中文摘要：

目的研究上海地区非BRCA1／2基因突变的遗传倾向乳腺癌中CHEK2基因c．1100delC突变的携带情况及可能的作用。方法研究对象来自114例遗传倾向性乳腺癌，包括家族性乳腺癌76例，其中8例发病年龄低于40岁；38例单纯早发性乳腺癌（发病年龄〈40岁）。对照组为121名无乳腺癌的健康女性，静脉血中提取基因组DNA，对CHEK2基因的第10～14外显子进行长片段PCR扩增，PCR产物再进行含突变的第10外显子的扩增。突变分析全部由DNA直接测序进行鉴定。结果研究人群和对照人群中都没有发现c．1100delC的突变；在3例（3／114，2．6％）家族性乳腺癌中发现邻近c．1100delC的新的错义突变位点1111C〉T（p-His371 Tyr），对照组中则无此突变发现。结论CHEK2基因c．1100delC突变可能是中国人群罕见的突变位点，在中国人乳腺癌遗传易感性中的作用非常有限；1111C〉T可能与中国上海地区遗传倾向乳腺癌低度外显的易感性有关，需要进行进一步研究确认。

英文摘要：

Objective To investigate the prevalence of CHEK2 c. 1100delC mutation among non- BRCA1/BR- CA2 familial/early-onset breast cancer patients in Shanghai. Methods One hundred and fourteen non-BRCA1/BRCA2 hereditary breast cancer patients were analyzed, among whom 76 cases had at least one first-degree relative affected with breast cancer and 38 eases were diagnosed as breast cancer below the age of 40 years without family history. The mutation genotyping of CHEK2 c. 1100delC were carried out through long-range PCR amplifying of exons 10-14, and followed by amplification of exon 10 and then DNA direct sequencing. Results No e. 1100delC frame-shift mutation was identified in our studied population. One novel missense mutation 1111C 〉 T （p. His371Tyr）, located in kinase catalytic domain, was found in 3 familial breast cancer cases but no one in control group. Conclusion CHEK2 c. 1100delC is rare variant for Chinese population and may not contribute to predisposition for hereditary breast cancer in Shanghai. Novel variant - 1111C 〉 T could be in association with genetic susceptibility to breast cancer. A further study is needed to confirm the results.