven A
机构信息
Familial Breast Cancer Unit, Women's College Research Institute, Toronto, ON, Canada.
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
出版信息
Int J Cancer. 2015 Sep 1;137(5):1136-46. doi: 10.1002/ijc.29386. Epub 2014 Dec 18.
The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.
排卵周期的终生次数在与BRCA相关的卵巢癌背景下尚未得到评估。因此,我们开展了一项匹配病例对照研究,以评估排卵周期的累积次数(及其构成因素)与BRCA突变携带者患卵巢癌风险之间的关系(1329例病例和5267例对照)。有关生殖和激素因素的信息通过常规发放的问卷收集。采用条件逻辑回归评估所有关联。我们观察到,排卵周期处于最低四分位数与最高四分位数的女性相比,患卵巢癌的风险降低了45%(OR = 0.55;95% CI 0.41 - 0.75,p = 0.0001)。母乳喂养超过12个月分别使BRCA1和BRCA2突变携带者的风险降低38%(95% CI 0.48 - 0.79)和50%(95% CI 0.29 - 0.84)。对于口服避孕药的使用,BRCA1突变携带者使用五年或更长时间获益最大(OR = 0.50;95% CI 0.40 - 0.63),BRCA2突变携带者使用三年或更长时间获益最大(OR = 0.42;95% CI 0.22 - 0.83)。生育次数增加在BRCA1突变携带者中呈现显著的负相关趋势(OR = 0.87;95% CI 0.79 - 0.96;p趋势 = 0.005),但在BRCA2突变携带者中未观察到(OR 0.98;95% CI 0.81 - 1.19;p趋势 = 0.85)。绝经年龄较晚与BRCA1突变女性的风险增加相关(OR趋势 = 1.18;95% CI 1.03 - 1.35;p = 0.02)。这些发现支持母乳喂养和口服避孕药在携带BRCA突变女性卵巢癌一级预防中发挥重要作用。
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本文引用的文献
J Natl Cancer Inst. 2014-6
Int J Womens Health. 2014-1-28
Breast Cancer Res Treat. 2014-1-24
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BMC Med Res Methodol. 2012-11-23
Hematol Oncol Clin North Am. 2011-11-25