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Cancer Causes Control. 2019 Jul;30(7):757-765. doi: 10.1007/s10552-019-01183-1. Epub 2019 May 18.

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

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA. chen_yuan@dfci.harvard.edu.
2
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
3
Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
4
DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, FL, USA.
5
Eshelman School of Pharmacy and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
6
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
7
West Virginia University Cancer Institute, Morgantown, WV, USA.
8
Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
9
Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT, USA.

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 (pā€‰=ā€‰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 (pinteractionā€‰=ā€‰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 ).

KEYWORDS:

25-hydroxyvitamin D3; Metastatic colorectal cancer; Single-nucleotide polymorphisms; Survival

PMID:
31104167
DOI:
10.1007/s10552-019-01183-1

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