ER Stress-Related Genes EIF2AK3, HSPA5, and DDIT3 Polymorphisms are Associated With Risk of Lung Cancer

Objective: This study aimed to evaluate the associations between endoplasmic reticulum (ER) stress-related genes EIF2AK3/PERK, HSPA5/GRP78, and DDIT3/CHOP polymorphisms and the risk of lung cancer.Methods: Six single-nucleotide polymorphisms (SNPs) of EIF2AK3, HSPA5, and DDIT3 were genotyped in 620 cases and 620 controls using a MassARRAY platform.Results: The minor allele A of rs6750998 was a protective allele against the risk of lung cancer (p < 0.001), while the minor alleles of rs867529, rs391957, and rs697221 were all risk alleles that may lead to multiplied risk of the disease (rp(rs867529) = 0.002; p(rs391957) = 0.015; p(rs697221) < 0.001). Moreover, the rs6750998-TA/AA genotypes were protective genotypes against the risk of lung cancer (p = 0.005); however, the rs867529-GC/CC, rs391957-CC, and rs697221-GA/AA genotypes were associated with elevated lung cancer risk (p(rs867529) = 0.003, p(rs391957) = 0.028, and p(rs697221) = 0.0001). In addition, EIF2AK3-rs6750998 was associated with a decreased risk of lung cancer under dominant, recessive, and log-additive models (p < 0.05). By contrast, the EIF2AK3-rs867529 was correlated with an increased risk of the disease under dominant and log-additive models (p = 0.001). Moreover, HSPA5-rs391957 was related to an elevated risk of the disease under recessive and log-additive models (p < 0.02). DDIT3-rs697221 was identified to have a significant association with the risk of lung cancer under all three genetic models (p < 0.01).Conclusion: Our results provide new insights on the role of the ER stress-related genes EIF2AK3, HSPA5, and DDIT3 polymorphisms for lung cancer risk.

Automated summary

This study found associations between polymorphisms of EIF2AK3, HSPA5, and DDIT3 genes and the risk of lung cancer. The A allele of rs6750998 was shown to be a protective allele, while the minor alleles of rs867529, rs391957, and rs697221 were all risk alleles. Different genotypes were associated with an increased or decreased risk of lung cancer.