Genetic Variants in the Wingless Antagonist Genes (, , and ) Predict the Overall Survival and Prognosis of North Indian Lung Cancer Patients Treated with Platinum-Based Doublet Chemotherapy.

To investigate the prognostic implication of genetic variants within the wingless (Wnt) antagonist genes (, , and ) in North Indian lung cancer patients. A total of 212 subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique for 18 polymorphic sites in , , , , , and . Overall survival (OS) was estimated using the Kaplan-Meier survival analysis, and adjusted hazard ratio (HR) was obtained using the Cox regression method. It was observed that the unfavorable genotypes of the three variants collectively (rs447372, rs419558, and rs17037102) exhibited a highly decreased rate of death (adjusted HR = 0.37,  = 0.03). Adenocarcinoma (ADCC) patients carrying the heterozygous (CT) genotype for rs2073664 showed a better OS compared with wild genotype (log rank  = 0.01). The two exonic variants ( and ) of gene showed contrasting results, where the ADCC subjects having TT genotype for showed a better prognosis (adjusted HR = 0.48,  = 0.003) and those with TT genotype for showed a poor prognosis in small-cell lung carcinoma patients (adjusted HR = 2.33,  = 0.02). The intronic variant on the other hand indicated a highly increased death risk in ADCC patients with GG genotype. Survival tree analysis depicted DKK4 rs2073664 as the major contributor in predicting the survival of the lung cancer patients. Node 3 exhibited the lowest death rate (HR = 0.04,  = 0.008) and better median survival time (9 months vs. 3 months) when compared with reference node. A cumulative effect of three variants of gene along with rs2073664 can jointly predict the survival as shown by tree analysis.