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Nutrients 2018, 10(1), 55; doi:10.3390/nu10010055

Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women

1
Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
2
Harvard Medical School, Boston, MA 02115, USA
3
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
5
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
6
Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA 02115, USA
7
Mary Horrigan Connors Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Received: 29 September 2017 / Revised: 30 November 2017 / Accepted: 13 December 2017 / Published: 9 January 2018
(This article belongs to the Special Issue Dietary Supplements)
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Abstract

Some observational studies suggest an inverse association between circulating 25-hydroxyvitamin D (25OHD) and cancer incidence and mortality. We conducted a Mendelian randomization analysis of the relationship between a vitamin D genetic risk score (GRS, range 0–10), comprised of five single nucleotide polymorphisms (SNPs) of vitamin D status in the DHCR7, CYP2R1 and GC genes and cancer risk among women. Analysis was performed in the Women’s Genome Health Study (WGHS), including 23,294 women of European ancestry who were cancer-free at baseline and followed for 20 years for incident cancer. In a subgroup of 1782 WGHS participants with 25OHD measures at baseline, the GRS was associated with circulating 25OHD mean (SD) = 67.8 (26.1) nmol/L, 56.9 (18.7) nmol/L in the lowest versus 73.2 (27.9) nmol/L in the highest quintile of the GRS (p trend < 0.0001 across quintiles). However, in age-adjusted Cox proportional hazards models, higher GRS (reflecting higher 25OHD levels) was not associated (cases; Hazard Ratio (HR) (95% Confidence Interval (CI)), p-value) with incident total cancer: (n = 3985; 1.01 (1.00–1.03), p = 0.17), breast (n = 1560; 1.02 (0.99–1.05), p = 0.21), colorectal (n = 329; 1.06 (1.00–1.13), p = 0.07), lung (n = 330; 1.00 (0.94–1.06), p = 0.89) or total cancer death (n = 770; 1.00 (0.96–1.04), p = 0.90). Results were similar in fully-adjusted models. A GRS for higher circulating 25OHD was not associated with cancer incidence or mortality. View Full-Text
Keywords: vitamin D; cancer; genetic risk score; Mendelian randomization; mortality vitamin D; cancer; genetic risk score; Mendelian randomization; mortality
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Chandler, P.D.; Tobias, D.K.; Wang, L.; Smith-Warner, S.A.; Chasman, D.I.; Rose, L.; Giovannucci, E.L.; Buring, J.E.; Ridker, P.M.; Cook, N.R.; Manson, J.E.; Sesso, H.D. Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women. Nutrients 2018, 10, 55.

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