Chuang Chin-Liang, Wang Chung-Hsing, Hsu Chang-Hsien, Hsiao Chieh-Lun, Chen Guan-Liang, Yen Shiou-Ting, Li Hsin-Ting, Chang Wen-Shin, Tsai Chia-Wen, Wang Shou-Cheng, Bau DA-Tian
Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2017 May;37(5):2417-2423. doi: 10.21873/anticanres.11581.
BACKGROUND/AIM: Nijmegen breakage syndrome 1 (NBS1) is a component of MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and maintenance of chromosomal integrity. Failure in DNA damage response affects the level of cell survival, increases the frequency of gene mutation or chromosomal instability and other cellular phenotypic abnormalities, which are the important mechanisms of carcinogenesis. However, the contribution of variant NBS1 genotypes to lung cancer is not known. The current study aimed to evaluate the contribution of the common variant NBS1 Glu185Gln (rs1805794, E185Q) genotypes to the risk of lung cancer.
The contributions of the NBS1 Glu185Gln genotypes to lung cancer risk were investigated among 358 patients with lung cancer and 716 age- and gender-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
GG, CG and CC NBS1 Glu185Gln genotype percentages were 45.2%, 43.9% and 10.9% in the patient group and 46.1%, 45.1% and 8.8% in the non-cancer control group, respectively (p for trend=0.5423). Analysis of allelic frequency distributions showed that the C allele of NBS1 Glu185Gln did not increase lung cancer susceptibility (p=0.4916). Interestingly, the CC genotypes at NBS1 Glu185Gln enhanced the risk of lung cancer among the males adjusted odds ratio (aOR)=1.85, 95% confidence interval (CI)=1.12-2.83 and among the smokers (aOR=1.76, 95% CI=1.09-2.64) but not among the females and non-smokers.
The CC genotype of NBS1 Glu185Gln may increase lung cancer risk only for males and smokers and may serve as a practical marker for early detective and predictive purposes of lung cancer.
背景/目的：尼美根断裂综合征1（NBS1）是MRE11/RAD50/NBS1复合物（MRN）的一个组成部分，在细胞对DNA损伤的反应及维持染色体完整性方面发挥关键作用。DNA损伤反应失败会影响细胞存活水平，增加基因突变频率或染色体不稳定性以及其他细胞表型异常，这些都是致癌的重要机制。然而，NBS1基因变异型对肺癌的影响尚不清楚。本研究旨在评估常见变异型NBS1 Glu185Gln（rs1805794，E185Q）基因型对肺癌风险的影响。
通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，在358例肺癌患者和716例年龄及性别匹配的健康对照者中，研究NBS1 Glu185Gln基因型对肺癌风险的影响。
患者组中NBS1 Glu185Gln的GG、CG和CC基因型百分比分别为45.2%、43.9%和10.9%，非癌症对照组分别为46.1%、45.1%和8.8%（趋势p值 = 0.5423）。等位基因频率分布分析显示，NBS1 Glu185Gln的C等位基因不会增加肺癌易感性（p = 0.4916）。有趣的是，NBS1 Glu185Gln的CC基因型在男性（调整优势比[aOR]=1.85，95%置信区间[CI]=1.12 - 2.83）和吸烟者（aOR = 1.76，95% CI = 1.09 - 2.64）中增加了肺癌风险，但在女性和非吸烟者中未增加。
NBS1 Glu185Gln的CC基因型可能仅增加男性和吸烟者的肺癌风险，可作为肺癌早期检测和预测的实用标志物。
