Association Analysis Of DCLRE1B Single Nucleotide Polymorphism (Rs11552449) With Prostate Cancer Risk In Guangzhou Han Population

Background:Prostate cancer(PCa)is one of the most common malignancies in the male genitourinary system.The risk factors of its onset remain to be well understood.At present,age,racial background,family history and genetic susceptibility are considered as endogenous risk factors.In addition,environmental and dietary factors may also be related to the risk of PCa.Genetic susceptibility plays an essential role in the occurrence of PCa.Single nucleotide polymorphisms(SNPs)are one of the important material foundations of genetic susceptibility.To date,more than 100 common susceptibility loci have been identified through genome-wide studies.SNPs are widely distributed in the population,and this genetic marker has high stability,so genetic analysis can be performed decades before individual onset.Therefore,SNPs may not only provide an effective method to discover and validate the genetic etiology of tumorigenesis,but also become a potential tool for cancer screening.Purpose:This study was designed to explore the association of DCLRE1B SNP rs11552449(a non-synonymous SNP)with the risk of PCa in Guangzhou Han population.Methods:This study was a hospital-based case-control study approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University.From January 2015 to April 2018,blood samples of 334 patients with PCa and 304 cancer-free patients or healthy people were collected from Zhujiang Hospital of Southern Medical University.DCLRE1B gene was genotyped by SNaPshot method.The deviation of genotype distribution from the Hardy-Weinberg equilibrium was verified by Chi-square(χ2)test.In stratification analyses,age at diagnosis(≤70 and>70 years)and tumor aggressiveness(both the localized and advanced cases)were used as stratified factors to analyze the relationship between specific genotype(or allele)and the risk of PCa.Localized and advanced PCa were classified according to the following criteria(localized PCa:T1-2N0M0,Gleason score ≤7,and PSA levels ≤50 ng/mL;advanced PCa:T3-4 or N+or M+or Gleason score 8-10 or PSA levels>50 ng/mL).Logistic regression analysis was used to calculate odds ratios(ORs),95%confidence intervals(CIs),and P values for the association between PCa risk and genotype(or alleles).For logistic regression analysis,age,smoking history and drinking history were taken as confounding factors to calculate adjusted odds ratios(AORs),95%CIs and P value.All the statistical analyses were performed with IBM SPSS Statistic(version 20.0)while the P value of<0.05 was regarded to be statistically significant(two-tailed).Results:There was no significant difference in age,smoking status and drinking status compositions between case group and control group(P>0.05).The genotype frequency of DCLRE1B SNP rs 11552449 in control group maintained Hardy-Weinberg equilibrium(P>0.05).Compared with DCLRE1B SNP rs11552449 CC genotype,patients with CT genotype had a higher risk of PCa(AOR=1.533,95%CI=1.095～2.145,P=0.013)between case group and control group.For the tumor aggressiveness stratification analysis,when the localized PCa subgroup was compared with the control group(cancer-free patients or healthy men),carriers of the TT genotype were at higher risk of localized PCa than those of the CC genotype(AOR=2.332,95%CI=1.174～4.634,P=0.016);in the advanced PCa subgroup,CT genotype carriers had an increased risk of advanced PCa than CC genotype carriers(AOR=1.561,95%CI=1.078～2.259,P=0.018).For people ≤70 years old,CT genotype was also related to a higher risk of PCa(AOR=2.390,95%CI=1.437～3.973,P=0.001);for people over 70 years old,there was no significant association between rs11552449 and PCa risk.Conclusion:This case-control study has demonstrated that the CT genotype of DCLRE1B SNP rs11552449 increases the risk of PCa in Guangzhou Han population.