Intakes of calcium and vitamin D and risk of colorectal cancer in women

In vivo and in vitro studies have suggested a protective role of calcium and vitamin D in the development of colorectal cancer. However, epidemiologic data have been inconclusive. The authors prospectively assessed intakes of calcium and vitamin D in relation to risk of colorectal cancer in a large, prospective, female cohort from the US Women's Health Study. In 1993, 39,876 women aged > or = 45 years and free of cardiovascular disease and cancer were enrolled in the study. During an average follow-up of 10 years, 223 of 36,976 women eligible for the present study developed colorectal cancer. Intakes of calcium and vitamin D from dietary sources and supplements were assessed with a baseline food frequency questionnaire. Cox proportional hazards regression was used to estimate relative risks and 95% confidence intervals. Intakes of total calcium and vitamin D were not associated with risk of colorectal cancer; multivariate relative risks comparing the highest with the lowest quintile were 1.20 (95% confidence interval: 0.79, 1.85; p for trend = 0.21) for total calcium and 1.34 (95% confidence interval: 0.84, 2.13; p for trend = 0.08) for total vitamin D. Intakes of both nutrients from specific types of sources, including diet and supplements, were also not significantly associated with colorectal cancer risk. Data provide little support for an association of calcium and vitamin D intake with colorectal cancer risk.     

The association of intakes of vitamin D and calcium with blood pressure among women

Blood pressure and its relationship to nutritional factors, particularly intakes of calcium and vitamin D, were evaluated among 86 women, aged 20-35 yr, and 222 women, aged 55-80 yr, who were not using diuretics. Observations were based on a study of bone density among women in two communities which included blood pressure determinations, a food frequency estimate of calcium intake, a 24-h dietary recall and an extensive supplement use history. There was no significant relationship between estimated current dietary calcium consumption and blood pressure in either age group. However, in younger women, there was a significant inverse relationship between estimated dietary intake of vitamin D and systolic blood pressure which remained significant (p = 0.0016) after adjusting for age, Quetelet index, alcohol consumption and calcium intake. Older women whose consumption of both vitamin D and calcium was less than the Recommended Dietary Allowance, 400 IU/day and 800 mg/day respectively, had a significantly higher systolic blood pressure (p = 0.0371) than their counterparts whose estimated intake met the RDA for at least one of the two nutrients. Vitamin D may be related to blood pressure through its regulation of calcium absorption from the gut or its interaction with parathyroid hormone in maintaining plasma calcium homeostasis.     

Meta-analysis: Serum vitamin D and colorectal adenoma risk

ObjectiveTo perform a systematic review and meta-analysis of human studies on the association between serum 25 hydroxyvitamin D (25(OH)D) and incident, sporadic colorectal adenoma (CRA) and CRA recurrence.MethodsRelevant studies among humans were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. Due to the heterogeneity across studies in categorizing serum vitamin D levels, all results were recalculated for an increase of serum 25(OH)D by 20 ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods.ResultsOverall, 10 original studies were included. Specific results for incident CRA according to serum 25(OH)D were reported in 8 studies, and for CRA recurrence in 2 studies, respectively. In meta-analyses, summary ORs (95% confidence intervals) regarding incident and recurrent CRA, and both outcomes combined were 0.82 (0.69–0.97), 0.87 (0.56–1.35), and 0.84 (0.72–0.97), respectively, for an increase of 25(OH)D by 20 ng/ml. No publication bias was found.ConclusionOur results support suggestions that serum 25(OH)D levels are inversely associated with CRA risk.     

Consumption of trans-fatty acid and its association with colorectal adenomas

trans-Fatty acid consumption is known to have detrimental effects on cardiovascular health, but little is known about its role in digestive tract neoplasia. To investigate the association between colorectal adenomas and trans-fatty acid consumption, the authors utilized data from a cross-sectional study of 622 individuals who underwent complete colonoscopy between 2001 and 2002 at the University of North Carolina Hospitals. Participants were interviewed about demographic, lifestyle, and dietary factors thought to be related to colorectal cancer. trans-Fatty acid consumption, energy adjusted by the residual method, was categorized into quartiles based on its distribution in controls. Compared with participants in the lowest quartile of consumption, those in the highest quartile had an increased prevalence of colorectal adenomas, with an adjusted prevalence odds ratio of 1.86 (95% confidence interval: 1.04, 3.33). The authors further investigated the relation between trans-fatty acid consumption and colorectal neoplasia by examining the adenoma characteristics, with the adjusted prevalence odds ratios showing little or no difference by adenoma location, size, or number. These results suggest that consumption of high amounts of trans-fatty acid may increase the risk of colorectal neoplasia, and they provide additional support to recommendations to limit trans-fatty acid consumption.     

