Shi Xiaoshun, Young Sylvia, Morahan Grant
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, 6 Verdun Street, Nedlands, Perth, WA 6009, Australia.
Cancers (Basel). 2021 Dec 20;13(24):6379. doi: 10.3390/cancers13246379.
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.
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.
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.
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.
肺癌的发病率在男性和女性之间存在差异，这表明性别特异性影响在这种癌症的易感性中可能发挥作用。虽然行为差异可能解释部分风险，但另一种可能性是X染色体上的易感基因可能产生影响。对于X染色体上导致性别特异性肺癌风险的基因变异知之甚少，因此我们在一个先前已表征的队列中对此进行了研究。
我们对518例肺癌患者和844例对照进行了基因关联再分析，以检测X染色体上的肺癌易感变异。还进行了注释基因表达、共表达分析、通路分析和免疫浸润分析。
24个单核苷酸多态性（SNP）被确定与男性肺癌病例显著相关，而与女性肺癌病例无关。这些SNP位于注释基因 、 和 附近的区域。其中， 在癌症基因组图谱中整理的肺癌病例中差异表达。对共表达基因的功能富集和KEGG通路分析表明，免疫功能差异可能在性别特异性易感性中起作用。
我们的分析确定了与性别特异性肺癌风险相关的潜在基因变异。整合全基因组关联研究（GWAS）和RNA测序数据揭示了肺癌预防的潜在靶点。
