口服避孕药与BRCA1和BRCA2基因突变携带者患乳腺癌的风险
Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
作者信息
Narod Steven A, Dubé Marie-Pierre, Klijn Jan, Lubinski Jan, Lynch Henry T, Ghadirian Parviz, Provencher Diane, Heimdal Ketil, Moller Pal, Robson Mark, Offit Kenneth, Isaacs Claudine, Weber Barbara, Friedman Eitan, Gershoni-Baruch Ruth, Rennert Gad, Pasini Barbara, Wagner Theresa, Daly Mary, Garber Judy E, Neuhausen Susan L, Ainsworth Peter, Olsson Hakan, Evans Gareth, Osborne Michael, Couch Fergus, Foulkes William D, Warner Ellen, Kim-Sing Charmaine, Olopade Olufunmilayo, Tung Nadine, Saal Howard M, Weitzel Jeffrey, Merajver Sofia, Gauthier-Villars Marion, Jernstrom Helena, Sun Ping, Brunet Jean-Sebastien
机构信息
The Centre for Research on Women's Health, University of Toronto, 790 Bay Street, Toronto, Ontario M5G 1N8, Canada.
出版信息
J Natl Cancer Inst. 2002 Dec 4;94(23):1773-9. doi: 10.1093/jnci/94.23.1773.
BACKGROUND
Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2.
METHODS
We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided.
RESULTS
Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCA1 mutation carriers, ever use of oral contraceptives was associated with a modestly increased risk of breast cancer (OR = 1.20, 95% CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95% CI = 1.17 to 1.75).
CONCLUSIONS
Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.
背景
使用口服避孕药与年轻女性患乳腺癌风险增加有关。我们研究了在因携带两种乳腺癌易感基因（BRCA1和BRCA2）之一的突变而处于乳腺癌高风险的女性中是否也存在这种关联。
方法
我们对从11个国家的52个中心招募的1311对已知携带有害BRCA1和/或BRCA2突变的女性进行了一项匹配病例对照研究。被诊断患有乳腺癌的女性与对照者按出生年份、居住国、突变类型（BRCA1或BRCA2）以及卵巢癌病史进行匹配。所有研究对象均完成了一份关于口服避孕药使用情况的问卷。通过条件逻辑回归得出比值比（OR）和95%置信区间（CI）。所有统计检验均为双侧检验。
结果
在携带BRCA2突变的女性中，曾经使用口服避孕药与患乳腺癌风险增加无关（OR = 0.94，95%CI = 0.72至1.24）。对于携带BRCA1突变的女性，曾经使用口服避孕药与患乳腺癌风险适度增加有关（OR = 1.20，95%CI = 1.02至1.40）。然而，与从未使用过口服避孕药的BRCA1突变携带者相比，使用口服避孕药至少5年的携带者患乳腺癌风险增加（OR = 1.33，95%CI = 1.11至1.60），30岁之前使用口服避孕药的携带者也是如此（OR = 1.29，95%CI = 1.09至1.52），40岁之前被诊断患有乳腺癌的携带者同样如此（OR = 1.38，95%CI = 1.11至1.72），以及1975年之前首次使用口服避孕药的携带者（OR = 1.42，95%CI = 1.17至1.75）。
结论
在携带BRCA1突变的女性中，1975年之前首次使用口服避孕药、30岁之前使用口服避孕药或使用口服避孕药达5年及以上的女性可能患早发性乳腺癌的风险增加。口服避孕药似乎与携带BRCA2突变者患乳腺癌的风险无关，但针对携带BRCA2突变者的数据有限。
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