Identification of Genetic Variants Associated with Sex-Specific Lung-Cancer Risk.

BACKGROUND

The incidence of lung cancer differs between men and women, suggesting the potential role of sex-specific influences in susceptibility to this cancer. While behavioural differences may account for some of the risk, another possibility is that X chromosome susceptibility genes may have an effect. Little is known about genetic variants on the X chromosome that contribute to sex-specific lung-cancer risk, so we investigated this in a previously characterized cohort.

METHODS

We conducted a genetic association reanalysis of 518 lung cancer patients and 844 controls to test for lung cancer susceptibility variants on the X chromosome. Annotated gene expression, co-expression analysis, pathway, and immune infiltration analyses were also performed.

RESULTS

24 SNPs were identified as significantly associated with male, but not female, lung cancer cases. These resided in blocks near the annotated genes , , and .. Of these, was differentially expressed in lung cancer cases curated in The Cancer Genome Atlas. A functional enrichment and a KEGG pathway analysis of co-expressed genes revealed that differences in immune function could play a role in sex-specific susceptibility.

CONCLUSIONS

Our analyses identified potential genetic variants associated with sex-specific lung cancer risk. Integrating GWAS and RNA-sequencing data revealed potential targets for lung cancer prevention.