AUTHOR=Liu Yongshi , Liang Xiaohua , Zhang Hongpei , Dong Jiajia , Zhang Yan , Wang Juan , Li Chunmei , Xin Xiangbing , Li Yan 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.938787

DOI=10.3389/fgene.2022.938787

ISSN=1664-8021

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