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Advanced Colon Cancer risk is doubled or halved with 1000 IU of Vitamin D, depends on Vitamin D Receptors – RCT May 2017

Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas: A Randomized Clinical Trial.

JAMA Oncol. 2017 May 1;3(5):628-635. doi: 10.1001/jamaoncol.2016.5917.

VitaminDWiki

No change of risk with Calcium nor many other genes
   (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR)
2200 whites - 3 - 5 years after colonoscopy, 1,000 IU of Vitamin D
Depending on VDR type: reduced risk by 64% or increased risk by 41%
Note: I do not recall any study showing that different types of VDR can
   both increase and decrease the risk of any disease
Implication: VDR should be tested before supplementing, at least for colon cancer
     Henry Lahore, Aug 2017

See also at VitaminDWiki


Barry EL1, Peacock JL2, Rees JR1, Bostick RM3, Robertson DJ4, Bresalier RS5, Baron JA6.
1 Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
2 Division of Health and Social Care Research, King's College London, London, England.
3 Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia.
4 VA Medical Center, White River Junction, Vermont.
5 Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston.
6 Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire Department of Medicine, University of North Carolina School of Medicine, Chapel Hill.

IMPORTANCE:
Despite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial.

OBJECTIVE:
To investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence.

DESIGN, SETTING, AND PARTICIPANTS:
We examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study's treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016.

INTERVENTIONS:
Daily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither.

MAIN OUTCOMES AND MEASURES:
The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing.

RESULTS:
Among the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D' = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19-0.69; P = .002; absolute risk decreased from 14.4% to 5.1%).
Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95% CI, 0.99-2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation.

CONCLUSIONS AND RELEVANCE:
Our findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00153816.

PMID: 27978548 DOI: 10.1001/jamaoncol.2016.5917

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