Dataset Information

Association study between genetic variants in retinol metabolism pathway genes and prostate cancer risk.

ABSTRACT:

Background

Evidence suggests that serum retinol level is associated with prostate cancer risk, but the association between genetic variants in the retinol metabolism pathway genes and prostate cancer risk remains unclarified.

Methods

Single-nucleotide polymorphisms (SNPs) in 31 genes in the retinol metabolism pathway were genotyped to evaluate the association with prostate cancer risk in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The gene expression analysis was evaluated using data from the Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database. Data from the Genotype-Tissue Expression (GTEx) project dataset were utilized to perform the expression quantitative trait loci (eQTL) analysis.

Results

Two SNPs were significantly associated with prostate cancer risk [rs1330286 in ALDH1A1: odds ratio (OR) = 0.88, 95% confidence interval (CI) = 0.83-0.94, p = 2.45 × 10^-4 ; rs4646653 in ALDH1A3: OR = 1.17, 95% CI =1.07-1.27, p = 4.33 × 10^-4 ]. Moreover, the mRNA level of ALDH1A3 was significantly higher in prostate cancer tissues than in normal tissues in both TCGA datasets and GEO datasets (p = 1.63 × 10^-12 and p = 4.33 × 10^-2 , respectively). rs1330286 was an eQTL of ALDH1A1 (P = 2.90 × 10^-3 ).

Conclusion

Our findings highlight that genetic variants in retinol metabolism pathway genes are associated with prostate cancer risk.

SUBMITTER: Cao D

PROVIDER: S-EPMC7774741 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Association study between genetic variants in retinol metabolism pathway genes and prostate cancer risk.

Cao Dongliang D Meng Yixuan Y Li Shuwei S Xin Junyi J Ben Shuai S Cheng Yifei Y Wang Meilin M Hua Lixin L Cheng Gong G

Cancer medicine 20201017 24

<h4>Background</h4>Evidence suggests that serum retinol level is associated with prostate cancer risk, but the association between genetic variants in the retinol metabolism pathway genes and prostate cancer risk remains unclarified.<h4>Methods</h4>Single-nucleotide polymorphisms (SNPs) in 31 genes in the retinol metabolism pathway were genotyped to evaluate the association with prostate cancer risk in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer S ...[more]

PMID: 33068330

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Project description:BackgroundAlthough the sphingolipid metabolism pathway is known to play a significant role in tumor progression, there have been few studies on how genetic variants in the sphingolipid metabolism pathway genes affect the survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).MethodsWe utilized available genotyping data to conduct multivariate Cox proportional hazards regression model analysis, examining the associations of 12,188 single nucleotide polymorphisms (SNPs) in 86 sphingolipid metabolism pathway genes on the survival of 866 HBV-HCC patients, and the model was also used in additive interaction analysis. We used bioinformatics functional prediction and expression quantitative trait locus (eQTL) analysis to explore the potential functions of SNPs and to evaluate the association of SNPs with the corresponding mRNA expression, respectively. We also used the online database TIMER2.0 (http://timer.comp-genomics.org/) to analyze the relationship between the corresponding mRNA expression levels and immune cell infiltration.ResultsOur study found that GBA2 rs1570247 G>A was significantly associated with elevated survival of HBV-HCC patients [(hazards ratio (HR)=0.74, 95% confidence interval (CI)=0.64-0.86, P<0.001)]. And on an additive scale, a synergistic effect was observed between the GG genotype of rs1570247 and advanced BCLC stage. Among HBV-HCC patients with advanced BCLC stage, those carrying the GBA2 rs1570247 GG genotype exhibited a significantly elevated risk of mortality (HR=3.32, 95%CI=2.45-4.50). Further functional prediction and eQTL analysis revealed that rs1570247 were located in the 5' untranslated region of the GBA2, the A allele of SNP rs1570247 was associated with higher mRNA expression levels of GBA2 in normal liver tissues (P=0.009). Moreover, we observed a positive correlation between GBA2 mRNA expression and the infiltration level of B lymphocytes cell (R=0.331, P<0.001), while a negative correlation was noted between GBA2 mRNA expression and the infiltration level of macrophage M2 in HCC (R=-0.383, P<0.001).ConclusionOur findings suggest that GBA2 rs1570247 G>A in sphingolipid metabolism pathway may be a key factor for survival of HBV-HCC patients by regulating the expression of corresponding genes and affecting the infiltration level of immune cells.

Dataset Information

Association study between genetic variants in retinol metabolism pathway genes and prostate cancer risk.

Background

Methods

Results

Conclusion

Publications

Association study between genetic variants in retinol metabolism pathway genes and prostate cancer risk.

Similar Datasets

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