Goldgar D E, Fields P, Lewis C M, Tran T D, Cannon-Albright L A, Ward J H, Swensen J, Skolnick M H
Department of Medical Informatics, University of Utah, Salt Lake City.
J Natl Cancer Inst. 1994 Feb 2;86(3):200-9. doi: 10.1093/jnci/86.3.200.
Mutation of a specific, but as yet unidentified, gene BRCA1 on chromosome 17q results in increased susceptibility to breast and ovarian cancer. It is important to know the effects of this gene in terms of the age-specific risks of these cancers and the potential interaction of this gene with other known risk factors.
We performed detailed studies on a large multigenerational family, in which there is known 17q-linked breast and ovarian cancer, in order to characterize the effects of the BRCA1 mutation on development of breast and ovarian cancer.
Data from the Utah Population Database were used to identify a family (identified as K2082) with a cluster of premenopausal breast cancer and ovarian cancer at any age. Blood samples from 195 members of the family were obtained and these individuals were genotyped for a series of four chromosome 17q polymorphic markers. Information on reproductive history, cancer incidence and treatment, and lifestyle factors was collected on 72 women in the family by questionnaire or through contact with living relatives.
Odds in favor of linkage of breast and ovarian cancer in this family to the BRCA1 region of chromosome 17q are greater than 10(8) to 1. The estimated risks for breast or ovarian cancer because of the BRCA1 mutation in this family are 40% by age 50 years and 90% by age 70. No differences between affected and unaffected older BRCA1 gene carriers were observed for a number of known epidemiologic risk factors for these cancers. The gender of the parent from whom the mutant BRCA1 allele was inherited was significantly associated with phenotypic expression (P = .04). A recombinant which places BRCA1 distal to the marker Mfd191 was observed.
Women with the BRCA1 mutation are at increased risk of developing breast and ovarian cancer. In our study population, the mutation appears to confer a lower risk of cancer at younger ages than found in previous studies. Continued interaction with family K2082 will be useful in longitudinal follow-up studies and in studies of the psychosocial implications of providing DNA diagnosis of BRCA1.
位于17号染色体q臂上的一个特定但尚未明确的基因BRCA1发生突变会导致患乳腺癌和卵巢癌的易感性增加。了解该基因在这些癌症的年龄特异性风险方面的影响以及该基因与其他已知风险因素的潜在相互作用非常重要。
我们对一个大型多代家族进行了详细研究，该家族中已知存在与17号染色体q臂相关的乳腺癌和卵巢癌，以确定BRCA1突变对乳腺癌和卵巢癌发生发展的影响。
利用犹他州人口数据库的数据识别出一个家族（编号为K2082），该家族存在绝经前乳腺癌和任何年龄段的卵巢癌聚集现象。采集了该家族195名成员的血样，并对这些个体进行了一系列四个17号染色体q臂多态性标记的基因分型。通过问卷调查或与在世亲属联系，收集了该家族72名女性的生殖史、癌症发病率和治疗情况以及生活方式因素等信息。
该家族中乳腺癌和卵巢癌与17号染色体q臂上BRCA1区域连锁的优势比大于10的8次方比1。由于该家族中BRCA1突变，估计到50岁时患乳腺癌或卵巢癌的风险为40%，到70岁时为90%。对于这些癌症的一些已知流行病学风险因素，未观察到受影响和未受影响的老年BRCA1基因携带者之间存在差异。继承突变BRCA1等位基因的亲本性别与表型表达显著相关（P = 0.04）。观察到一个重组体，其将BRCA1定位在标记Mfd191的远端。
携带BRCA1突变的女性患乳腺癌和卵巢癌的风险增加。在我们的研究人群中，该突变在年轻时似乎比先前研究中发现的患癌风险更低。与K2082家族继续合作，将有助于进行纵向随访研究以及研究提供BRCA1基因诊断的心理社会影响。
