位于染色体上的BRCA1或BRCA2基因
《临床肿瘤学杂志》10月31日在线发表的一项纳入3,047名受试者的以人群为基础的研究显示，如果一名女性不像其亲人那样携带BRCA1或BRCA2突变，则其罹患乳腺癌的风险并不高于常人。
部分近期研究提示，家族特异性突变的非携带者发生乳腺癌的风险可能比一般人群增加2~5倍，虽然低于携带者(风险增加5~20倍)，但仍值得加强乳腺癌筛查。而其他研究并未发现非携带者的风险增加。
为了澄清这一问题，美国斯坦福大学的Allison W. Kurian博士及其同事利用美国、澳大利亚和加拿大的人群癌症注册数据，评估了乳腺癌风险。研究者确定了3,047个有1名女性成员在相对年轻时即发生乳腺癌的家族，这些患者及其女性一级亲属均接受了BRCA1和BRCA2突变基因筛查。
结果显示，3个国家的女性中的突变流行情况、乳腺癌和卵巢癌发病率及发病年龄均相似。共有160个家族存在BRCA1突变，132个家族存在BRCA2突变(J. Clin. Oncol. 2011 Oct. 31 [doi:10.1200.JCO.2010.34.4440])。与无BRCA1或BRCA2突变的家族中的女性相比，家族特异性突变的非携带者发生乳腺癌的风险并不显著增高，相对风险为0.39。
Kurian博士等人总结认为，上述结果表明，目前临床上将未遗传家族特异性BRCA而且没有其他强危险因素的女性视为一般人群进行乳腺癌筛查策略的做法是正确的。既往报告非携带者风险增加的研究可能高估了风险，因为这些研究纳入的受试者来自一般人群而非来自有乳腺癌患者的家族，而后一组受试者更常接受筛查，从而比一般人群更可能被诊断为乳腺癌。
本项研究获得了美国国立癌症研究所、美国国立卫生研究院、加拿大安大略癌症治疗、美国加州癌症预防研究所和澳大利亚墨尔本大学的支持。无相关利益冲突披露。
纪念Sloan-Kettering 癌症中心和Weill Cornell医学院的Mark Robson博士在随刊述评中指出，Kurian博士等人的研究结果与既往前瞻性队列研究的结果一致(J. Clin. Oncol. 2011 Oct. 31 [doi:10.1200/JCO.2011.37.6483])。但与既往研究一样，本项研究也不能完全排除家族特异性BRCA突变的非携带者的乳腺癌风险仍略高于一般人群的可能性。（生物探索）
相关英文论文摘要：
Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry
Purpose Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs).
Patients and Methods Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors.
Results We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases.
Conclusion These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.
