Familial clustering of site-specific cancer risks associated with BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population
Familial clustering of site-specific cancer risks associated with BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population
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DOI：
10.1073/pnas.0511301103
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发表时间：
2006-03-07
影响因子：
11.1
通讯作者：
Levy-Lahad, E
中科院分区：
文献类型：
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作者：
Simchoni, S;Friedman, E;Levy-Lahad, E
BRCA1和BRCA2的遗传突变会显著增加患乳腺癌和卵巢癌的风险。我们使用流行病学方法评估了具有BRCA1或BRCA2遗传突变的德系犹太血统女性患乳腺癌和卵巢癌的相对风险。在已知携带BRCA1或BRCA2突变的亲属中，一个家庭的指示病例(即乳腺癌与卵巢癌)的癌症与特定部位癌症的风险显著相关。乳腺癌指标病例亲属患乳腺癌的风险高于卵巢癌指标病例亲属[BRCA1携带者风险比(HR)=3.0P&t；0.001，BRCA2携带者风险比HR=4.8P=0.017]；卵巢癌指标病例亲属患卵巢癌风险高于乳腺癌指标病例亲属(HR=7.2P=0.001，BRCA2携带者HIR=15.8P=0.018)。乳腺癌和卵巢癌的风险也随着出生年份的增加而增加。出生后每十年，患病风险增加1.2倍(P=0.03)。指示病例的肿瘤部位和出生队列的影响是独立的。这些结果表明，遗传和非遗传因素都改变了BRCA1和BRCA2突变携带者的癌症风险，遗传修饰因素和其他家族性因素可能影响乳腺癌或卵巢癌的风险。
inherited mutations in BRCA1 and BRCA2 lead to significantly increased risks of breast and ovarian cancer. We used epidemiologic methods to evaluate the relative risks of breast cancer vs. ovarian cancer among women of Ashkenazi Jewish ancestry with inherited mutations in BRCA1 or BRCA2. The cancer of a family's index case (i.e., breast cancer vs. ovarian cancer) was significantly associated with site-specific risks of cancer in relatives known to carry mutations in BRCA1 or BRCA2. Specifically, breast cancer risks were higher among relatives of breast cancer index cases compared with relatives of ovarian cancer index cases [hazard ratio (HR) = 3.0, P < 0.001 for BRCA1 carriers and HR = 4.8, P = 0.017 for BRCA2 carriers], and ovarian cancer risks were higher among relatives of ovarian cancer index cases compared with relatives of breast cancer index cases (HR = 7.2, P = 0.001 for BRCA1 carriers and HIR = 15.8, P = 0.018 for BRCA2 carriers). Breast and ovarian cancer risks also increased with more recent year of birth. For each later decade of birth, risk increased 1.2-fold (P = 0.03). Effects of cancer site of the index case and of birth cohort were independent. These results suggest that both genetic and nongenetic factors modify cancer risks among BRCA1 and BRCA2 mutation carriers, and that genetic modifiers and other familial factors may influence risk specifically for either breast or ovarian cancer.