Dataset Information

A Single Nucleotide Polymorphism in HPGD Gene Is Associated with Prostate Cancer Risk.

ABSTRACT: Introduction: The HPGD gene was associated with some cancers, such as colorectal, breast, prostate, and bladder. However, detailed role of 15-hydroxyprostaglandin dehydrogenase (HPGD) gene remain unclear in prostate cancer. The study was to investigate the correlation between rs8752 that located in the 3'untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and prostate cancer (PCa) risk. Materials and Methods: 109 patients from the First Affiliate Hospital of Soochow University were recruited. According to the results of pathologic diagnosis, all patients were divided into two groups (prostate cancer and benign prostatic hyperplasia). The single-nucleotide polymorphism (SNP) rs8752 was genotyped in all samples by direct sequencing. Results: 54 prostate cancer and 55 BPH patients were included with a median age of 70.41 and 67.62 years, respectively. No statistically significant difference between two groups in patient criteria. The frequency of the GG homozygote and AG+GG genotype were 37.74% and 62.26% in 54 prostate cancer samples, while in 55BPH patients, values were 62.50% and 37.50%. Compared with the GG genotype, the combined GA+AA genotypes had a significantly higher risk of prostate cancer (OR = 2.750; 95% CI: 1.266-5.971, p = 0.011). Furthermore, the risk effect was obtained in subgroups of PCa patient group, the AA+AG genotypes significantly associated with the higher Gleason score samples (AA+AG vs GG: OR = 3.50, 95%CI = 1.106-11.072, p = 0.033) and the risk of pathological stage (AA+AG vs GG: OR = 4.00, 95%CI = 1.253-12.767, p = 0.019). Conclusions: rs8752 in the 3'untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene was found to be responsible for the susceptibility to prostate cancer in Chinese individuals.

SUBMITTER: Qi X

PROVIDER: S-EPMC5706011 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Single Nucleotide Polymorphism in HPGD Gene Is Associated with Prostate Cancer Risk.

Qi Xiaofei X Wang Yu Y Hou Jianquan J Huang Yuhua Y

Journal of Cancer 20171024 19

Introduction: The HPGD gene was associated with some cancers, such as colorectal, breast, prostate, and bladder. However, detailed role of 15-hydroxyprostaglandin dehydrogenase (HPGD) gene remain unclear in prostate cancer. The study was to investigate the correlation between rs8752 that located in the 3'untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and prostate cancer (PCa) risk. Materials and Methods: 109 patients from the First ...[more]

PMID: 29187884

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Project description:Myxovirus (influenza virus) resistance A (MxA) is an interferon stimulated antiviral protein that is required for a complete antiviral response. MxA polymorphism (rs2071430) is located within an Interferon Stimulated Response Element (ISRE) at position -88 in the gene's promoter region, and it has been associated with increased susceptibility to infections and various diseases. In general, the low promoter activity genotype (GG) promotes susceptibility, whereas the high promoter activity genotype (TT) confers protection to Hepatitis C viral infection. MxA's role in prostate cancer is not fully understood. Previous literature has shown that MxA may be a mediator of the effect of IFN on normal and tumor cell motility. MxA may act as a tumor suppressor and the level of expression may be a predictor of metastatic potential. Based on this information, in this study we investigated the association of this functional polymorphism (rs2071430) in MxA with prostate cancer.Sample size and power was calculated using the PGA software. Genomic DNA from a controls (n=140) and prostate cancer patients (n=164) were used for genotyping SNP rs2071430 on all samples. Statistical analysis was performed using logistic regression model.A significant association was observed between rs2071430 genotype GG and prostate cancer. Individuals harboring the GG genotype are at an increased risk of prostate cancer. Data stratification reveals that the mutant GT genotype offers either offers some protection against prostate cancer in Caucasians.MxA SNP rs2071430 GG genotype is significantly associated with prostate cancer irrespective of race. However, data stratification also suggests that the GT genotype is under-represented in Caucasian subjects suggesting its role in protection against prostate cancer in Caucasians. Although MxA is primarily implicated in viral infection, but it may be also be associated with prostate cancer. Recent studies have implicated viral and bacterial infections with increased prostate cancer risk. Expression of the high promoter activity genotype may offer resistance to prostate cancer infection and possibly influence clinical outcomes.

Project description:Importance:Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis. Objectives:To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification. Design, Setting, and Participants:A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019. Interventions:A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (<0.50), average (0.50-1.49), and high (≥1.50). Main Outcomes and Measures:Prostate cancer diagnosis-free survival among men of different risk groups. Results:Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (χ2 = 53.3; P < .001 for trend) and in participants with a negative FH of PCa (χ2 = 45.5; P < .001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to >80 years) for men at average genetic risk, and more than 80 years (95% CI, >80 to >80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH. Conclusions and Relevance:This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies.

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A Single Nucleotide Polymorphism in HPGD Gene Is Associated with Prostate Cancer Risk.

Publications

A Single Nucleotide Polymorphism in <i>HPGD</i> Gene Is Associated with Prostate Cancer Risk.

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