Dietary calcium and vitamin D intake and risk of colorectal cancer: a prospective cohort study in women

Although laboratory data and a few adenoma prevention trials suggest that calcium supplementation may reduce the risk of colorectal neoplasia, the results of observational studies of calcium intake and colorectal cancer risk are contradictory. However, few studies have examined the association among women or effects in specific colon subsites. Women with colorectal cancer diagnosed through 31 December 2000 were identified by linkage to regional cancer registries. During an average 11.3 yr of follow-up of 61,463 women, we observed 572 incident cases of colorectal cancer. Using data obtained from a 67-item food frequency questionnaire and Cox proportional hazards models to estimate rate ratios and 95% confidence intervals, we found an inverse association between dietary calcium intake and colorectal cancer risk. Women with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer (rate ratio = 0.72, 95% confidence interval = 0.056-0.93, P for trend = 0.02) compared with women with the lowest intake (median 486 mg/day). Furthermore, our results suggest that the inverse association may be strongest in relation to distal cancers and among older women. The association with dairy products was less clear, suggesting that calcium intake per se is more important than specific calcium sources. Vitamin D intake was not clearly associated with risk. In sum, our data suggest that high calcium intake may lower colorectal cancer risk.     

The role of estrogen receptor, vitamin D receptor and calcium receptor genotypes in the pathogenesis of colorectal cancer

In this study, the Xbal polymorphisms of the estrogen-, the Bsml polymorphism of the vitamin D- as well as the A986S polymorphism of the calcium-sensing receptor genes were investigated in 56 patients with colorectal cancer. The expression of erbB-2, epidermal growth factor receptor, ras, p53 and their relationship to estrogen-, vitamin D- and calcium-sensing receptor genotypes were also studied. In subjects exhibiting XX genotype of the estrogen receptor gene or bb genotype of the vitamin D receptor gene, erbB-2 expression was significantly lower compared to those with xx, Xx or BB, Bb (6/56 and 11/56 vs. 31/56 and 26/56; p = 0.0043 and 0.041). The presence of the XX alleles of estrogen receptor gene significantly correlated with the overexpression of the epidermal growth factor receptor expression in tumors, whereas in xx and Xx genotypes, significantly higher expression was seen (7/56 vs. 30/56; p = 0.049). Analyzing the combinations of the two gene allelic variants, we have found XXbb genotype to be associated with a significantly lower erbB-2 expression, compared to other combinations (Xxbb, XxBb, XXBb) (2/7 vs. 7/7, 4/5, 4/5; p = 0.0011). Patients with AA calcium-sensing receptor genotype were in higher UICC stages at the time of discovery of their disease than those with AS genotype. The AA allelic variant of the calcium-sensing gene was more frequent among patients with colorectal cancer compared to controls (36/56 vs. 36/112; p = 0.0004). Our observations raise the possibility that estrogen-, and vitamin D receptor gene polymorphisms accompanied with variable oncogene expression might influence the pathogenic processes resulting in the development of colorectal cancer. The A986S polymorphism of calcium-sensing receptor might also be a prognostic marker of the disease.     

Calcium and vitamin D intake and risk of colorectal cancer: the Multiethnic Cohort Study

The associations of intakes of calcium and vitamin D with colorectal cancer risk were examined in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). In 1993-1996, 85,903 men and 105,108 women aged > or =45 years completed a quantitative food frequency questionnaire. A total of 2,110 incident cases of colorectal cancer (1,138 in men and 972 in women) were identified through December 31, 2001. Cox proportional hazards models were used to calculate multivariate-adjusted relative risks and 95% confidence intervals. Total calcium intake (from foods and supplements) was inversely associated with colorectal cancer risk in both men (highest quintile vs. lowest: relative risk (RR) = 0.70, 95% confidence interval (CI): 0.52, 0.93; p for trend = 0.006) and women (RR = 0.64, 95% CI: 0.50, 0.83; p for trend = 0.003). The inverse association was also seen for total vitamin D intake in men (RR = 0.72, 95% CI: 0.51, 1.00; p for trend = 0.03) but not in women. Intake of dairy products was inversely associated with colorectal cancer risk, especially among nonusers of supplemental calcium (men: RR = 0.77, 95% CI: 0.59, 1.01; women: RR = 0.66, 95% CI: 0.49, 0.89). The findings support the hypothesis of protective roles for calcium, vitamin D, and dairy products in the risk of colorectal cancer.     

