ASPO Abstracts
Common genetic variations in the calcium sensing receptor (CaSR) gene, plasma 25-hydroxyviamin D and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP)
Category: Cancer Health Disparities
Conference Year: 2019
Abstract Body:
Purpose: We evaluated 29 functionally relevant and independent SNPs with minor allele frequency>0.05 in the calcium sensing receptor (CaSR) gene in relation to high aggressive prostate cancer and examined their interactions with plasma vitamin D levels among African-American (AA) and European-American (EA) men using data from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Methods: The sample consisted of 217 AAs and 187 EAs with histologically-confirmed diagnosis of high aggressive prostate cancer as cases, and 307 AAs and 470 EAs with low aggressive prostate cancers as the comparison group. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for high aggressive prostate cancer associated with each CaSR SNP. The cross-product of high- vs. low-level plasma 25(OH)D and continuous minor allele number of each CaSR SNP was added in the logistic regression model to assess the interaction.Results: Among AAs, the minor alleles of CaSRrs1501898 and CaSRrs13324814 were associated with 40% (OR=0.60, 95% CI=0.37-0.97) and 31% (OR=0.69, 95% CI=0.51-0.93) reduced odds of high aggressive prostate cancer, respectively, while CaSRrs2036399 minor allele increased high aggressive prostate cancer by 1.5-fold (OR=1.52, 95% CI=1.05-2.21). Among EAs, the only significant association was seen for the CaSRrs3863977 minor allele (OR=0.73, 95% CI=0.55-0.96). However, none of the SNPs reached statistical significance after adjusting for multiple testing using false discovery rate method. Among AAs, the minor allele of CaSRrs1354162 was associated with increased odds of high aggressive prostate cancer among subjects with low-level plasma 25(OH)D but not among subjects with high-level 25(OH)D (P-interaction=0.05). We did not observe any significant interaction effects between plasma 25(OH)D and SNPs among EAs. Conclusions: Three of 29 SNPs in the CaSR gene were found to be associated with high aggressive prostate cancer among AAs and one among EAs, but results were not statistically significant after adjusting for multiple testing. There was little evidence of interaction between CaSR SNPs and plasma 25(OH)D levels in relation to high aggressive prostate cancer in this racially diverse population-based study.
Keywords: prostate cancer, Vitamin D, SNPs, racial disparities