Tryggvadottir Laufey, Olafsdottir Elinborg J, Gudlaugsdottir Sigfridur, Thorlacius Steinunn, Jonasson Jon G, Tulinius Hrafn, Eyfjord Jorunn E
Icelandic Cancer Registry, Reykjavík, Iceland.
Breast Cancer Res. 2003;5(5):R121-8. doi: 10.1186/bcr619. Epub 2003 Jun 24.
Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear.
In a case-control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis.
An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years.
The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.
BRCA基因的种系突变会显著增加患乳腺癌的风险。在一般人群中，乳腺癌风险受初潮年龄、首次生育年龄、生育次数和母乳喂养时长的影响。对于突变携带者而言是否如此尚不清楚。
在一项病例对照研究中，该研究嵌套于冰岛癌症检测诊所的一项基于人群的队列研究中，定义了两组病例，根据出生年份、诊断年龄以及提供生殖因素信息时的年龄进行匹配：100名冰岛始祖BRCA2突变999del5的携带者，以及361名BRCA2阴性病例。诊断时的平均年龄为48岁。在一组匹配的未受影响的对照中有1000名女性。采用条件逻辑回归进行分析。
生育次数增加与BRCA2阴性病例患乳腺癌风险降低相关，但与BRCA2阳性病例无关。仅在突变携带者中观察到风险与母乳喂养时长之间存在负相关。这些关联无统计学意义，但这两个变量的效应根据突变状态有显著差异（分别与生育次数和母乳喂养时长的交互作用的P值为0.007和0.045）。当将分析限制在40岁以上诊断的女性时，这种情况依然存在。
对于有害BRCA2突变的携带者和非携带者而言，乳腺癌与怀孕次数以及乳腺癌与母乳喂养时长之间的关联并不相同。结合其他流行病学和实验室研究来看，这可能表明BRCA2基因的产物具有与乳腺上皮组织分化相关的功能。
