Zhao Jianwei, Liu Lin, Zhang Anqing, Chen Qin, Fang Wenxiang, Zeng Lizhi, Lu Jiachun
The Institute for Chemical Carcinogenesis, the State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong 510182, China; ; Baiyun Women and Children Hospital, Guangzhou, Guangdong 510400, China;
J Biomed Res. 2013 May;27(3):193-201. doi: 10.7555/JBR.27.20130013. Epub 2013 Apr 15.
Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the recognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME1 (i.e.,Ile350Thr: rs12450550T > C and Glu69Asp: rs3760413T > G) and breast cancer risk. We found that compared to the common Ile/Ile genotype, the Thr variant genotypes (Thr/Ile + Thr/Thr) conferred a 1.47-fold increased risk of breast cancer (OR=1.47, 95% CI=1.13-1.92). The variant Ile350Thr was also associated with early onset of breast cancer (r = -0.116, P = 0.002). The mean age of onset was 44.4 years for Thr/Thr genotype carriers and 46.5 years for Thr/Ile genotype carriers, which was significantly lower than that (49.4 years) for Ile/Ile genotype carriers (P = 0.006). Moreover, no significant association was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.
必需减数分裂内切核酸酶1同源物1（EME1）是一种关键的DNA修复蛋白，参与DNA双链断裂的识别和修复。EME1基因缺陷可导致自发的基因组不稳定，从而促进肿瘤发生。我们假设EME1的外显子变异赋予乳腺癌遗传易感性。在一项对748例乳腺癌患者和778例正常对照的病例对照研究中，我们分析了EME1的两个外显子变异（即Ile350Thr：rs12450550T>C和Glu69Asp：rs3760413T>G）与乳腺癌风险之间的关联。我们发现，与常见的Ile/Ile基因型相比，Thr变异基因型（Thr/Ile + Thr/Thr）使患乳腺癌的风险增加了1.47倍（OR = 1.47，95% CI = 1.13 - 1.92）。变异Ile350Thr也与乳腺癌的早发有关（r = -0.116，P = 0.002）。Thr/Thr基因型携带者的平均发病年龄为44.4岁，Thr/Ile基因型携带者为46.5岁，显著低于Ile/Ile基因型携带者的发病年龄（49.4岁）（P = 0.006）。此外，未观察到Glu69Asp变异与乳腺癌风险之间存在显著关联。我们的研究结果表明，EME1变异Ile350Thr会增加患乳腺癌的风险并导致早发。
