Circulating Vitamin D and colorectal cancer risk: An international pooling project of 17 cohorts

McCullough, Marjorie L.; Zoltick, Emilie S.; Weinstein, Stephanie J.; Fedirko, Veronika; Wang, Molin; Cook, Nancy R.; Eliassen, A. Heather; Zeleniuch-Jacquotte, Anne; Agnoli, Claudia; Albanes, Demetrius; Barnett, Matthew J.; Buring, Julie E.; Campbell, Peter T.; Clendenen, Tess V.; Freedman, Neal D.; Gapstur, Susan M.; Giovannucci, Edward L.; Goodman, Gary G.; Haiman, Christopher A.; Ho, Gloria Y. F.; Horst, Ronald L.; Hou, Tao; Huang, Wen-Yi; Jenab, Mazda; Jones, Michael E.; Joshu, Corinne E.; Krogh, Vittorio; Lee, I-Min; Lee, Jung Eun; Mannisto, Satu; Le Marchand, Loic; Mondul, Alison M.; Neuhouser, Marian L.; Platz, Elizabeth A.; Purdue, Mark P.; Riboli, Elio; Robsahm, Trude Eid; Rohan, Thomas E.; Sasazuki, Shizuka; Schoemaker, Minouk J.; Sieri, Sabina; Stampfer, Meir J.; Swerdlow, Anthony J.; Thomson, Cynthia A.; Tretli, Steinar; Tsugane, Schoichiro; Ursin, Giske; Visvanathan, Kala; White, Kami K.; Wu, Kana; Yaun, Shiaw-Shyuan; Zhang, Xuehong; Willett, Walter C.; Gail, Mitchel H.; Ziegler, Regina G.; Smith-Warner, Stephanie A.

doi:10.1093/jnci/djy087

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Circulating Vitamin D and colorectal cancer risk: An international pooling project of 17 cohorts

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Authors: McCullough, Marjorie L.; Zoltick, Emilie S.; Weinstein, Stephanie J.; Fedirko, Veronika; Wang, Molin; Cook, Nancy R.; Eliassen, A. Heather; Zeleniuch-Jacquotte, Anne; Agnoli, Claudia; Albanes, Demetrius; Barnett, Matthew J.; Buring, Julie E.; Campbell, Peter T.; Clendenen, Tess V.; Freedman, Neal D.; Gapstur, Susan M.; Giovannucci, Edward L.; Goodman, Gary G.; Haiman, Christopher A.; Ho, Gloria Y. F.; Horst, Ronald L.; Hou, Tao; Huang, Wen-Yi; Jenab, Mazda; Jones, Michael E.; Joshu, Corinne E.; Krogh, Vittorio; Lee, I-Min; Lee, Jung Eun; Mannisto, Satu; Le Marchand, Loic; Mondul, Alison M.; Neuhouser, Marian L.; Platz, Elizabeth A.; Purdue, Mark P.; Riboli, Elio; Robsahm, Trude Eid; Rohan, Thomas E.; Sasazuki, Shizuka; Schoemaker, Minouk J.; Sieri, Sabina; Stampfer, Meir J.; Swerdlow, Anthony J.; Thomson, Cynthia A.; Tretli, Steinar; Tsugane, Schoichiro; Ursin, Giske; Visvanathan, Kala; White, Kami K.; Wu, Kana; Yaun, Shiaw-Shyuan; Zhang, Xuehong; Willett, Walter C.; Gail, Mitchel H.; Ziegler, Regina G.; Smith-Warner, Stephanie A.

Issue Date: 2019-02

Publisher: Oxford University Press

Citation: Journal of the National Cancer Institute, Vol.111 No.2, pp.158-169

Abstract: Background Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. Results Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided P-heterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. Conclusions Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.