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

Abstract

A protective effect of calcium and/or dairy products on colorectal cancer has been reported in epidemiological studies but the findings are considered inconsistent. In particular, it is unclear whether they act at a particular step of the adenoma-carcinoma sequence. To investigate the effect of dairy product consumption and dietary calcium, vitamin D and phosphorus intake on the adenoma-carcinoma sequence in the French E3N-EPIC prospective study. The population for the study of risk factors for adenomas was composed of 516 adenoma cases, including 175 high-risk adenomas, and of 4,804 polyp-free subjects confirmed by colonoscopy. The population for the colorectal cancer study was composed of 172 cases and 67,312 cancer-free subjects. Diet was assessed using a self-administered questionnaire completed at baseline. There was a trend of decreasing risk of both adenoma (p trend 5 0.04) and cancer (p trend 50.08) with increasing calcium intake, with RRs for adenoma and cancer of 0.80 (IC 95%50.62-1.03) and 0.72 (95% CI50.47-1.10), respectively, in the fourth quartile compared to the first. A protective effect of dairy products on adenoma (RR Q4 vs. Q1 5 0.80, 95% CI50.62-1.05, p trend 5 0.04) was observed and of milk consumption on colorectal cancer (RR Q4vs. Q1 5 0.54, 95% CI50.33-0.89, p trend 5 0.09), although the latter did not reach significance. Phosphorus intake also decreased the risk of adenoma (RR Q4 vs. Q1 50.70, 95% CI50.54-0.90, p trend 5 0.005). No vitamin D effect was identified. Our data support the hypothesis that calcium, dairy products and phosphorus exert a protective effect at certain steps of the adenoma-carcinoma sequence. ' 2005 Wiley-Liss, Inc.Key words: colorectal cancer; colorectal adenoma; calcium; vitamin D; phosphorus; dairy productThe idea that an intake of calcium and vitamin D might protect against colorectal cancer was first suggested by Newmark et al. 1 In experimental studies, low calcium diets have consistently been associated with increased cell proliferation and low cell differentiation. 2 It has therefore been suggested that calcium acts directly on epithelial cell proliferation and differentiation, as well as indirectly by forming insoluble soaps with secondary bile acids, although this point has never been formally demonstrated. 2,3 Vitamin D plays a major role in the homeostasis of calcium and 2 studies have also suggested that it reduces epithelial cell proliferation and promotes differentiation. 2,4 It has been further suggested that polymorphisms of the vitamin D receptor (VDR) might modulate this effect. 5 However, findings from epidemiological studies on the relationship between calcium or dairy product intake and risk of colorectal adenoma or/and of cancer were judged inconsistent in 2 reviews, 6,7 except for a steady protective effect of dairy product reported in cohort studies. 6 Although a meta-analysis 8 concluded that calcium had no protective effect on colorectal tumours, prospective studies and large case-control studies subsequently found a modestly beneficial ...

Calcium intake and colorectal adenoma risk: Dose‐response meta‐analysis of prospective observational studies

“…A total of 14 studies 11,[14][15][16][27][28][29][30][31][32][33][34][35][36] were eligible for the inclusion in dose-response meta-analysis of total calcium intake and adenoma risk (Supporting Information Table 2). Across the studies, types of adenomas investigated varied.…”

“…Across the studies, types of adenomas investigated varied. The study by Lieberman et al 27 specifically investigated advanced adenomas and the other 13 studies primarily examined total adenomas with some studies 11,16,27,29,34,35 further conducting subgroup analysis by adenoma subtypes. Two studies 35,36 exclusively investigated recurrent adenomas and the other 12 studies examined occurrent adenomas.…”

“…While accumulating evidence suggests that calcium may be more protective against advanced adenomas, 9,11,16,29,35 there is no sufficient a priori evidence to suspect that the effect of calcium may differ by recurrent versus occurrent adenomas. Thus, doseresponse meta-analysis of total calcium intake and adenoma risk was based on 13 studies 11,[14][15][16][28][29][30][31][32][33][34][35][36] excluding the study by Lieberman et al, 27 which was included only in the subgroup analysis for high-risk adenomas.…”

Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence

“…Furthermore, there is evidence that vitamin D and calcium may act together to reduce CRA recurrence. 22 Dairy products are an important source of calcium, and in the United States, milk is fortified with vitamin D. High dairy product intake is associated with reduced incidence of both CRA 23 and CRC, 24,25 and milk consumption, which is the main component of dairy product intake for most individuals, was concluded to result in ''probable decreased risk'' of CRC in the recent World Cancer Research Fund/American Institute for Cancer Research report into food, nutrition, physical activity and the prevention of cancer. 26 The VDR is responsible for mediating the effects of vitamin D, and functioning of the VDR has been shown to be influenced by polymorphisms in the VDR gene.…”

True and False Dangers of Milk and Milk Products

“…En tout état de cause, le principal auteur de cette observation (Walter Willett), avec de nombreux autres scientifiques et médecins, affirme dans le volumineux rapport du WCRF (18) que rien ne permet d'incriminer les produits laitiers en eux-mêmes dans cette pathologie. Sans oublier que la consommation de produits laitiers est liée à une diminution du risque de cancer colo-rectal de 15 % à 40 % selon les études (19) et probablement du cancer du sein (20). Le danger, peu documenté pour le moment, doit-il occulter les réels bénéfices ?…”