Breast cancer risk in ashkenazi BRCA1/2 mutation carriers: Effects of reproductive history
Breast cancer risk in ashkenazi BRCA1/2 mutation carriers: Effects of reproductive history
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DOI：
10.1097/00001648-200205000-00004
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发表时间：
2002-05-01
期刊：
影响因子：
5.4
通讯作者：
Struewing, JP
中科院分区：
文献类型：
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作者：
Hartge, P;Chatterjee, N;Struewing, JP
背景初次生育年龄越小，产次越多，患乳腺癌的风险通常越低，但这种风险降低是否适用于BRCA 1或BRCA 2基因突变的女性尚不清楚。在1996年进行的一项以华盛顿社区为基础的研究中，我们对5318名德系犹太人进行了三种BRCA 1/2创始人突变的检测，并确定了120名突变携带者。应用扩展的“亲属队列”分析，我们比较了生育对携带者和非携带者乳腺癌风险的影响。我们还对288名被诊断为乳腺癌的参与者进行了病例分析。在非携带者中，首次生育年龄每增加5岁，乳腺癌的估计相对危险度（RR）增加5%（RR = 1.05; 95%置信区间[CI] = 0.97-1.15）。相比之下，突变携带者的估计风险随着年龄每增加5岁而下降（RR = 0.65; 95%CI = 0.37 -1.16）。在288名乳腺癌幸存者中，携带者与非携带者的比较也显示，在BRCA 1或BRCA 2突变的情况下，早产没有保护作用。目前尚不清楚公认的乳腺癌风险因素是否以同样的方式在携带BRCA 1或BRCA 2基因突变的女性中发挥作用。
Background. Younger age at first birth and greater parity generally reduce the risk of developing breast cancer, but whether this reduced risk holds in women with a mutation in the BRCA1 or BRCA2 gene is unknown.Methods. In a Washington DC community-based study conducted in 1996, we tested 5318 Ashkenazi Jews for three BRCA1/2 founder mutations and identified 120 mutation carriers. Applying an extension of the "kin-cohort" analysis, we compared the effects of reproduction on breast cancer risk in carriers and noncarriers. We also used a case-case analysis among 288 participants who had been diagnosed with breast cancer.Results. In noncarriers, the estimated relative risk (RR) of breast cancer rose 5% with each 5-year increment in age at first birth (RR = 1.05; 95% confidence interval [CI] = 0.97-1.15). By contrast, the estimated risk in mutation carriers fell with each 5-year increment in age (RR = 0.65; 95% Cl = 0,37-1.16). Among the 288 participants who were breast cancer survivors themselves, the comparison of carriers with noncarriers also showed no protection associated with early birth in the presence of a mutation in BRCA1 or BRCA2.Conclusions. It is not yet clear whether the recognized breast cancer risk factors operate in the same way in women who carry a mutation in the BRCA1 or BRCA2 genes.