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The toll‐like receptor (TLR) signaling pathway plays an important role in the innate immune responses and antigen‐specific acquired immunity. Aberrant activation of the TLR pathway has a significant impact on carcinogenesis or tumor progression. Therefore, we hypothesize that genetic variants in the TLR signaling pathway genes are associated with overall survival (OS) of patients with non‐small cell lung cancer (NSCLC). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate associations between genetic variants of 165 TLR signaling pathway genes and NSCLC OS using the genome‐wide association study (GWAS) dataset from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The results were further validated by the Harvard Lung Cancer Susceptibility GWAS dataset. Specifically, we identified IRAK2 rs779901 C > T as a predictor of NSCLC OS, with a variant‐allele (T) attributed hazards ratio (HR) of 0.78 [95% confidence interval (CI) = 0.67–0.91, P = 0.001] in the PLCO dataset, 0.84 (0.72–0.98, 0.031) in the Harvard dataset, and 0.81 (0.73–0.90, 1.08x10−4) in the meta‐analysis of these two GWAS datasets. In addition, the T allele was significantly associated with an increased mRNA expression level of IRAK2. Our findings suggest that IRAK2 rs779901 C > T may be a promising prognostic biomarker for NSCLC OS. What's new? Abnormal signaling by the toll‐like receptor (TLR) pathway, normally a crucial mediator of innate and antigen‐specific acquired immune responses, potentially favors tumor progression. Little is known, however, about associations between TLR signaling and patient outcome. In the present study, re‐analysis of existing genome‐wide association study datasets for patients with non‐small cell lung cancer (NSCLC) uncovered a prognostic variant in IRAK2 (rs779901 C > T), a gene encoding a receptor‐associated kinase in the TLR pathway. IRAK2 rs779901 C > T specifically predicted overall survival in NSCLC patients. While mechanistic study is needed, the findings suggest that the variant is a promising prognostic biomarker in NSCLC. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) is considered as a steroid hormone‐related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR‐related genes) in CM‐specific survival (CMSS). Here, we performed a pathway‐based analysis to evaluate genetic variants of 191 SHR‐related genes in 858 CMSS patients using a dataset from a genome‐wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS. Using multivariate Cox proportional hazards regression analysis, we identified three‐independent SNPs (RORA rs782917 G > A, RORA rs17204952 C > T and DNMT1 rs7253062 G > A) as predictors of CMSS, with a variant‐allele attributed hazards ratio (HR) and 95% confidence interval of 1.62 (1.25–2.09), 1.60 (1.20–2.13) and 1.52 (1.20–1.94), respectively. Combined analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose–response manner as the number of risk genotypes increased (ptrend < 0.001); however, no improvement in the prediction model was observed (area under the curve [AUC] = 79.6–80.8%, p = 0.656), when these risk genotypes were added to the model containing clinical variables. Our findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers for CMSS, but these results needed to be validated in future larger studies. [ABSTRACT FROM AUTHOR]

The platelet‐derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome‐wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05–1.16, and p = 4.70 × 10−5 for the rs5757573 C allele and 1.21, 1.11–1.32, and 2.01 × 10−5 for the rs6001516 T allele]. Haplotype analysis revealed that the C‐T haplotype carriers had a significantly increased risk of PC than those carrying the T‐C haplotype (OR = 1.23, 95% CI = 1.12–1.34, p =5.00 × 10−6). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1–2 NUGs, particularly among 60–70 age group or males, had an increased risk of PC, compared to those without NUG. Furthermore, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (p = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to PC. Further population and functional validations of our findings are warranted. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS. Using multivariate Cox proportional hazards regression analysis, we identified three-independent SNPs (RORA rs782917 G > A, RORA rs17204952 C > T and DNMT1 rs7253062 G > A) as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) and 95% confidence interval of 1.62 (1.25-2.09), 1.60 (1.20-2.13) and 1.52 (1.20-1.94), respectively. Combined analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (p trend  < 0.001); however, no improvement in the prediction model was observed (area under the curve [AUC] = 79.6-80.8%, p = 0.656), when these risk genotypes were added to the model containing clinical variables. Our findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers for CMSS, but these results needed to be validated in future larger studies., (© 2018 UICC.)