Interaction between common variants of and and and SNPs in relation to lung cancer risk among Chinese.

BACKGROUND

Lung cancer is a complex disease that diagnosed the most common cancer and led cause of cancer death. (MDM2 proto-oncogene) encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as TP53, for proteasomal degradation. Epidemiology studies have investigated the association of single nucleotide polymorphisms (SNP) and interaction between genetic and environmental factors with lung cancer.

METHODS

This Chinese case-control study comprised 627 cases and 633 controls explored the role of five htSNPs (rs1690924, rs1846402, rs2291857, rs3730581 and rs3730635, haplotype-tagging SNP) tagging 95% of the common haplotypes across the gene and the interactions of , , and in the same pathological pathway on lung cancer risk, together with smoking-duration.

RESULTS

None of the htSNPs in were associated with lung cancer risk in co-dominant, dominant, recessive, and log-additive models (adjusted for smoking-duration). Haplotype analysis showed that global haplotype association was statistically significant (P=0.0036, adjusted for smoking-duration) and haplotype5 (rs1690924-rs1846402-rs2291857-rs3730581-rs3730635) was associated with reduced risk of lung cancer [OR (95%) =0.52 (0.33-0.82), P=0.0053, adjusted for smoking-duration]. MDR interaction analysis showed that two the best significant models and strong synergy between and .

CONCLUSIONS

five-htSNPs haplotype exhibited association with lung cancer susceptibility, interaction of and htSNPs and smoking-duration contributed to lung cancer risk and strong synergy between and htSNPs influenced lung cancer predisposition. Our results suggest that , and smoking-duration interact in relation to lung carcinogenesis.