McLaughlin John R, Risch Harvey A, Lubinski Jan, Moller Pal, Ghadirian Parviz, Lynch Henry, Karlan Beth, Fishman David, Rosen Barry, Neuhausen Susan L, Offit Kenneth, Kauff Noah, Domchek Susan, Tung Nadine, Friedman Eitan, Foulkes William, Sun Ping, Narod Steven A
Samuel Lunenfeld Research Institute, Toronto, ON, Canada.
Lancet Oncol. 2007 Jan;8(1):26-34. doi: 10.1016/S1470-2045(06)70983-4.
Several of the known risk factors for ovarian cancer are thought to act through their effects on ovulation and the menstrual cycle, such as parity, breastfeeding, and use of oral contraceptives. We aimed to assess the effect of these three risk factors, and of tubal ligation, on the risk of ovarian cancer in women who carry a mutation in the BRCA1 or BRCA2 genes.
We did a matched case-control study in women who were found to carry a pathogenetic mutation in BRCA1 or BRCA2. Participants were derived from a population-based study of ovarian cancer in Ontario, Canada, and from an international registry of mutation carriers based in Toronto, ON, Canada. All participants completed a written questionnaire that detailed their reproductive history. Women with invasive ovarian cancer and controls were matched on year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of breast cancer. The odds ratios and 95% CI for ovarian cancer were estimated with respect to use of oral contraceptives, parity, breastfeeding, and tubal ligation.
Questionnaires were completed by 799 women with a history of invasive ovarian cancer (670 with BRCA1 mutations, 128 with BRCA2 mutations, and one with a mutation in both genes), and controls were 2424 women without ovarian cancer (2043 with BRCA1 mutations, 380 with BRCA2 mutations, and one with a mutation in both genes). Use of oral contraceptives reduced the risk of ovarian cancer in carriers of BRCA1 mutations (odds ratio 0.56 [95% CI 0.45-0.71]; p<0.0001) and carriers of BRCA2 mutations (0.39 [0.23-0.66]; p=0.0004). Parity was associated with a reduced risk for carriers of BRCA1 mutations (0.67 [0.46-0.96]; p=0.03), but with an increased risk for those with BRCA2 mutations (2.74 [1.18-6.41]; p=0.02). Breastfeeding was associated with a reduced risk for carriers of BRCA1 mutations (0.74 [0.56-0.97]; p=0.03). An effect of similar magnitude was seen for carriers of BRCA2 mutations (0.72 [0.41-1.29]; p=0.27), but this was not statistically significant. The association with tubal ligation was not significant for carriers of BRCA1 mutations (0.80 [0.59-1.08]; p=0.15), or for carriers of BRCA2 mutations (0.63 [0.34-1.15]; p=0.13).
Oral contraceptives could be used as a means to prevent ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The possible adverse effect of parity on ovarian-cancer risk in women with a BRCA2 mutation needs further study.
卵巢癌的一些已知风险因素被认为是通过对排卵和月经周期的影响而起作用的，如生育次数、母乳喂养及口服避孕药的使用。我们旨在评估这三个风险因素以及输卵管结扎对携带BRCA1或BRCA2基因的女性患卵巢癌风险的影响。
我们对被发现携带BRCA1或BRCA2致病突变的女性进行了一项匹配病例对照研究。参与者来自加拿大安大略省一项基于人群的卵巢癌研究以及位于加拿大安大略省多伦多市的一个国际突变携带者登记处。所有参与者都填写了一份详细记录其生殖史的书面问卷。患有浸润性卵巢癌的女性与对照者在出生年份、居住国家、突变类型（BRCA1或BRCA2）及乳腺癌病史方面进行匹配。就口服避孕药的使用、生育次数、母乳喂养及输卵管结扎情况，对卵巢癌的比值比及95%可信区间进行了估计。
799例有浸润性卵巢癌病史的女性（670例携带BRCA1突变，128例携带BRCA2突变，1例同时携带两种基因的突变）完成了问卷，对照者为2424例无卵巢癌的女性（2043例携带BRCA1突变，380例携带BRCA2突变，1例同时携带两种基因的突变）。口服避孕药可降低携带BRCA1突变者患卵巢癌的风险（比值比0.56 [95%可信区间0.45 - 0.71]；p<0.0001）以及携带BRCA2突变者患卵巢癌的风险（0.39 [0.23 - 0.66]；p = 0.0004）。生育次数与携带BRCA1突变者患卵巢癌风险降低相关（[0.67 [0.46 - 0.96]；p = 0.03），但与携带BRCA2突变者患卵巢癌风险增加相关（2.74 [1.18 - 6.41]；p = 0.02）。母乳喂养与携带BRCA1突变者患卵巢癌风险降低相关（0.74 [0.56 - 0.97]；p = 0.03）。携带BRCA2突变者也观察到了相似程度的影响（0.72 [0.41 - 1.29]；p = 0.27），但无统计学意义。对于携带BRCA1突变者（0.80 [0.59 - 1.08]；p = 0.15）或携带BRCA2突变者（0.63 [0.34 - 1.15]；p = 0.13），输卵管结扎与患卵巢癌风险的关联均不显著。
口服避孕药可作为预防携带BRCA1和BRCA2突变者患卵巢癌的一种手段。生育次数对携带BRCA2突变女性患卵巢癌风险可能的不良影响需要进一步研究。
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