A specific diplotype defined by PPP1R13L rs1970764, CD3AP rs967591 and ERCC1 rs11615 and lung cancer risk in a Chinese population

Haplotypes defined by multiple loci may be more precise and useful than genotypes in providing risk esti-mates for particular cancers. Diplotype is defined as a specific combination of two haplotypes. A Chinese case-control analysis comprising 370 cases and 388 controls was conducted to evaluate the effects of the high-risk diplotype predefined as PPP1R13L rs1970764AA-CD3EAP rs967591GG-ERCC1 rs11615AA among Caucasians and three SNPs alone or other haplotypes combined for lung cancer risk. Both the variant G-allele of PPP1R13L rs1970764 and the variant A-allele of CD3EAP rs967591 were significantly over-represented among cases (P = 0.03 and P = 0.002, respectively). The variant GG-homozygotes of PPP1R13L rs1970764 had increased risk [GG versus AA: adjusted OR (95% CI) = 1.30 (1.04-1.62), P = 0.02]. The carri-ers of variant A-allele of CD3EAP rs967591 also presented increased risk [AA versus GG: adjusted OR (95% CI) = 1.40 (1.12-1.75), P = 0.004; AG versus GG: adjusted OR (95% CI) = 1.47 (1.05-2.07), P = 0.03 and AG + AA versus GG: adjusted OR (95% CI) = 1.26 (1.07-1.48), P = 0.005]. Interaction between CD3EAP rs967591 and smoking duration was observed (P = 0.003). Only haplotype 1 (the common haplotype) defined as PPP1R13L rs1970764G-CD3EAP rs967591A-ERCC1 rs11615G showed marginally increased risk [OR (95% CI) = 1.38 (1.09-1.75), P = 0.009] after Bonferroni correction. The frequency of the high-risk diplotype predefined among Caucasians was 1% in controls and no significant evidence of the diplotype distribution between cases and controls was detected in present study. In conclusion, we found that vari-ant alleles of PPP1R13L rs1970764 and CD3EAP rs967591 may contribute to risk factors of lung cancer, but the high-risk diplotype predefined among Caucasians was rare and the diplotype is unlikely to confer lung cancer risk in a Chinese population.