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01-07-2019 | Colorectal Cancer | Original Paper

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

Authors: Chen Yuan, Lindsay Renfro, Pratibha B. Ambadwar, Fang-Shu Ou, Howard L. McLeod, Federico Innocenti, Jeffrey A. Meyerhardt, Brian M. Wolpin, Richard M. Goldberg, Axel Grothey, Charles S. Fuchs, Kimmie Ng

Published in: Cancer Causes & Control | Issue 7/2019

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 (p_interaction = 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).

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Title: Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D3 levels and survival among patients with metastatic colorectal cancer
Authors: Chen Yuan
Lindsay Renfro
Pratibha B. Ambadwar
Fang-Shu Ou
Howard L. McLeod
Federico Innocenti
Jeffrey A. Meyerhardt
Brian M. Wolpin
Richard M. Goldberg
Axel Grothey
Charles S. Fuchs
Kimmie Ng
Publication date: 01-07-2019
Publisher: Springer International Publishing
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: Cancer Causes & Control / Issue 7/2019
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-019-01183-1

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