LAUSR

Simple Summary Polygenic risk scores (PRSs) have been used to predict the risk of developing cancer. However, whether PRSs are associated with immune infiltration in solid tumors remains unclear. We constructed PRSs for common cancers of the breast, colorectum, lung, ovary, pancreas, and prostate using risk variants identified in previous genome-wide association studies, and comprehensively evaluated their associations with 139 immune traits previously estimated from The Cancer Genome Atlas. We identified 31 significant associations between PRSs and immune traits at a nominal (p < 0.05) level of significance. In the analyses stratified by stage for breast cancer, colorectal cancer, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. Our findings provide novel insights into the role of genetic susceptibility in the immune responses underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy. Abstract It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, 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 regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 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 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. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.