Work

Polygenic risk scores associated with tumor immune infiltration in common cancers

Year: 2022

Type: preprint

Abstract: Purpose It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRS) and tumor immune infiltration in common cancers. Methods We constructed PRS for common cancers using the risk variants identified in previous genome-wide association studies. We analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied multivariable regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by intrinsic molecular subtypes for breast cancer and stage. Results We included 2,160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (P < 0.05) significance level, we identified 31 significant associations between PRS and immune traits in prostate cancer (14), colorectal cancer (5), breast cancer (4), lung squamous cell carcinoma (4), lung adenocarcinoma (2), ovarian cancer (1), and pancreatic cancer (1). In the analyses stratified by intrinsic molecular subtypes for breast cancer, we identified 35 significant associations, including 31 associations that were undetected by the overall analysis. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. Conclusions This study shows the evidence of PRS affecting immune infiltration and provides novel insights into the role of genetic susceptibility in the immune responses underlying cancer development and prognosis.

Source: Research Square

DOI: 10.21203/rs.3.rs-1796640/v1