Vitamin D Receptor and Calcium Sensing Receptor Polymorphisms and the Risk of Colorectal Cancer in European Populations

Lifestyle and Cancer Group, IARC, 150 Cours Albert Thomas, 69008, Lyon, France.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 09/2009; 18(9):2485-91. DOI: 10.1158/1055-9965.EPI-09-0319
Source: PubMed


Increased levels of vitamin D and calcium may play a protective role in colorectal cancer (CRC) risk. It has been suggested that these effects may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). However, current epidemiologic evidence from European populations for a role of these genes in CRC risk is scarce. In addition, it is not clear whether these genes may modulate CRC risk independently or by interaction with blood vitamin D concentration and level of dietary calcium intake. A case-control study was conducted nested within the European Prospective Investigation into Cancer and Nutrition. CRC cases (1,248) were identified and matched to 1,248 control subjects. Genotyping for the VDR (BsmI: rs1544410; Fok1: rs2228570) and CASR (rs1801725) genes was done by Taqman, and serum vitamin D (25OHD) concentrations were measured. Conditional logistic regression was used to estimate the incidence rate ratio (RR). Compared with the wild-type bb, the BB genotype of the VDR BsmI polymorphism was associated with a reduced risk of CRC [RR, 0.76; 95% confidence interval (CI), 0.59-0.98). The association was observed for colon cancer (RR, 0.69; 95% CI, 0.45-0.95) but not rectal cancer (RR, 0.97; 95% CI, 0.62-1.49). The Fok1 and CASR genotypes were not associated with CRC risk in this study. No interactions were noted for any of the polymorphisms with serum 25OHD concentration or level of dietary calcium. These results confirm a role for the BsmI polymorphism of the VDR gene in CRC risk, independent of serum 25OHD concentration and dietary calcium intake.

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    • "Contrary, SS or BB genotype individuals consuming high level of calcium had reduced risk of colon cancer [56]. The protective effect of high dietary calcium intake for these with BB genotype of the VDR BsmI has been also observed in some other investigations [57]. There was also a study on interactions between polymorphism of adenomatous polyposis coli gene (APC), dietary calcium and fiber intake and CRC showing that the group of high both calcium and fiber intakes was associated with about 50% lower risk of CRC among individuals with DV or VV genotype of APC [58]. "
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    ABSTRACT: An unfavorable trend of increasing rates of colorectal cancer has been observed across modern societies. In general, dietary factors are understood to be responsible for up to 70% of the disease's incidence, though there are still many inconsistencies regarding the impact of specific dietary items. Among the dietary minerals, calcium intake may play a crucial role in the prevention. The purpose of this study was to assess the effect of intake of higher levels of dietary calcium on the risk of developing of colorectal cancer, and to evaluate dose dependent effect and to investigate possible effect modification. A hospital based case--control study of 1556 patients (703 histologically confirmed colon and rectal incident cases and 874 hospital-based controls) was performed between 2000--2012 in Krakow, Poland. The 148-item semi-quantitative Food Frequency Questionnaire to assess dietary habits and level of nutrients intake was used. Data regarding possible covariates was also collected. After adjustment for age, gender, education, consumption of fruits, raw and cooked vegetables, fish, and alcohol, as well as for intake of fiber, vitamin C, dietary iron, lifetime recreational physical activity, BMI, smoking status, and taking mineral supplements, an increase in the consumption of calcium was associated with the decrease of colon cancer risk (OR = 0.93, 95%CI: 0.89-0.98 for every 100 mg Ca/day increase). Subjects consumed >1000 mg/day showed 46% decrease of colon cancer risk (OR = 0.54, 95%CI: 0.35-0.83). The effect of dietary calcium was modified by dietary fiber (p for interaction =0.015). Finally, consistent decrease of colon cancer risk was observed across increasing levels of dietary calcium and fiber intake. These relationships were not proved for rectal cancer. The study confirmed the effect of high doses of dietary calcium against the risk of colon cancer development. This relationship was observed across different levels of dietary fiber, and the beneficial effect of dietary calcium depended on the level of dietary fiber suggesting modification effect of calcium and fiber. Further efforts are needed to confirm this association, and also across higher levels of dietary fiber intake.
    Nutrition Journal 10/2013; 12(1):134. DOI:10.1186/1475-2891-12-134 · 2.60 Impact Factor
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    • "We found no evidence of association between rs1801725 (CASR) and measures of anthropometry, physical activity levels or other demographic indicators. Additionally, previous investigations of CASR polymorphisms have found evidence against associations with many traits including , vitamin D levels [61], osteoarthritis [19], osteoporosis [19] or hip BMD [19] [20], as well as no[19] or only modest [20] associations with lumbar spine BMD; however, there is some evidence that their effects on BMD may be modified by birth-weight [62]. Although a previous smaller study of 1252 females aged between 70 and Fig. 3. Meta-analyses for the associations between genotypes and chair rises. "
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    ABSTRACT: Background Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability. Methods As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90 + years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance. Results Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p = 0.05, n = 11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures. Conclusion Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
    Bone 10/2012; 52(1). DOI:10.1016/j.bone.2012.10.004 · 3.97 Impact Factor
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