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

Abstract

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 (r p 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.