Role of Supplemental Calcium in the Recurrence of Colorectal Adenomas: A Metaanalysis of Randomized Controlled Trials

Shaukat, Aasma; Scouras, Nicole; Schünemann, Holger J.

doi:10.1111/j.1572-0241.2005.41220.x

Cited by 97 publications

(69 citation statements)

References 24 publications

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“…The estimated "weighted mean RRs" for calcium and aspirin were 0.79 and 0.85 respectively (weighted by study size). A recently published meta-analysis finds an RR= 0.80 (CI: 0.68, 0.93) for calcium supplement (33), which is close to the value estimated here, 0.79. Interventions with high wheat bran and/or low fat diet, beta-carotene or vitamin C and E had no effect at all on polyp recurrence (34)(35)(36)(37)(38)(39).…”

Section: Experimental Chemoprevention Of Intestinal Tumours In Humanssupporting

confidence: 88%

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

Corpet

Pierre

2005

European Journal of Cancer

201

129

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To cite this version:Denis E Corpet, Fabrice Pierre. How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men.. European Journal of Cancer, Elsevier, 2005, 41 (13), pp.1911-22. <10.1016/j.ejca.2005.06.006>. D.E. Corpet, F. Pierre / European Journal of Cancer 41 (2005) 1911-1922 AbstractTumours in rodent and human colon share many histological and genetic features. To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we made a meta-analysis of aspirin, betacarotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention.

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Section: Experimental Chemoprevention Of Intestinal Tumours In Humanssupporting

confidence: 88%

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

Corpet

Pierre

2005

European Journal of Cancer

201

129

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“…64 Aspirin and calcium are currently the only agents that have shown consistent chemopreventive activity against colorectal neoplasia in randomized trials; however, not all individuals benefit from these interventions and some experience side effects. 58,65,66 On the basis of the inverse relationship observed in our study and similar associations reported in epidemiological studies, we believe that dairy products, and more specifically milk, may have value as chemopreventive agents, making a randomized trial for CRA recurrence prevention an attractive proposition.…”

Section: Discussionmentioning

confidence: 51%

“…57 Randomized trials of calcium supplementation indicate a modest but significant protective effect against CRA recurrence (pooled RR from 3 trials combined 0.80, 95%CI: 0.68-0.93). 58 In our study, calcium intake did not influence CRA recurrence, and there was no evidence of an interaction between calcium and vitamin D intake, and no influence of calcium was observed when only individuals in the high tertile of vitamin D intake were con- sidered. Daily doses of between 1,200 and 2,000 mg of calcium supplements were used in the randomized trials, however, and it is possible that the differences in calcium intakes between individuals in the low and high tertiles of intake in our study (mean difference 900 mg) were insufficient to impact on recurrence.…”

Section: Discussionmentioning

confidence: 74%

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

Muir

Liu

Logan

et al. 2008

Intl Journal of Cancer

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Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, FokI, BsmI, ApaI and TaqI polymorphisms were genotyped in 546 participants with available DNA, and gene-diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) 5 0.64; 95% confidence intervals (CIs): 0.47-0.88, for subjects in the highest compared to lowest intake tertile, p trend 5 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR 5 0.52; 95% CI: 0.38-0.72, p trend 5 3.2 3 10 25 ), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with ApaI aA/AA genotype (p interaction 5 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence. ' 2008 Wiley-Liss, Inc.Key words: colorectal adenoma recurrence; dairy products; VDR; polymorphism Colorectal cancer (CRC) is the third commonest cancer worldwide after lung and breast cancer, and two-thirds of CRC occurs in developed countries. 1 Up to 90% of CRCs develop from colorectal adenomas (CRAs) and colonoscopic removal of CRA reduces the incidence of CRC. 2,3 In some individuals, the recurrence rate for CRA is as high as 40-50% after 3 years, 4 CRA recurrence is a surrogate marker for CRC risk and prevention of CRA recurrence is a useful endpoint for evaluating chemopreventive agents. 5 Activation of vitamin D receptors (VDRs) present in many cell types, including colorectal epithelial cells, can inhibit proliferation, angiogenesis and invasiveness, and studies in animal models indicate that vitamin D supplementation can lower the incidence and metastatic potential of intestinal tumors. 6-9 Ecological studies correlating sunlight exposure with cancer incidence provided the first evidence that vitamin D levels are inversely related to CRC development in humans. 10 Subsequent epidemiological studies have reported lower risks of CRA and CRC in individuals with high intakes and circulating levels of vitamin D. 11-14 Vitamin D plays a crucial role in calcium me...

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“…Recent pooled analysis and epidemiological studies have demonstrated an inverse relationship between Ca 2þ intake and colorectal cancer or adenoma risk (111,112) . Furthermore, randomised clinical trials have shown that Ca 2þ supplementation reduces adenoma risk (113,114) . Induction of colonic hyperproliferation and expansion of an epithelial cell population containing atypical nuclei have been found in experimental animals such as rats and mice fed Western-style diets (high fat, low Ca 2þ , low vitamin D, low fibre) (115) .…”

Section: Relationship Between Dietary Ca 21 and Lipid Metabolismmentioning

confidence: 99%

Molecular mechanisms triggered by low-calcium diets

et al. 2009

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Ca is not only essential for bone mineralisation, but also for regulation of extracellular and intracellular processes. When the Ca2+ intake is low, the efficiency of intestinal Ca2+ absorption and renal Ca2+ reabsorption is increased. This adaptive mechanism involves calcitriol enhancement via parathyroid hormone stimulation. Bone is also highly affected. Low Ca2+ intake is considered a risk factor for osteoporosis. Patients with renal lithiasis may be at higher risk of recurrence of stone formation when they have low Ca2+ intake. The role of dietary Ca2+ on the regulation of lipid metabolism and lipogenic genes in adipocytes might explain an inverse relationship between dairy intake and BMI. Dietary Ca2+ restriction produces impairment of the adipocyte apoptosis and dysregulation of glucocorticosteroid metabolism in the adipose tissue. An inverse relationship between hypertension and a low-Ca2+ diet has been described. Ca2+ facilitates weight loss and stimulates insulin sensitivity, which contributes to the decrease in the blood pressure. There is also evidence that dietary Ca2+ is associated with colorectal cancer. Dietary Ca2+ could alter the ratio of faecal bile acids, reducing the cytotoxicity of faecal water, or it could activate Ca2+-sensing receptors, triggering intracellular signalling pathways. Also it could bind luminal antigens, transporting them into mucosal mononuclear cells as a mechanism of immunosurveillance and promotion of tolerance. Data relative to nutritional Ca2+ and incidences of other human cancers are controversial. Health professionals should be aware of these nutritional complications and reinforce the dairy intakes to ensure the recommended Ca2+ requirements and prevent diseases.

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Role of Supplemental Calcium in the Recurrence of Colorectal Adenomas: A Metaanalysis of Randomized Controlled Trials

Abstract: This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Cited by 97 publications

References 24 publications

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men

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

Molecular mechanisms triggered by low-calcium diets

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