Cuproptosis-Related Gene - and - Polymorphisms are Associated with Risk of Lung Cancer.

BACKGROUND

Cuproptosis is a novel copper-dependent cell death, and the copper level was increased in lung cancer patients. However, few studies evaluated the association between single-nucleotide polymorphisms (SNPs) in cuproptosis-related genes and lung cancer risk.

METHODS

Six SNPs of the and genes were genotyped in a case-control cohort including 650 lung cancer cases and 650 controls using the MassARRAY platform.

RESULTS

The minor alleles of -rs10981694 and -rs10488764 were associated with an increased risk of lung cancer (rs10981694: OR=1.455, 95% CI: 1.201-1.763, <0.001; rs10488764: OR=1.483, 95% CI: 1.244-1.768, <0.001). In contrast, the minor alleles of rs9535826 and rs9535828 in were related to a decreased risk of the disease (rs9535826: OR=0.714, 95% CI: 0.608-0.838 <0.001; rs9535828: OR=0.679, 95% CI: 0.579-0.796, <0.001). The frequencies of rs10981694-TG/GG and rs10488764-GA/AA genotypes were significantly higher in lung cancer cases than that in controls, making them risk genotypes for the disease ( < 0.001); while the rs9535826-TG/GG and rs9535828-GA/AA genotypes were protective genotypes and associated with a reduced risk of the disease (<0.001). Genetic model evaluation revealed that -rs10981694 and -rs10488764 were associated with a growing risk of lung cancer in dominant, recessive and log-additive models (<0.001). Moreover, rs9535826 and rs9535828 in were related to a declining risk of the disease in three genetic models (<0.001). In addition, stratification analysis showed that -rs10488764 was risk variant for lung cancer in both smokers and nonsmokers, and was associated with risk of each pathological type of lung cancer (<0.008).

CONCLUSION

The results shed new light on the correlation between cuproptosis-related genes and risk of lung cancer.