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Single-Nucleotide Polymorphisms in Vitamin D-Related Genes May Modify Vitamin D-Breast Cancer Associations.

ABSTRACT: Background: We previously observed that high serum 25-hydroxyvitamin D (25(OH)D; >38.0 ng/mL) was inversely associated with breast cancer. Here, we examined effect modification by SNPs in vitamin D-related genes.Methods: The Sister Study enrolled 50,884 U.S. women who had a sister with breast cancer, but who had never had breast cancer themselves. Using a case-cohort design, we compared 1,524 women who developed breast cancer within 5 years to 1,810 randomly selected participants. We estimated ratios of HRs (RHRs) for the 25(OH)D-breast cancer association per copy of the minor allele using Cox proportional hazards models. We considered 82 SNPs in 7 vitamin D-related genes (CYP24A1, CYP27B1, CYP2R1, GC, DHCR7/NADSYN1, RXRA, and VDR). We also tested gene-based interactions with 25(OH)D.Results: The SNP with the smallest interaction P value was rs4328262 in VDR (P = 0.0008); the 25(OH)D HR was 0.92 [95% confidence interval (CI), 0.68-1.24] among those homozygous for the common allele, and the minor allele was estimated to decrease the HR by 33% per copy (RHR = 0.67; 95% CI, 0.53-0.85). Five other VDR SNPs showed evidence of interaction at P < 0.05, as did one SNP in CYP2R1 and one in RXRA As a group, the 82 SNPs showed evidence of multiplicative interaction with 25(OH)D (P = 0.04). In gene-based tests, only VDR showed strong evidence of interaction (P = 0.04).Conclusions: SNPs in vitamin D-related genes may modify the association between serum 25(OH)D and breast cancer.Impact: This work strengthens the evidence for protective effects of vitamin D. Cancer Epidemiol Biomarkers Prev; 26(12); 1761-71. ©2017 AACR.

SUBMITTER: O'Brien KM

PROVIDER: S-EPMC5906103 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Single-Nucleotide Polymorphisms in Vitamin D-Related Genes May Modify Vitamin D-Breast Cancer Associations.

O'Brien Katie M KM Sandler Dale P DP Kinyamu H Karimi HK Taylor Jack A JA Weinberg Clarice R CR

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20171025 12

<b>Background:</b> We previously observed that high serum 25-hydroxyvitamin D (25(OH)D; >38.0 ng/mL) was inversely associated with breast cancer. Here, we examined effect modification by SNPs in vitamin D-related genes.<b>Methods:</b> The Sister Study enrolled 50,884 U.S. women who had a sister with breast cancer, but who had never had breast cancer themselves. Using a case-cohort design, we compared 1,524 women who developed breast cancer within 5 years to 1,810 randomly selected participants. ...[more]

PMID: 28830874

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Project description:PurposeTumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated.Patients and methodsPeripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis.ResultsA total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule.ConclusionThe polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.

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Single-Nucleotide Polymorphisms in Vitamin D-Related Genes May Modify Vitamin D-Breast Cancer Associations.

Publications

Single-Nucleotide Polymorphisms in Vitamin D-Related Genes May Modify Vitamin D-Breast Cancer Associations.

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