Calcium, vitamin D and colorectal cancer chemoprevention

doi:10.1016/j.bpg.2011.10.001

Best Practice & Research Clinical Gastroenterology

Volume 25, Issues 4–5, August–October 2011, Pages 485-494

https://doi.org/10.1016/j.bpg.2011.10.001 Get rights and content

Identifying modifiable risk factors, particularly dietary factors, which have been hypothesized to play an important role in colorectal carcinogenesis, remains crucial in developing primary prevention strategies. Calcium and vitamin D have been shown consistently in experimental studies to have anti-cancerous properties including but not limited to stimulating differentiation, reducing proliferation, and inducing apoptosis. The majority of epidemiologic studies consistently support an approximately 20–30% reduction in risk of colorectal cancer and adenomas comparing high to low intake categories of both calcium and vitamin D, although independent effects may not be adequately separated. Less consistency exists on the dose–response relation for both nutrients. Intake of calcium of not more than 1000 mg/d and intake of vitamin D of 1000–2000 IU/d, achieving a level of at least 30 ng/mL, appear important for colorectal cancer prevention. More study is warranted to determine the optimal intake levels and duration to reduce the colorectal cancer risk.

Introduction

Colorectal cancer is the third most common type of cancer in both men and women worldwide. Higher incidence rates are observed in high-income countries compared to middle- and low-income countries, though incidence rates are increasing rapidly in low to middle-income areas [1]. Around the world, age-adjusted incidence rates range from 30 or more per 100,000 people in North America, parts of Europe, Australia, New Zealand, and Japan to less than 5 per 100,000 in much of Africa and parts of Asia [2]. The substantial difference in incidence rates across geographic regions suggests the importance of environmental influences on colorectal carcinogenesis. Substantial research conducted in past decades has advanced our understanding of colorectal cancer aetiology. As summarized in a 2010 review, [3] some lifestyle, nutritional, and medication factors have been identified to be associated with colorectal cancer risk. With respect to dietary factors however, the effect on colorectal cancer remains largely uncertain [1], *[4]. Among these factors, calcium and vitamin D appear to show great potential for colorectal cancer prevention. This review aims to provide a brief review of a few human clinical trials and epidemiologic studies on calcium and vitamin D on sporadic colorectal adenoma and cancer risk. Although effects of these nutrients may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR), relatively limited data are available to date [5], [6], [7] and these data were not reviewed here.

Section snippets

Calcium and colorectal cancer

Calcium is an essential nutrient and plays an important role in muscular contraction, cellular growth, cell adhesion, and bone formation. The calcium-colorectal cancer hypothesis has evolved over time. In 1980, Garland and Garland proposed that vitamin D was a protective factor for colon cancer based on ecologic data showing variation of colon cancer mortality rates by latitudes [8]. One of the mechanisms to explain this potential effect of vitamin D was through enhanced calcium absorption.

Vitamin D and colorectal cancer

As an essential nutrient, in addition to an important role in bone health and maintenance of calcium balance, vitamin D exerts various physiological functions. Experimental studies showed that many cell types including colorectal cells express vitamin D receptors and 1-α-hydroxylase, and are therefore capable to convert 25-hydroxyvitamin D (25(OH)D) into 1,25(OH)₂ vitamin D, the most active metabolite of vitamin D [52]. Activation of these receptors by 1,25(OH)₂D has anti-cancerous properties

Summary

Overall, the current epidemiologic evidence supports a beneficial role of calcium and vitamin D in colorectal carcinogenesis *[4], *[56], [60]. Because of the limitations of observational studies [70], these data do not prove a cause–effect relation, but they are strongly suggestive of such an effect. Confounding seem unlikely entirely account for all these associations. In addition, these associations were supported by numerous in vitro, animal and clinical studies that indicate that calcium

Conflict of interest

None.

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4Calcium, vitamin D and colorectal cancer chemoprevention

Introduction

Section snippets

Calcium and colorectal cancer

Vitamin D and colorectal cancer

Summary

Conflict of interest

Am J Clin Nutr

Am J Clin Nutr

Am J Clin Nutr

Lancet

Clin Ther

Mutat Res

Am J Clin Nutr

J Steroid Biochem Mol Biol

J Steroid Biochem Mol Biol

Food, nutrition and the prevention of cancer: a global perspective

Wash (DC) Am Inst for Cancer Res

Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008

Int J Cancer

Primary prevention of colorectal cancer

Gastroenterology

Vitamin D receptor and calcium sensing receptor polymorphisms and the risk of colorectal cancer in European populations

Cancer Epidemiol Biomark Prev

Dietary calcium, vitamin D, VDR genotypes and colorectal cancer

Int J Cancer

Associations between BMI, energy intake, energy expenditure, VDR genotype and colon and rectal cancers (United States)

Cancer Causes Control

Do sunlight and vitamin D reduce the likelihood of colon cancer?

Int J Epidemiol

Advancing the calcium-colorectal cancer hypothesis

J Natl Cancer Inst

Colon cancer and dietary fat, phosphate, and calcium: a hypothesis

J Natl Cancer Inst

Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer

N Engl J Med

Calcium and the prevention of colon cancer

J Cell Biochem Suppl

Cellular mechanisms of calcium and vitamin D in the inhibition of colorectal carcinogenesis

Ann N Y Acad Sci

Calcium, vitamin D, and colon cancer

Cancer Res

Update of preclinical and human studies of calcium and colon cancer prevention

World J Gastroenterol

Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms

Nat Rev Cancer

Calcium does not protect against colorectal neoplasia

Epidemiology

Calcium and vitamin D intake and risk of colorectal cancer: the multiethnic cohort study

Am J Epidemiol

Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study

Int J Cancer

Dietary intake of calcium, fiber and other micronutrients in relation to colorectal cancer risk: results from the Shanghai Women’s Health Study

Int J Cancer

Calcium, vitamin D, dairy products, and risk of colorectal cancer in the cancer prevention study II nutrition cohort (United States)

Cancer Causes Control

Intake of selected micronutrients and risk of colorectal cancer

Int J Cancer

Calcium, vitamin D, sunshine exposure, dairy products and colon cancer risk (United States)

Cancer Causes Control

Diet and colon cancer in Los Angeles County, California

Cancer Causes Control

Influence of dietary levels of fat, cholesterol, and calcium on colorectal cancer

Nutr Cancer

Cereal fiber, calcium, and colorectal cancer

Cancer

Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants

Digestion

4
Calcium, vitamin D and colorectal cancer chemoprevention