Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer
Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer
复制标题
DOI：
10.1158/0008-5472.can-07-1501
复制
发表时间：
2007-10-01
期刊：
影响因子：
11.2
通讯作者：
Auerbach, Arleen D.
中科院分区：
文献类型：
--
作者：
Berwick, Marianne;Satagopan, Jaya M.;Auerbach, Arleen D.
Fanconi贫血(FA)是一种罕见的常染色体隐性遗传病，其特征是在被诊断为该综合征的人中患癌症的风险大大增加。关于FA杂合子是否会增加癌症风险的问题，对那些有可能成为携带者的人来说是非常重要的。为了解决这个问题，我们组成了一个祖父母队列，这些祖父母是通过国际范科尼贫血登记处确定的先证者。我们获得了知情同意，一份简短的问卷，以及血液或口腔拭子DNA。在先证者确诊并完成互补研究或DNA测序后，对可能的携带者和非携带者进行突变分析。使用监测、流行病学和最终结果登记处和康涅狄格州癌症登记处计算标准化发病率比(SIR)，以将祖父母和其他亲属的观察癌症发病率与预期癌症发病率进行比较。在944名参与研究的受试者(784名祖父母和160名其他亲属)中，没有迹象表明总体癌症发病率会增加。另一方面，在携带者祖母中观察到的乳腺癌发病率明显高于预期[SIR，1.7；95%可信区间(95%CI)，1.1-2.7]。在祖母中，那些携带FANCC突变的人被发现是风险最高的(SIR，2.4；95%CI，1.1-5.2)。总体而言，在这项针对Fanconi亲属的研究中，FA杂合子患癌症的风险没有增加，尽管有一些证据表明FANCC突变可能是乳腺癌的易感等位基因。
Fanconi anemia (FA) is a rare autosomal recessive disease characterized by a greatly increased risk of cancer among those diagnosed with the syndrome. The question as to whether FA heterozygotes are at increased risk for cancer is of great importance to those at risk for being a carrier. To address this question, we formed a cohort of grandparents of probands identified through the International Fanconi Anemia Registry. We obtained informed consent, a short questionnaire, and either blood or buccal swab DNA. After diagnosis of the proband was confirmed and complementation studies or DNA sequencing on the proband were completed, mutation analyses of the putative carriers and noncarriers was carried out. Standardized incidence ratios (SIR) were calculated to compare the observed cancer incidence of the grandparents and other relatives with the expected rates of cancer, using the Surveillance, Epidemiology, and End Results registries and the Connecticut Cancer registry. In the 944 study subjects who participated (784 grandparents and 160 other relatives), there was no suggestion of an increase in overall cancer incidence. On the other hand, a significantly higher rate of breast cancer than expected was observed among carrier grandmothers [SIR, 1.7; 95% confidence interval (95% CI), 1.1-2.7]. Among the grandmothers, those who were carriers of FANCC mutations were found to be at highest risk (SIR, 2.4; 95% Cl, 1.1-5.2). Overall, there was no increased risk for cancer among FA heterozygotes in this study of Fanconi relatives, although there is some evidence that FANCC mutations are possibly breast cancer susceptibility alleles.