Calcium Plus Vitamin D Supplementation and the Risk of Colorectal Cancer

Department of Social and Preventive Medicine, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, USA.
New England Journal of Medicine (Impact Factor: 55.87). 03/2006; 354(7):684-96. DOI: 10.1056/NEJMoa055222
Source: PubMed


Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.
We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.
The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.
Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. ( number, NCT00000611.).

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Available from: Tamsen Lynn Bassford
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    • "Cigarette smoking has been associated with increased incidence and mortality from CRC [9]. Physical activity, diet high in fruits and vegetables , fiber, resistant starch, folic acid and folate, vitamin B6 (pyridoxine), calcium and dairy products , vitamin D, magnesium, garlic, fish consumption and drugs (aspirin and NSAIDs) are protective factors against CRC [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]. "
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    ABSTRACT: Abstract: Background: The aim of this study was to evaluate paraoxonase-1 (PON1) and arylesterase (ARE) activities and oxidative stress status in patients with colorectal carcinomas (CRC). Materials and methods: Thirty-three patients (20 male, 13 female) with CRC and 30 healthy controls were enrolled in the study. Blood samples were obtained from the CRC patients before adjuvant therapy. Serum samples from CRC patients and healthy controls were analyzed for PON1 and ARE activities. Results: The PON1 and ARE activities of the patients with CRC were significantly higher compared to those of the control group (PON1 activity is 125.35±20.07 U/L for CRC patients and 1.22±0.48 U/L for control group, P<0.001; ARE activity is 160.76±10.79 U/L for CRC patients). ARE levels showed a positive correlation with smoking status (P=0.04). PON1 activity was higher in colon carcinoma patients (135.95±19.3 U/L) rather than rectal carcinoma patients (97.08±5.24 U/L) but it was not statistically significant (P=0.72). Conclusion: Serum PON1 activity is increased in patients with CRC, and serum ARE levels showed a positive correlation with smoking status. PON1 activity was higher in colon carcinoma patients. There is no other study in literature investigating these activities for CRC patients. It should be reevaluated by larger clinical trials.
    Full-text · Article · Jan 2015
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    • "A meta-analysis of 35 independent case-control and cohort studies investigating the association of serum 25(OH)D levels with cancer showed a consistent inverse relationship between circulating 25(OH)D levels and colorectal cancer risk [11]; no similar conclusions could however be drawn for other cancer sites. Notably, so far none of the randomised, controlled trials has shown that vitamin D supplementation can prevent cancer [12] [13] although the increase in vitamin D serum levels achieved in one of these trials, the Women's Health Initiative study, was probably insufficient [14]. "
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    ABSTRACT: Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.
    Full-text · Article · Jul 2014 · European journal of cancer (Oxford, England: 1990)
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    • "A preliminary analysis of the WHI RCT does not reveal that calcium supplements cut the risk of CRC after a seven-year follow-up.27 Yet a re-evaluation of these data consistently shows an interaction with estrogens, to the extent that calcium modifies the effect on the relation with a risk of CRC depending on whether estrogens are administered concomitantly or not.47 "
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    ABSTRACT: Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. Modifiable risk factors of CRC include smoking, physical inactivity, being overweight and obesity, eating processed meat, and drinking alcohol excessively. CRC screening programs are possible only in economically developed countries. However, attention should be paid in the future to geographical areas with ageing populations and a western lifestyle.19,20 Sigmoidoscopy screening done with people aged 55-64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%.
    Full-text · Article · Jul 2014 · Clinical Medicine Insights: Gastroenterology
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