Terry Fox Cancer Research Lab, China Medical University Hospital, Taichung, Taiwan, R.O.C.
BMC Cancer. 2011 May 17;11:174. doi: 10.1186/1471-2407-11-174.
The DNA repair gene Ku70, an important member of non-homologous end-joining repair system, is thought to play an important role in the repairing of DNA double strand breaks. It is known that defects in double strand break repair capacity can lead to irreversible genomic instability. However, the polymorphic variants of Ku70, have never been reported about their association with gastric cancer susceptibility.
In this hospital-based case-control study, the associations of Ku70 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms with gastric cancer risk in a Taiwanese population were investigated. In total, 136 patients with gastric cancer and 560 age- and gender-matched healthy controls recruited from the China Medical Hospital in Taiwan were genotyped.
As for Ku70 promoter T-991C, the ORs after adjusted by age and gender of the people carrying TC and CC genotypes were 2.41 (95% CI = 1.53-3.88) and 3.21 (95% CI = 0.96-9.41) respectively, compared to those carrying TT wild-type genotype. The P for trend was significant (P < 0.0001). In the dominant model (TC plus CC versus TT), the association between Ku70 promoter T-991C polymorphism and the risk for gastric cancer was also significant (adjusted OR = 2.48, 95% CI = 1.74-3.92). When stratified by age and gender, the association was restricted to those at the age of 55 or elder of age (TC vs TT: adjusted OR = 2.52, 95% CI = 1.37-4.68, P = 0.0139) and male (TC vs TT: adjusted OR = 2.58, 95% CI = 1.33-4.47, P = 0.0085). As for the other three polymorphisms, there was no difference between both groups in the distributions of their genotype frequencies.
In conclusion, the Ku70 promoter T-991C (rs5751129), but not the Ku70 promoter C-57G (rs2267437), promoter A-31G (rs132770) or intron 3 (rs132774), is associated with gastric cancer susceptibility. This polymorphism may be a novel useful marker for gastric carcinogenesis.
Ku70 是非同源末端连接修复系统的重要成员之一，被认为在修复 DNA 双链断裂方面发挥着重要作用。已知双链断裂修复能力的缺陷会导致不可逆转的基因组不稳定。然而，Ku70 的多态性变体与胃癌易感性之间的关联从未被报道过。
本研究采用基于医院的病例对照研究，在台湾中国医药大学附属医院共招募了 136 名胃癌患者和 560 名年龄和性别匹配的健康对照者，以探讨 Ku70 启动子 T-991C(rs5751129)、启动子 G-57C(rs2267437)、启动子 A-31G(rs132770)和内含子 3(rs132774)多态性与胃癌风险的相关性。
对于 Ku70 启动子 T-991C，携带 TC 和 CC 基因型的人群在调整年龄和性别后，其 OR 值分别为 2.41(95%CI=1.53-3.88)和 3.21(95%CI=0.96-9.41)，与携带 TT 野生型基因型的人群相比。趋势检验的 P 值<0.0001。在显性模型(TC 加 CC 与 TT)中，Ku70 启动子 T-991C 多态性与胃癌风险之间的关联也具有统计学意义(调整后的 OR=2.48，95%CI=1.74-3.92)。按年龄和性别分层后，这种关联仅限于年龄在 55 岁或 55 岁以上的人群(TC 与 TT：调整后的 OR=2.52，95%CI=1.37-4.68，P=0.0139)和男性(TC 与 TT：调整后的 OR=2.58，95%CI=1.33-4.47，P=0.0085)。对于其他三个多态性，两组之间基因型频率的分布没有差异。
总之，Ku70 启动子 T-991C(rs5751129)，而不是 Ku70 启动子 C-57G(rs2267437)、启动子 A-31G(rs132770)或内含子 3(rs132774)，与胃癌易感性相关。这种多态性可能是胃癌发生的一个新的有用的标志物。
