Medical College, Southeast University, Nanjing, Jiangsu, People's Republic of China ; Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Onco Targets Ther. 2014 Aug 25;7:1487-96. doi: 10.2147/OTT.S65496. eCollection 2014.
Genetic variation of the Kras oncogene is a candidate factor for increasing susceptibility to carcinoma and modulating response of metastatic colorectal cancer (mCRC) patients treated with anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR). However, results from an increasing number of studies concerning the association of Kras gene rs712 and rs61764370 polymorphisms with risk of cancer and treatment of mCRC using anti-EGFR remain equivocal.
Risk associations were evaluated in 1,661 cases and 2,139 controls from six studies concerning rs712 and 14,796 cases and 14,985 controls from 29 studies concerning rs61764370. Response association was also examined in a subset of four studies pertaining to rs61764370 and anti-EGFR treatment in mCRC.
Results of a meta-analysis showed that allele T (P-value of heterogeneity test [P H] =0.08, odds ratio [OR] =1.33, 95% confidence interval [CI]: 1.08-1.64) and genotype GT/TT (P H=0.14, OR =1.30, 95% CI: 1.10-1.55) in rs712 were strongly associated with cancer in Chinese subjects. No evidence of association was observed between rs712 and risk of cancer in the overall population or between rs61764370 and ovarian, breast, colorectal, or non-small-cell lung cancer risk in the Caucasian population. No significant association was found between rs61764370 and patient response to anti-EGFR therapy in mCRC.
The findings not only provide further evidence that allele T of rs712 increases genetic predisposition to cancer in Chinese population, but also no significant association between rs61764370 and cancer risk in Caucasian population, and suggest that genotype GT/TT of rs61764370 may not be a biomarker for predicting clinical outcome of anti-EGFR therapy in mCRC.
Kras 癌基因的遗传变异是增加患癌风险和调节转移性结直肠癌（mCRC）患者对抗表皮生长因子受体单克隆抗体（anti-EGFR）治疗反应的候选因素。然而，越来越多的研究结果表明，Kras 基因 rs712 和 rs61764370 多态性与癌症风险和 mCRC 患者使用抗 EGFR 治疗的相关性仍存在争议。
在 6 项研究中，对 1661 例病例和 2139 例对照(rs712)和 29 项研究中，对 14796 例病例和 14985 例对照(rs61764370)进行风险关联评估。还对四项研究中的一个亚组(rs61764370)和 mCRC 中抗 EGFR 治疗的反应相关性进行了检查。
荟萃分析结果表明，在中国人群中，等位基因 T（异质性检验 P 值[P H] =0.08，比值比[OR] =1.33，95%置信区间[CI]：1.08-1.64）和基因型 GT/TT（P H=0.14，OR =1.30，95% CI：1.10-1.55）与癌症密切相关。在总体人群中，未观察到 rs712 与癌症风险之间存在关联，在白种人群中，也未观察到 rs61764370 与卵巢癌、乳腺癌、结直肠癌或非小细胞肺癌风险之间存在关联。在 mCRC 患者中，未发现 rs61764370 与抗 EGFR 治疗的反应之间存在显著关联。
这些发现不仅进一步证明了 rs712 的等位基因 T 增加了中国人群患癌症的遗传易感性，而且还表明 rs61764370 与白种人群的癌症风险之间没有显著关联，并且提示 rs61764370 的 GT/TT 基因型可能不是预测 mCRC 中抗 EGFR 治疗临床效果的生物标志物。
