Case-control studies involving only women showed reduced risk of colorectal cancer (126,127). This was not demonstrated in studies involving both men and women (128). No significant inverse association was observed

between calcium and vitamin D levels and the risk of colorectal cancer (125,128). The Women’s health initiative study was a randomized controlled trial, which showed that daily supplementation of calcium with vitamin D for seven years, had no effect on the incidence of colorectal cancer among postmenopausal women (129). In terms of Vitamin D levels, a meta-analysis by Garland et al. found Inhibitors,research,lifescience,medical an inverse association between circulating levels of 25- hydroxyvitamin D3 and the risk of colorectal cancer (130). Calcium was found to have protective effect on colorectal Inhibitors,research,lifescience,medical cancer risk in some prospective studies (131-133)

but not in others (134,135). Data from the HPFS and NHS cohorts showed that total, dietary and supplemented calcium reduced the risk of distal colon but not proximal cancer. Most of the risk reduction was achieved by calcium intake of 700-800 mg/day. A meta analysis of 10 cohort studies showed 22% reduction in the risk of colorectal cancer in those with higher intake of calcium (136). Regarding colorectal polyps, a three-year intervention study with calcium and antioxidants, found no effect on polyp growth but possibly a protective role against adenoma Inhibitors,research,lifescience,medical formation (137). Higher intake of calcium alone (138) or when HDAC inhibitor combined with Vitamin

D (139) was found to be protective against adenoma recurrence. In conclusion, Inhibitors,research,lifescience,medical data from case-control studies are inconsistent but cohort studies and meta-analyses provide evidence on the benefits of circulating, diet-derived and supplemented vitamin D and calcium. Further studies are needed to ascertain whether there is any sex predilection. On the basis of current evidence one could suggest Inhibitors,research,lifescience,medical intake of vitamin D at a dose of 1,000 IU per day which is regarded as safe, and attaining calcium intakes of 700-800 mg per day. Modest duration of sunlight exposure should be the sought to raise levels of 25-hydroxyvitamin D3. Diets rich in oily fish, shellfish, milk and dairy products contain high amounts of calcium and vitamin D. Polyphenols Polyphenols are a class of chemicals known for their numerous benefits especially their antioxidant effects (113,140,141), inhibition of cellular proliferation (142), induction of cell cycle arrest (143), interaction with apoptotic pathways and antiangiogenic and antimetastatic properties (144). They are divided in five classes; flavonoids, phenolic acids, ligans, stillbenes and others. The most important dietary sources of polyphenols are fruits, vegetables, seeds, and beverages such as fruit juice, green tea, coffee, cocoa drinks, red wine, and beer. The chemoprotective role of polyphenols against cancer has been extensively studied.