The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.     

Association between plasma 25-hydroxyvitamin D and colorectal adenoma according to dietary calcium intake and vitamin D receptor polymorphism

The anticarcinogenic potential of vitamin D might be mediated by not only calcium metabolism but also other mechanisms initiated by vitamin D receptor (VDR). The authors measured plasma 25-hydroxyvitamin D in healthy volunteer examinees who underwent total colonoscopy in Tokyo, Japan, 2004-2005, and evaluated its influence on colorectal adenoma, both alone and in interaction with VDR polymorphisms, which correspond to the FokI and TaqI restriction sites. The main analysis of plasma 25-hydroxyvitamin D included 737 cases and 703 controls. Compared with the lowest quintile of plasma 25-hydroxyvitamin D, only the highest was related to a significantly decreased odds ratio of colorectal adenoma (odds ratio = 0.64, 95% confidence interval: 0.45, 0.92). In contrast, all but the lowest quintile of dietary calcium intake presented similarly reduced odds ratios (odds ratio for the highest = 0.67, 95% confidence interval: 0.47, 0.95). Of note, the association between plasma 25-hydroxyvitamin D levels and colorectal adenoma was modified by the TaqI polymorphism of the VDR gene (P(interaction) = 0.03) but not by dietary calcium intake (P(interaction) = 0.93). These observations highlight the importance of vitamin D in colorectal tumorigenesis. Vitamin D might protect against colorectal neoplasia, mainly through mechanisms other than the indirect mechanism via calcium metabolism.     

Circulating 25-hydroxyvitamin-D and risk of colorectal adenomas and hyperplastic polyps

Colorectal adenomas are clear precursors of cancer; hyperplastic polyps may also have malignant potential. An inverse association between circulating vitamin D metabolites and adenoma risk has been reported, but less is known about vitamin D and hyperplastic polyps. We conducted a case-control study of adenomas and hyperplastic polyps among 459 members of an integrated health plan evaluated via colonoscopy. Questionnaires provided information on colorectal polyp risk factors, and plasma samples were assayed for 25-hydroxyvitamin-D [25(OH)D]. Polytomous regression was used to estimate odds ratios for adenomas (n = 149) and hyperplastic polyps (n = 85) compared to polyp-free controls (n = 225) by tertile of 25(OH)D. An inverse association between 25(OH)D and adenomas was suggested after adjustment for potential confounding factors [comparing upper to lower tertiles, OR (95%CI): 0.71 (0.38-1.30)]. After restriction of the analyses to study participants with no history of polyps, this OR estimate was reduced further [adjusted OR (95%CI): 0.52 (0.23-1.20)]. In comparison, no inverse association between hyperplastic polyps and 25(OH)D was observed among the full study participants [adjusted OR (95%CI): 1.17 (0.55-2.51)] or among those without prior polyps [adjusted OR (95%CI): 1.42 (0.55-3.65)]. Our study suggests that the established inverse association between circulating 25(OH)D and adenoma may not apply to hyperplastic polyps.     

Supplementation with vitamin D and calcium in long-term care residents

Vitamin D deficiency is a common finding in institutionalized older persons. Vitamin D-deficient elderly persons are at higher risk of falls and fractures. Long-term care residents should be considered at high risk of vitamin D deficiency and therefore vitamin D supplementation is highly recommended in this population. The minimal effective dose is 800 IU per day. It is recommended that vitamin D supplementation should be implemented in all patients in residential aged care facilities. In addition to vitamin D, calcium supplementation has shown to enhance the effect of vitamin D on bone. Calcium intake should be optimized (1200-1500 mg per day recommended) and supplementation offered to those with inadequate intake. The addition of calcium depends on tolerance, history of kidney stones, and emerging data regarding its cardiovascular safety.     

