Association Between Three Polymorphisms in BMAL1 Genes and Risk of Lung Cancer in a Northeast Chinese Population

Abstract

The connection between cancer and circadian rhythms has garnered recent attention. BMAL1 is a core factor in the regulation of circadian rhythms, and its variants have frequently been associated with human diseases, including cancer. Our study first clarifies the relationship of three single-nucleotide polymorphisms (rs3816360, rs2290035, and rs3816358) in BMAL1 with the risk of lung cancer, as well as the gene–environment interaction between the polymorphisms and tobacco exposure in a Northeast Chinese population. A case–control study of 409 new diagnosis patients and 417 controls was performed in Shenyang, Liaoning province. The gene–environment interactions were explored on both additive and multiplicative scale. After Bonferroni correction, rs3816360 and rs2290035 were evidently associated with lung cancer risk. For rs3816360, subjects carrying CC (adjusted odds ratio [OR] = 2.163, 95% confidence interval [CI] = 1.413–3.310, p = 0.004) genotype showed an increased risk of lung cancer compared to the subjects carrying homozygous TT genotype. As for rs2290035, homozygous carriers of AA genotype (OR = 1.908, 95% CI = 1.207–3.017, p = 0.006) showed a significantly increased risk of lung cancer. The dominant models and recessive models of rs3816360 and rs2290035 showed significant associations (p < 0.01). In the stratified analysis, our results revealed that rs3816360 and rs2290035 were associated with the risk of lung adenocarcinoma. However, rs3816358 polymorphism was not significantly associated with lung cancer risk. The measures of additive interaction and logistic models suggested that the gene–environment interactions were not statistically significant on both additive and multiplicative scales.