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Vitamin D Deficiency or Diabetes: Independent Risk Factors for Colorectal Cancer?
An individual’s risk of developing colorectal cancer (CRC) increases with advancing age. Other known risks include family history, personal history of adenomatous polyps or CRC, ethnic background, obesity, lifestyle choices such as smoking, and a diet high in red meat and/or a high-fat diet, (American Cancer Society, 2011). Other risk factors continue to be investigated. Two recent systematic review articles addressed two additional possible CRC risk factors: low vitamin D levels (Ma et al, 2011), and diabetes mellitus (Yuhara et al, 2011).

Vitamin D and Risk of CRC

Ma and colleagues (2011) conducted a meta-analysis systematic review of prospective studies assessing the association of vitamin D intake or blood levels of 25-hydroxyvitamin D [25(OH)D] with the risk of CRC. Relevant studies were identified by a search of MEDLINE and EMBASE databases before October 2010 with no restrictions. These prospective studies reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between vitamin D intake or blood 25(OH)D levels and the risk of colorectal, colon, or rectal cancer; approximately 1 million participants from several countries participated in the studies identified by the researchers.

Nine studies on vitamin D intake and nine studies on blood 25(OH)D levels were included in the meta-analysis. The pooled RRs of CRC for the highest versus lowest categories of vitamin D intake and blood 25(OH)D levels were 0.88 (95% CI, 0.80 to 0.96) and 0.67 (95% CI, 0.54 to 0.80), respectively. There was no heterogeneity among studies of vitamin D intake (P = .19) or among studies of blood 25(OH)D levels (P = .96). A 10 ng/mL increment in blood 25(OH)D level conferred an RR of 0.74 (95% CI, 0.63 to 0.89).

The authors concluded that vitamin D intake and blood 25(OH)D levels were inversely associated with the risk of colorectal cancer in this meta-analysis.

Diabetes Mellitus and Risk of CRC

Although the American Cancer Society (2011) and some patient information webpages identify diabetes mellitus (DM) as a risk factor for CRC, the subject continues to be debated in the medical literature. Yuhara et al (2011) conducted a meta-analysis of case control and cohort studies to evaluate whether the association between diabetes and CRC varied by sex, and assessed potential confounding factors including obesity, smoking, and exercise. The researchers identified studies by searching the EMBASE and MEDLINE databases (from inception through 31 December 2009) and by searching bibliographies of relevant articles. Summary RRs with 95% CIs were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias.

Diabetes was associated with an increased risk of colon cancer (summary RR 1.38, 95% CI 1.26 – 1.51; n = 14 studies) and RC (summary RR 1.20, 95% CI 1.09 – 1.31; n = 12 studies). The association remained when the meta-analysis was limited to studies that either controlled for smoking and obesity, or for smoking, obesity,and physical exercise. Diabetes was associated with an increased risk of colon cancer for both men (summary RR 1.43, 95% CI 1.30 – 1.57; n = 11 studies) and women (summary RR 1.35, 95% CI 1.14 – 1.53; n = 10 studies). For rectal cancer, there was a significant association between DM and cancer risk for men (summary RR 1.22, 95% CI 1.07 – 1.40; n = 8 studies), but not for women (summary RR 1.09, 95% CI = 0.99 – 1.19; n = 8 studies).

The authors concluded that the data suggest that DM is an independent risk factor for colon and rectal cancer. Although these findings are based on observational epidemiological studies that have inherent limitations due to diagnostic bias and confounding, subgroup analyses confirmed the consistency of the findings across study type and population.

ManageCRC.com Commentary

There are multiple proven risk factors for development of CRC and many of those risk factors also contribute to the development of diabetes: obesity, lack of exercise and poor diet among them. All of these are confounding factors when trying to tease out the actual risk factor; however, the study noted in this article took those risk factors into account as variables across studies. If type 2 diabetes is increasing in the world population, the incidence of CRC should also increase if, in fact, diabetes is found to increase the risk of CRC. Vitamin D deficiency is more common than previously thought, and reportedly also is on the rise, especially in areas or in populations where the liberal use of sunscreen is recommended to prevent skin cancer (Holick et al, 2011). As noted in a recent editorial on the vitamin D/cancer controversy, Viale (2011) commented on the need for further research into vitamin D and the link to cancer: “Although a definite link between vitamin D and the prevention of cancer has not yet been made, ongoing studies continue to research this intriguing potential therapy. For now, communication with patients should reveal the level of evidence currently available, and the need for further research on the role of vitamin D in the cancer population” (Viale, 2011, p. 291).

Although both of these risk factors require further study in prospective, randomized clinical trials, these reviews provide information that can assist in development of more accurate risk models and CRC screening guidelines.


American Cancer Society. (2011). Colorectal Cancer. Retrieved from http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-risk-factors

Holick, M.F., Binkley N.C., Bischoff-Ferrari, H.A., Gordon, C.M., Hanley, D.A., Heaney, R.P.,…Weaver, C.M. (2011). Evaluation, treatment, and prevention of vitamin d deficiency: An endocrine society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. Published online before print 6 June 2011. doi:10.1210/jc.2011-0385  Link to abstract http://jcem.endojournals.org/content/early/2011/06/03/jc.2011-0385

Ma, Y., Zhang, P., Wang, F., Yang, J, Lin, Z., & Qin, H. (2011). Association between vitamin D and risk of colorectal cancer: A systematic review of prospective studies. Journal of Clinical Oncology, 29, 3775-3782. doi:10.1200/JCO.2011.35.7566   Link to abstract http://jco.ascopubs.org/content/early/2011/08/28/JCO.2011.35.7566.abstract?cited-by=yes&legid=jco;JCO.2011.35.7566v1

Viale, P.H. (2011). Prevention of cancer? The vitamin D controversy. [Editorial]. Journal of the Advanced Practitioner in Oncology (JADPRO), 2, 290-291. Link to article http://www.advancedpractitioner.com/journal/toc.html Free registration required for full text.

Yuhara, H., Steinmaus, C., Cohen, S.E., Corley, D.A., Tei, Y., & Buffler, P.A. (2011). Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer? American Journal of Gastroentrology. Advance online publication 13 September 2011. doi:10.1038/ajg.2011.301  Link to abstract http://www.nature.com/ajg/journal/vaop/ncurrent/full/ajg2011301a.html

Article Created On : 10/10/2011 11:04:19 AM             Article Updated On : 10/10/2011 11:04:19 AM