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Nutrients. 2018 Jan 9;10(1). pii: E55. doi: 10.3390/nu10010055.

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

Chandler PD1,2, Tobias DK3,4, Wang L5,6, Smith-Warner SA7,8,9, Chasman DI10,11, Rose L12, Giovannucci EL13,14,15,16, Buring JE17,18, Ridker PM19,20,21, Cook NR22,23, Manson JE24,25,26,27,28, Sesso HD29,30,31.

Author information

1
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. pchandler@partners.org.
2
Harvard Medical School, Boston, MA 02115, USA. pchandler@partners.org.
3
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. dtobias@partners.org.
4
Harvard Medical School, Boston, MA 02115, USA. dtobias@partners.org.
5
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. lwang284@its.jnj.com.
6
Harvard Medical School, Boston, MA 02115, USA. lwang284@its.jnj.com.
7
Harvard Medical School, Boston, MA 02115, USA. swarner@hsph.harvard.edu.
8
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. swarner@hsph.harvard.edu.
9
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. swarner@hsph.harvard.edu.
10
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Dchasman@partners.org.
11
Harvard Medical School, Boston, MA 02115, USA. Dchasman@partners.org.
12
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. lrose@rics.bwh.harvard.edu.
13
Harvard Medical School, Boston, MA 02115, USA. egiovann@hsph.harvard.edu.
14
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. egiovann@hsph.harvard.edu.
15
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. egiovann@hsph.harvard.edu.
16
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. egiovann@hsph.harvard.edu.
17
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. jburing@partners.org.
18
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. jburing@partners.org.
19
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. pridker@partners.org.
20
Harvard Medical School, Boston, MA 02115, USA. pridker@partners.org.
21
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. pridker@partners.org.
22
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. ncook@partners.org.
23
Harvard Medical School, Boston, MA 02115, USA. ncook@partners.org.
24
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. jmanson@partners.org.
25
Harvard Medical School, Boston, MA 02115, USA. jmanson@partners.org.
26
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. jmanson@partners.org.
27
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. jmanson@partners.org.
28
Mary Horrigan Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, MA 02115, USA. jmanson@partners.org.
29
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. hsesso@partners.org.
30
Harvard Medical School, Boston, MA 02115, USA. hsesso@partners.org.
31
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. hsesso@partners.org.

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.

KEYWORDS:

Mendelian randomization; cancer; genetic risk score; mortality; vitamin D

PMID:
29315215
PMCID:
PMC5793283
DOI:
10.3390/nu10010055
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Paul M. Ridker received research support from AstraZeneca, Novartis, Roche and Sanofi-Aventis. No other authors declare any conflict of interest.

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