PDCD1 gene polymorphisms as regulators of T‐lymphocyte activity in cutaneous melanoma risk and prognosis

Abstract

This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627 + 252C>T), PD1.5 (c.804C>T), and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects, and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89-fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 versus 1.28 arbitrary units, p = .03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4 lymphocytes (16.6 versus 12.5%, p = .01; 17.0 versus 13.1%, p = .006). At 60 months of follow-up, short recurrence-free survival was seen in patients with PD1.1 AA genotype (33.3 versus 71.8%, p = .03). Patients with PD1.1 AA and PD1.5 CC genotype had 4.21 and 2.62 more chances of presenting relapse and evolving death by disease in Cox analyses, respectively. Our data provide preliminary evidence that abnormalities in regulation of T lymphocyte alter CM risk, clinical aspects, and prognosis.

Association between PD-1 and PD-L1 Polymorphisms and the Risk of Cancer: A Meta-Analysis of Case-Control Studies

“…Both PD-1 and PD-L1 are polymorphic. Several studies investigated the association between genetic polymorphisms of PD-1 and PD-L1 genes and the risk of various cancers, but the finding are still inconclusive [5,6,7,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52]. Thus, we performed a comprehensive meta-analysis in order to study the association of polymorphisms in PD-1 (rs2227981, rs2227982, rs11568821, rs7421861, rs36084323, and rs10204525) and PD-L1 (rs4143815, and rs2890658) with the risk of cancer.…”

Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population

“…The diagnosis of CM was established by histopathological evaluation of tumor fragments embedded in paraffin and stained with hematoxylin and eosin. Pathological aspects of the tumor (tumor location, histological type, Breslow thickness, Clark level, and tumor stage) were obtained from medical records of patients 25 . Tumor stage was identified using the TNM classification of the American Joint Committee on Cancer, where T describes the size of tumor, N describes spread of tumor to nearby lymph nodes, and M describes distant metastasis 2 .…”

“…The Hardy–Weinberg equilibrium (HWE) was tested using chi-square (χ 2 ) statistics for the goodness-to-fit test, and logistic regression model served to obtain age, skin color, sun exposure, and number of nevi status-adjusted crude odds ratios (ORs) with 95% confidence intervals (CI) in comparisons evolving patients and controls for study’s stage 2. To evaluate the robustness of risk estimates, the false discovery rate (FDR) was computed, which reflects the expected ratio of false-positive findings to the total number of significant findings; the differences revealed were considered statistically significant at FDR values < 0.05 25 . χ 2 and Fisher’s exact tests were used to evaluate associations between clinicopathological features and genotypes of selected SNVs.…”

“…The melanoma-specific survival (MSS) was calculated from the date of diagnosis until the date of death by the disease or last follow-up. PFS and MSS were calculated using Kaplan–Meier estimates, and differences between survival curves were analyzed by log-rank test 25 . The impact of age at diagnosis, gender, tumor location, Breslow thickness 37 , Clark level, TNM stage and genotypes of each analyzed SNV in survival of patients were evaluated using univariate Cox proportional hazards ratio (HR) regression.…”

“…At a second time, all variables with p < 0.20 were included in the multivariate Cox regression. The significant results of Cox analysis were internally validated using a bootstrap resampling study to investigate the stability of risk estimates (1,000 replications) 25 .…”