Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Abstract

BackgroundRegulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.MethodsIn a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.ResultsThe most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with (p = 0.001) and clear cell EOC. Gene associations with histotypes at< 0.05 included:(p = 0.005 and = 0.008, serous and high-grade serous, respectively), (p = 0.035, endometrioid and mucinous), (p = 0.03, mucinous), (p = 0.022, clear cell), (p = 0.021 endometrioid) and (p = 0.017 and = 0.025, endometrioid and mucinous, respectively).ConclusionsCommon inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival

“…SNP selection and quality control were performed as previously described, yielding a total of 736 SNPs for analyses [4]. We calculated the effective number of independent SNPs tested; this value was used in a Bonferroni correction to determine single SNP significance [4].…”

“…SNP selection and quality control were performed as previously described, yielding a total of 736 SNPs for analyses [4]. We calculated the effective number of independent SNPs tested; this value was used in a Bonferroni correction to determine single SNP significance [4]. We utilized Cox proportional hazards regression models adjusted for age, tumor stage and grade to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing SNP associations with EOC overall and by invasive histotype.…”

Algorithms Used in Ovarian Cancer Detection: A Minireview on Current and Future Applications

“…Current studies are analyzing inflammatory markers, circulating miRNAs, circulating cell-free DNA and tumor cells, autoantibodies, and nanotechnology. Hampras et al has shown modest gene associations between TGFBR2 and clear-cell EOC, providing evidence for an immune component for carcinogenesis (45). Eo Overall, ovarian cancer screening is not recommended at this time as it has not shown a mortality benefit and increases harm.…”