维生素D受体基因TAQI多态性及其缺乏性佝偻病易感因素研究

【目的】　通过研究维生素D受体 (vitaminDreceptor ,VDR)基因多态性与维生素D缺乏性佝偻病易感性的相关性 ,探讨维生素D缺乏性佝偻病的遗传易感因素。　【方法】　利用限制性内切酶TaqⅠ ,应用聚合酶链反应 限制性片断长度多态性分析及基因测序等技术测定 3 4例维生素D缺乏性佝偻病患儿和 5 2例正常儿童的VDR基因多态性 ,比较两组VDR基因型和等位基因的分布频率。　【结果】　在佝偻病患儿中TT、Tt、tt基因型分布频率分别为 88.2 %、11.8%、0 % ,T、t等位基因的分布频率分别为 94.1%、5 .9%。而正常对照组TT、Tt、tt基因分布频率分别为 90 .4%、9.6%、0 % ,T、t等位基因的分布频率为 95 .2 %、4.8%。佝偻病组和正常对照组TT、Tt、tt三种基因型分布频率差异无显著性 (χ2 =0 .0 0 9,P >0 .0 5 ) ,两组T和t等位基因的分布频率差异亦无显著性 (χ2 =0 .12 3 ,P >0 .0 5 )。　【结论】　VDR基因TaqⅠ酶切位点多态性与维生素D缺乏性佝偻病发病无关联。     

Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women

The authors examined intakes of calcium and vitamin D, and interaction with retinol, in relation to risk of adenoma of the distal colon or rectum among 48,115 US women who were free of colorectal cancer or polyps, completed a food frequency questionnaire in 1980, and underwent endoscopy by 2002. They documented 2,747 cases of adenoma (1,064 large, 1,531 small, 2,085 distal colon, and 779 rectal). Total calcium intake was weakly associated with distal colorectal adenoma risk (multivariable relative risk (RR) for extreme quintiles = 0.88, 95% confidence interval (CI): 0.74, 1.04; p(trend) = 0.06), particularly for large adenoma (RR = 0.73, 95% CI: 0.56, 0.96; p(trend) = 0.02). Total vitamin D intake was weakly associated with reduced risk of distal colorectal adenoma (RR = 0.79, 95% CI: 0.63, 0.99; p(trend) = 0.07), but more strongly with distal colon adenoma risk (RR = 0.67, 95% CI: 0.52, 0.87; p(trend) = 0.004). The combinations of high vitamin D and low retinol intake (RR = 0.55, 95% CI: 0.28, 1.10) further decreased risk of distal colorectal adenoma when compared with the opposite extreme. Higher total calcium and vitamin D intakes were associated with reduced risk, and the actions of vitamin D may be attenuated by high retinol intake.     

Changes in diet during adult life and risk of colorectal adenomas

To evaluate the associations of changes in diet during adult life with adenoma risk, data from a case-control study of 146 colorectal adenomas and 226 controls were analyzed. Dietary habits during the year before sigmoidoscopy and when subjects were 30 yr old were collected using a food-frequency questionnaire. Change in frequency of consumption during adulthood was calculated by subtracting frequency of consumption of specific foods or food groups at age 30 yr from frequency of consumption during the previous year (recent consumption). Associations with changes in frequency of consumption were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). There was no association for foods or food groups consumed at age 30 yr. For recent consumption, more frequent consumption of red meat, breakfast sausage, and pork chops/ham steaks and less frequent consumption of fish, chicken/turkey, and vegetables were related to a higher risk. Compared with individuals with the highest reduction in consumption since age 30 yr, risks were higher for those with smallest reduction in red meat intake (OR = 2.8; CI = 1.1-7.3), particularly for hamburgers/cheeseburgers (OR = 2.8; CI = 1.2-6.8) and pork chops/ham steaks (OR = 3.7; CI = 1.6-8.7). In contrast, individuals in the highest quartile of increased consumption of fish (OR = 0.6; CI = 0.3-1.1) and vegetables (OR = 0.5; CI = 0.3-1.1) had a lower risk compared with those with minimal increase in consumption. In conclusion, irrespective of frequency of consumption at age 30 yr, a greater reduction in consumption of red meat and a larger increase in consumption of vegetables since age 30 yr were associated with a decreased risk of colorectal adenomas later in life.