Association Between Three Polymorphisms In BMAL1 Genes And Risk Of Lung Cancer

Objective: 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 firstly clarifies the relationship of three SNPs(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.Methods: we conducted a case-control study in Shenyang,Liaoning province to examine the relationship of BMAL1 SNPs rs3816358,rs3816360,rs2290035 with lung cancer in a Northeast Chinese population.Stratified analyses were also conducted based on different histology types to further investigate the association between rs3816360,rs2290035,rs3816358 and risk of lung cancer.The gene–environment interactions were explored on both additive and multiplicative scale.Results: Results adjusted by age and gender showed that 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<0.05).In the stratified analysis,our results revealed that rs3816360 were associated with the risk of lung adenocarcinoma and lung squamous carcinoma risk,while 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.Conclusion: 1.the present study firstly reported that two SNPs(rs3816360,rs2290035)of BMALI may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in a Northeast Chinese population.However,rs3816358 polymorphism in BMAL1 was not associated with lung cancer risk.2.The gene–environment interaction between the polymorphisms in BMAL1 and tobacco exposure were not statistically significant on both additive and multiplicative scales.