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Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D3 levels and survival among patients with metastatic colorectal cancer.

ABSTRACT: PURPOSE:The relationships of genetic variation in the vitamin D pathway with circulating 25-hydroxyvitamin D3 [25(OH)D] levels and survival remain largely unknown for patients with metastatic colorectal cancer (mCRC). METHODS:Among 535 patients participating in a randomized trial of chemotherapy for mCRC, we prospectively measured baseline plasma 25(OH)D and examined 124 tagging single-nucleotide polymorphisms (SNPs) within seven genes in the vitamin D pathway, including five SNPs associated with circulating 25(OH)D levels in previous genome-wide association studies (GWAS). We evaluated whether these SNPs were associated with plasma 25(OH)D levels and patient outcome (overall survival, time to progression, and tumor response), using linear, logistic, and Cox proportional hazards regression. RESULTS:We observed a significant association between 25(OH)D levels and an additive genetic risk score determined by the five GWAS-identified SNPs (p?=?0.0009). We did not observe any direct association between 25(OH)D-associated SNPs, individually or as a genetic risk score, and patient outcome. However, we found a significant interaction between 25(OH)D levels and rs12785878 genotype in DHCR7 on overall survival (pinteraction?=?0.02). CONCLUSION:Germline genetic variation in the vitamin D pathway informs baseline 25(OH)D levels among patients with mCRC. The association between 25(OH)D levels and overall survival may vary by DHCR7 genotype. ClinicalTrials.gov Identifier: NCT00003594 ( https://clinicaltrials.gov/ct2/show/NCT00003594 ).

SUBMITTER: Yuan C

PROVIDER: S-EPMC6639016 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D<sub>3</sub> levels and survival among patients with metastatic colorectal cancer.

Yuan Chen C Renfro Lindsay L Ambadwar Pratibha B PB Ou Fang-Shu FS McLeod Howard L HL Innocenti Federico F Meyerhardt Jeffrey A JA Wolpin Brian M BM Goldberg Richard M RM Grothey Axel A Fuchs Charles S CS Ng Kimmie K

Cancer causes & control : CCC 20190518 7

<h4>Purpose</h4>The relationships of genetic variation in the vitamin D pathway with circulating 25-hydroxyvitamin D<sub>3</sub> [25(OH)D] levels and survival remain largely unknown for patients with metastatic colorectal cancer (mCRC).<h4>Methods</h4>Among 535 patients participating in a randomized trial of chemotherapy for mCRC, we prospectively measured baseline plasma 25(OH)D and examined 124 tagging single-nucleotide polymorphisms (SNPs) within seven genes in the vitamin D pathway, includin ...[more]

PMID: 31104167

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Project description:BackgroundVitamin D status has been associated with the presence and severity of several premenstrual symptoms (PMSx) in some, but not all studies. Inconsistencies among findings may be explained by unaccounted genetic variation in the vitamin D receptor (VDR).ObjectiveTo determine whether associations between vitamin D status and individual PMSx are influenced by VDR genotype.MethodsSeven hundred sixteen women aged 20-29 years old from the Toronto Nutrigenomics and Health study provided plasma samples and completed a questionnaire on the presence and severity of 15 common PMSx. Plasma 25-hydroxyvitamin D (25(OH)D) concentration was measured and participants were categorized into sufficient (≥ 50 nmol/L) and insufficient (< 50 nmol/L) vitamin D status groups. DNA was obtained from blood samples to genotype for a common VDR single nucleotide variant, rs796858. Using logistic regression, odds of experiencing PMSx were compared between vitamin D-sufficient and insufficient women, stratified by genotype.ResultsAmong CC homozygotes, insufficient vitamin D status was associated with higher odds of experiencing premenstrual fatigue (OR, 2.53; 95% CI, 1.40, 4.56) and nausea (OR, 2.44; 95% CI, 1.00, 5.95). Among TT homozygotes, insufficient vitamin D status was associated with lower odds of experiencing fatigue (OR, 0.44; 95% CI, 0.20, 0.97) and increased appetite (OR, 0.48; 95% CI, 0.22, 1.04). Insufficient vitamin D status was associated with higher odds of increased appetite in women with the CT genotype (OR, 1.78; 95% CI, 1.03, 3.07). VDR genotype modified the association between vitamin D status and the following PMSx: increased appetite (interaction p = 0.027), fatigue (interaction p = 0.016), and nausea (interaction p = 0.039).ConclusionWe found evidence that VDR genotype may modify the association between 25(OH)D and some PMSx. Insufficient 25(OH)D was associated with a higher risk of premenstrual fatigue in those with the CC genotype, but lower risk in those with the TT genotype.

Dataset Information

Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D3 levels and survival among patients with metastatic colorectal cancer.

Publications

Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D<sub>3</sub> levels and survival among patients with metastatic colorectal cancer.

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