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Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms : A Pooled, Nested, Case-Control Study

Gibbs, David Corley (författare)
Song, Mingyang (författare)
McCullough, Marjorie L. (författare)
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Um, Caroline Y. (författare)
Bostick, Roberd M. (författare)
Wu, Kana (författare)
Flanders, W. Dana (författare)
Giovannucci, Edward (författare)
Jenab, Mazda (författare)
Brustad, Magritt (författare)
Tjonneland, Anne (författare)
Perez-Cornago, Aurora (författare)
Trichopoulou, Antonia (författare)
Tsilidis, Konstantinos K. (författare)
Hultdin, Johan (författare)
Umeå universitet,Patologi
Gurrea, Aurelio Barricarte (författare)
Bueno-de-Mesquita, Bas (författare)
Mahamat-Saleh, Yahya (författare)
Kuehn, Tilman (författare)
Gunter, Marc J. (författare)
Weiderpass, Elisabete (författare)
Fedirko, Veronika (författare)
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Oxford University Press, 2020
Ingår i: JNCI CANCER SPECTRUM. - : Oxford University Press. - 2515-5091. ; 4:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability. Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, seasonstandardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided. Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, P-trend = 1.2 x 10(-8)). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (> 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (P-heterogeneity = .01). Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.


MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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