The involvement of Kras gene 3′-UTR polymorphisms in risk of cancer and influence on patient response to anti-EGFR therapy in metastatic colorectal cancer: a meta-analysis

BACKGROUND: 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. METHODS: 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: 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. CONCLUSION: 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.