Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO)
Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO)
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DOI：
10.1007/s10549-011-1655-3
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发表时间：
2011-12-01
影响因子：
3.8
通讯作者：
Andrieu, Nadine
中科院分区：
文献类型：
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作者：
Lecarpentier, Julie;Nogues, Catherine;Andrieu, Nadine
BRCA1/2 的种系突变会带来患乳腺癌 (BC) 的高风险，但这种风险的程度因各种因素而异。尽管存在争议，但有数据支持等位基因风险异质性的假设。我们根据法国研究 GEEPSO 中记录的突变位置评估了 BC 风险的变化。由于本研究中的女性是从高风险家庭中选择的，因此通过使用加权 Cox 回归模型消除了对受影响女性的过度采样。如果女性患有任何癌症，则在诊断日期进行审查；如果未受影响，则在访谈日期进行审查。总共选择了 990 名女性进行分析：379 名被归类为受影响，611 名被归类为未受影响。对于 BRCA1，有一些证据表明中部区域的 BC 风险较低（密码子 374-1161）（HR = 0.59，P = 0.04）。对于 BRCA2，有强有力的证据表明某个区域的风险较低（密码子 957-1827）（HR = 0.35，P = 0.005），而一个区域的风险较高（密码子 2546-2968）（HR = 3.56，P = 0.01）。此外，我们发现胸部 X 光辐射暴露与 BC 风险之间存在重要关联（HR = 4.29，P < 10(-3)），吸烟超过 21 包年与 BC 风险之间存在正相关（HR = 2.09，P = 0.04）。根据 BRCA1 和 BRCA2 突变的位置，未发现与胸部 X 光照射、吸烟和饮酒相关的 BC 风险存在显着差异。我们的研究结果与 BRCA1/2 中心区域的 BC 风险较低的结果一致。描述了 BRCA2 中的一个新的高风险区域。考虑到环境和生活方式的改变，突变的位置可能在 BRCA 突变携带者的临床管理中很重要。
Germline mutations in BRCA1/2 confer a high risk of breast cancer (BC), but the magnitude of this risk varies according to various factors. Although controversial, there are data to support the hypothesis of allelic-risk heterogeneity. We assessed variation in BC risk according to the location of mutations recorded in the French study GENEPSO. Since the women in this study were selected from high-risk families, oversampling of affected women was eliminated by using a weighted Cox-regression model. Women were censored at the date of diagnosis when affected by any cancer, or the date of interview when unaffected. A total of 990 women were selected for the analysis: 379 were classified as affected, 611 as unaffected. For BRCA1, there was some evidence of a central region where the risk of BC is lower (codons 374-1161) (HR = 0.59, P = 0.04). For BRCA2, there was a strong evidence for a region at decreased risk (codons 957-1827) (HR = 0.35, P = 0.005) and for one at increased risk (codons 2546-2968) (HR = 3.56, P = 0.01). Moreover, we found an important association between radiation exposure from chest X-rays and BC risk (HR = 4.29, P < 10(-3)) and a positive association between smoking more than 21 pack-years and BC risk (HR = 2.09, P = 0.04). No significant variation in BC risk associated with chest X-ray exposure, smoking, and alcohol consumption was found according to the location of the mutation in BRCA1 and BRCA2. Our findings are consistent with those suggesting that the risk of BC is lower in the central regions of BRCA1/2. A new high-risk region in BRCA2 is described. Taking into account environmental and lifestyle modifiers, the location of mutations might be important in the clinical management of BRCA mutation carriers.