The Polymorphisms Of CARD8 And ANRIL With The Risk Of Lung Cancer

Objects: Lung cancer is one of the malignant tumors with high morbidity and mortality in many developing countries,and it is also one of the major diseases affecting the quality of human life.Studies have shown that rs7248320 may be a quantitative trait locus for CARD8 lncRNA AC008392.1.Studies have also shown that rs7248320 polymorphism is associated with susceptibility to hepatocellular carcinoma and cervical cancer.ANRIL is located in the short arm 21 region of chromosome 9,and ANRIL and CARD8 are co-expressed.The 9p21.3 mutation in the ANRIL intron region was associated with squamous cell lung cancer,and rs2151280 was located in the ANRIL intron region 9p21.3.The relationship between the two sites of CARD8 rs7248320 and ANRIL rs2151280 and lung cancer susceptibility has not been reported.This study was the first time to use a case-control study to investigate the relationship between CARD8 rs7248320 and ANRIL rs2151280 polymorphisms and lung cancer susceptibility in Northeast China.Methods: This study was a hospital-based case-control study.Taqman real-time PCR was used to determine the genotype of rs7248320 in 512 lung cancer patients and 588 controls,and to determine the genotype of rs2151280 in 507 lung cancer patients and 542 controls.The categorical variables(sex,smoking status,etc.)and continuous variables(age)in the cases and controls were analyzed by t-test and chi-square test,respectively.Logistic regression analysis calculated OR and its 95% confidence interval.The additive and multiplicative models were used to estimate the association of smoking status and genetic polymorphism with lung cancer susceptibility.The statistical analysis software used was SPSS 20.0.Results: Studies had shown that the rs7248320 polymorphism of CARD8 was associated with susceptibility to non-small cell lung cancer.Individuals carrying the homozygous GG genotype had a reduced risk of non-small cell lung cancer compared with individuals carrying the CARD8 rs7248320 homozygous wild AA genotype/heterozygous GA genotype(OR = 0.653,95% CI = 0.442-0.966,P = 0.033).Stratified by age,the CARD8 rs7248320 polymorphism was associated with the risk of lung cancer in people over 60 years of age.The interaction between rs7248320 polymorphism and smoking exposure was not found to have an impact on the risk of lung cancer.The rs2151280 polymorphism of ANRIL was associated with susceptibility to lung cancer,non-small cell lung cancer,and lung adenocarcinoma.Individuals carrying the CC genotype had a reduced risk of developing lung cancer compared with individuals carrying the TT genotype(OR = 0.640,95% CI = 0.421-0.972,P = 0.036).Individuals carrying the C allele had a reduced risk of non-small cell lung cancer(OR = 0.674,95% CI = 0.560-0.812,P < 0.001).Individuals carrying the CC genotype had a lower risk of developing lung adenocarcinoma than individuals carrying the TT genotype(OR=0.567,95% CI = 0.333-0.965,P = 0.037).No interaction between rs2151280 polymorphism of ANRIL and smoking exposure was found to have an impact on the risk of lung cancer.Conclusions: The rs7248320 polymorphism of CARD8 was associated with susceptibility to non-small cell lung cancer.The rs2151280 polymorphism of ANRIL was associated with susceptibility to lung cancer,non-small cell lung cancer and lung adenocarcinoma.The association between CARD8 rs7248320 and ANRIL rs2151280 polymorphisms in CARD8 and smoking exposure was not associated with lung cancer susceptibility.