Open AccessAssociations between common polymorphisms in CYP2R1 and GC, Vitamin D intake and risk of colorectal cancer in a prospective case-cohort study in Danes
Author(s) -
Tine Iskov Kopp,
Ulla Vogel,
Vibeke Andersen
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0228635
Subject(s) - colorectal cancer , prospective cohort study , medicine , vitamin d and neurology , cohort study , case control study , oncology , cohort , physiology , cancer
Background The association between vitamin D and incidence of colorectal cancer has been thoroughly investigated, but the results are conflicting. The objectives in this study were to investigate whether two functional polymorphisms in GC and CYP2R1 , respectively, previously shown to predict vitamin D concentrations, were associated with risk of colorectal cancer; and further, to assess gene-environment interaction between the polymorphisms and intake of vitamin D through diet and supplementation in relation to risk of colorectal cancer. Methods A nested case-cohort study of 920 colorectal cancer cases and 1743 randomly selected participants from the Danish prospective “Diet, Cancer and Health” study was performed. Genotypes CYP2R1 /rs10741657 and GC /rs4588 were determined by PCR-based KASP ™ genotyping assay. Vitamin D intake from supplements and diet was assessed from a validated food frequency questionnaire. Incidence rate ratios were estimated by the Cox proportional hazards model, and interactions between polymorphisms in GC and CYP2R1 and vitamin D intake in relation to risk of colorectal cancer were assessed. Results Neither of the two polymorphisms was associated with risk of colorectal cancer per se . Heterozygote carriage of CYP2R1 /rs10741657 and GC /rs4588, and carriage of two risk alleles (estimated by a genetic risk score) were weakly associated with 9–12% decreased risk of colorectal cancer per 3 μg intake of vitamin D per day (IRR CYP2R1 /rs10741657 = 0.88, 95% CI: 0.79–0.97; IRR GC /rs4588 = 0.91, 95% CI: 0.82–1.01, IRR GRS2 = 0.90, 95% CI: 0.81–0.99). Conclusions The results suggest that genetic variation in vitamin D metabolising genes may influence the association between vitamin D intake, through food and supplementation, and risk of colorectal cancer. Clinical trial registry NCT03370432 . Registered 12 December 2017 (retrospectively registered).