Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes:: a familial study
Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes:: a familial study
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DOI：
10.1016/s0140-6736(05)67627-1
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发表时间：
2005-10-01
期刊：
影响因子：
168.9
通讯作者：
Peto, J
中科院分区：
文献类型：
--
作者：
Johnson, N;Fletcher, O;Peto, J
背景：等位基因CHEK2*1100delC会使未经选择的女性患乳腺癌的风险增加一倍，但对有乳腺癌家族史的女性，特别是双侧乳腺癌，可能会带来更大的风险。我们的目的是测量双侧乳腺癌患者亲属患乳腺癌的风险。方法通过英国癌症登记系统对469例双侧乳腺癌患者进行CHEK2*1100delC基因分型。在携带者和非携带者的一级亲属中计算乳腺癌、前列腺癌和所有其他癌症的标准化发病率(SIRS)和累积风险。发现CHEK2野生型患者的亲属患女性乳腺癌的人群风险是女性乳腺癌的三倍(145例：SIR 3.48(95%可信区间2.96-4.09)，是前列腺癌风险的两倍(34例：SIR 2.41，1.67-3.36)，以及大量男性乳腺癌的人群风险(5例：SIR 15.06，4.92-35.36)。CHEK2*1100delC携带者的亲属患乳腺癌(8例：SIR 12.11，5.23-23.88)和前列腺癌(2例：SIR 9.87，1.20-35.67)的风险显著增加。在有双侧疾病家族史的女性中，CHEK2*1100delC具有高的终生风险，可能对预测性测试有用。双侧乳腺癌病例及其家族可能为识别额外的低外显性乳腺癌基因提供有效的基础。
Background The allele CHEK2*1100delC doubles the risk of breast cancer in unselected women, but could confer a greater risk in women with a family history of the disease, particularly of bilateral breast cancer. Our aim was to measure the risk of breast cancer in relatives of women with bilateral breast cancer who were carriers of this allele.Methods A population-based series of 469 bilateral breast cancer cases ascertained through English cancer registries were genotyped for CHEK2*1100delC. Standardised incidence ratios (SIRs) and cumulative risks were calculated for breast cancer, prostate cancer, and all other cancers in the first-degree relatives of carriers and non-carriers.Findings The relatives of bilateral cases who were wild-type for CHEK2 had three times the population risk of female breast cancer (145 cases: SIR 3.48 (95% CI 2.96-4.09), twice the risk of prostate cancer (34 cases: SIR 2.41, 1.67-3.36) and a large excess of male breast cancer (five cases: SIR 15.06, 4.92-35.36). Relatives of those who were carriers of CHEK2*1100delC had a substantially higher risk of breast cancer (eight cases: SIR 12.11, 5.23-23.88) and possibly prostate cancer (two cases: SIR 9.87, 1.20-35.67).Interpretation These data suggest a multiplicative interaction between CHEK2*1100delC and other unknown susceptibility genes. in women with a family history of bilateral disease, CHEK2*1100delC confers a high lifetime risk and might be useful for predictive testing. Bilateral breast cancer cases and their families are likely to provide an efficient basis for identification of additional low-penetrance breast-cancer genes.