Genetic polymorphisms of FCGR2A, ORAI1 and CD40 are associated with risk of lung cancer.

Abstract

FCGR2A, ORAI1 and CD40 are all involved in the immune and inflammatory responses in the human body, whereas its association with lung cancer is still unclear. This study aimed to investigate the effects of polymorphisms in these genes on the susceptibility to lung cancer. Six candidate single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a discovery cohort, including 400 lung cancer patients and 400 healthy controls, and validated in a replication cohort, including 529 lung cancer cases and 532 controls. Comparing the allele frequency distributions, we found that the rs1801274-G, rs511278-T and rs1883832-T were risk alleles for lung cancer (P < 0.05), whereas the minor allele of rs12320939-T was a protective allele for the disease (P = 0.037). Comparing the genotype frequency distributions, we found that rs1801274-GG, rs511278-CT and of rs1883832-TT were risk genotype for lung cancer (P < 0.05). Genetic model analysis showed that the rs1801274 A>G was correlated with an elevated risk of lung cancer in recessive and log-additive models (P < 0.05); rs511278 C>T exhibited an increased risk of disease in dominant and log-additive models (P < 0.05); rs1883832 C>T had a strong relationship with risk of disease in all three models (P < 0.001), whereas rs12320939 G>T was correlated to a reduced risk of disease in recessive and log-additive models (P < 0.05). Finally, the association between the above SNPs and lung cancer risk was validated in a replication cohort (P < 0.05). These results shed new light on the association between immune-related genes and risk of lung cancer, and might be useful for the identification of high-risk individuals.