Chen P L, Sellers T A, Rich S S, Potter J D, Folsom A R
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454, USA.
Genet Epidemiol. 1995;12(4):401-15. doi: 10.1002/gepi.1370120408.
Inheritance of a major susceptibility gene for breast cancer has been primarily investigated in families with early-onset disease. However, familial clustering of late-onset breast cancer is well documented, and genetic factors may also be relevant. In the Iowa Women's Health Study, we evaluated evidence for a major gene after allowing for measured environmental risk factors. Two hundred sixty-five incident breast cancer probands were identified from a prospective cohort study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree development form was mailed to the probands to ascertain all first-degree female relatives. A questionnaire and body measurement protocol were mailed to identified living relatives or surrogates. Segregation analyses were conducted on a total of 1,145 women in 251 families using regressive models as implemented in S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier-age-at-onset provided the best fit to the data. Incorporation of measured environmental risk factors as covariates yielded no significant improvements in the likelihoods. Approximately 50% of this population could be expected to carry a late-onset breast cancer susceptibility gene, and 23% of the population is susceptible because of the environment in which they live. Homozygous gene carriers are predicted to have a mean age-at-onset of 48 years, over 20 years earlier than heterozygotes; few cases would be expected among non-gene carriers. In conclusion, the transmission pattern of late-onset breast cancer may be determined by a common susceptibility gene.
乳腺癌主要易感性基因的遗传情况主要是在早发性疾病家族中进行研究的。然而，晚发性乳腺癌的家族聚集现象有充分记录，遗传因素可能也与之相关。在爱荷华州女性健康研究中，我们在考虑了已测量的环境风险因素后，评估了主要基因的证据。从1986年基线时年龄在55至69岁的41837名女性的前瞻性队列研究中确定了265名乳腺癌先证者。向先证者邮寄了一份家系发展表格，以确定所有一级女性亲属。向已确定的在世亲属或代理人邮寄了一份问卷和身体测量方案。使用S.A.G.E.中实施的回归模型，对251个家庭中的1145名女性进行了分离分析。一个导致发病年龄提前的等位基因的孟德尔共显性遗传最符合数据。将已测量的环境风险因素作为协变量纳入并没有显著提高似然性。预计该人群中约50%携带晚发性乳腺癌易感性基因，23%的人群因生活环境而易感。预计纯合基因携带者的平均发病年龄为48岁，比杂合子早20多年；预计非基因携带者中很少有病例。总之，晚发性乳腺癌的遗传模式可能由一个常见的易感性基因决定。
