Accumulating evidence suggests that vitamin D has anticarcinogenic effects. However, it is unclear whether the nutrient is involved in the early stage of colorectal carcinogenesis. We examined the association between circulating vitamin D concentrations and colorectal adenomas in Japanese men. The study subjects comprised 656 cases of colorectal adenomas and 648 controls with normal colonoscopy among male self defense officials receiving a pre-retirement health examination between 1997 and 2004. Plasma or serum levels of 25-hydroxyvitamin D [25(OH)D] were measured using a radioimmunoassay method. Logistic regression analysis was used to obtain odds ratios (OR) and 95% confidence intervals (CI) with adjustment for potential confounding variables. Overall, there was no measurable association between circulating 25(OH)D concentrations and colorectal adenomas. When the analysis was restricted to subjects whose blood was taken during the winter season (November-April), the prevalence odds of colorectal adenomas for the highest versus lowest quartile of 25(OH)D was statistically significantly decreased (OR = 0.58; 95% CI = 0.34-0.99). The reduction was more pronounced for the rectum (OR = 0.22) and distal colon (OR = 0.47) than for proximal colon (OR = 0.70). During the summer season (May-October), higher levels of 25(OH)D were associated with an increased odds of small, but not large, adenomas. The present study adds to evidence that high levels of circulating vitamin D measured during darker season is associated with decreased prevalence of adenomas in the distal sites of the colorectum. (Cancer Sci 2010; 101: 1695-1700 T he protective role of vitamin D has recently drawn much interest in colorectal carcinogenesis.(1-3) Vitamin D has long been known to enhance intestinal absorption of calcium, (3) which has also been associated with decreased risk of colorectal cancer.(4) Natural sources of vitamin D are production in the skin by solar exposure, fish oil, and shiitake mushroom. The hypothesis that vitamin D is protective against colorectal cancer in humans was proposed on the basis of a geographical correlation between sunlight exposure and colon cancer mortality in the USA.(5) Subsequently, cohort and case-control studies have observed a fairly consistent, protective association between vitamin D intake and colon or colorectal cancer, as reviewed comprehensively elsewhere.(1) Furthermore, decreased risk of colon, rectal, or colorectal cancer has been observed in individuals with higher circulating 25(OH)D levels in several prospective studies (6)(7)(8)(9)(10)(11)(12) although not all studies have found such an association.(13) With regard to colorectal adenomas, a wellestablished precursor lesion of colorectal cancer, (14,15) six casecontrol studies have addressed the association with plasma or serum concentrations of 25(OH)D, reporting a protective association for adenoma prevalence (16)(17)(18) and recurrence (19,20) consistently with one exception. (21) Of particular interest is a recent observation that an inve...

Adiponectin is an adipocyte-derived protein with an insulinsensitizing action. Circulating levels of adiponectin are inversely correlated with obesity, especially abdominal obesity. Some studies have suggested that low levels of circulating adiponectin might be related to increased risk of colorectal cancer and adenomas. The present study examined the relationship between total and highmolecular-weight (HMW) adiponectin to colorectal adenomas in the Self Defense Forces (SDF) Health Study. The study subjects comprised 656 cases of colorectal adenomas and 648 controls with normal colonoscopy among men receiving a preretirement health examination at two Self Defense Forces hospitals. Total and HMW adiponectin were slightly lower in adenoma cases than in controls; geometric means of total adiponectin were 5.42 μ μ μ μg/mL in cases and 5.63 μ μ μ μg/mL in controls (P = 0.13), and the corresponding values of HMW adiponectin were 2.47 μ μ μ μg/mL and 2.57 μ μ μ μg/mL, respectively (P = 0.29). Regardless of adjustment for body mass index and other lifestyle factors, total adiponectin was unrelated to the risk of colorectal adenomas. Total adiponectin levels were inversely related to the risk of large adenomas (≥ ≥ ≥ ≥ 5 mm), but not of small adenomas, with a nearly statistically significant decreasing trend (P = 0.06). However, the inverse association was largely ascribed to body mass index and other lifestyle factors. HMW adiponectin showed no clear association with either overall or size-specific risk of colorectal adenomas. The study provided suggestive evidence for a protective association between adiponectin and large adenomas, but did not indicate a protective association independent of adiposity. (Cancer Sci 2008; 99: 781-786)A diponectin is an adipocyte-derived protein that is expressed specifically and abundantly in adipose tissue.(1,2)The primary known function of this molecule is an insulinsensitizing action, and decreased levels of adiponectin seem to be fundamentally involved in the development of insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome.(1-3) Paradoxically, circulating levels of adiponectin are inversely correlated with obesity, especially abdominal obesity.(2,4) It is thus of natural interest to examine the relationship between circulating levels of adiponectin and risk of obesity-related cancers. Increased risks of endometrial (5,6) and breast cancer (7,8) were consistently observed in women with low levels of circulating adiponectin in case-control studies. Low levels of circulating adiponectin have also been linked to increased risk of renal cell carcinoma.(9) Two prospective studies have addressed the relationship between plasma adiponectin levels and colorectal cancer risk; one study showed a decreased risk in men at the second to fifth quintiles compared with those at the lowest quintile, (10) but the other found no association between adiponectin and colorectal cancer.(11) A recent casecontrol study reported that plasma levels of adiponectin were substantially lower ...

Chronic inflammation has been implicated in colorectal carcinogenesis. Several studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer and adenomas, resulting in inconsistent findings. The present study examined the relationship between circulating levels of high-sensitivity CRP and colorectal adenomas. The study subjects comprised 646 cases of colorectal adenoma and 635 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces. Statistical adjustment was made for cigarette smoking, alcohol use, body mass index, physical activity, and other potential confounders. The multivariate-adjusted geometric means showed no measurable differences between adenoma cases and controls, but were higher among cases with larger adenomas (trend P = 0.03). Likewise, although the prevalence odds of colorectal adenomas did not differ according to CRP levels as categorized at the 30th, 60th, and 90th percentiles in the controls, higher levels of CRP were associated with a statistically significant increase in the prevalence odds of large adenomas (³5 mm), but not of small adenomas (<5 mm). The multivariate-adjusted odds ratios of large adenomas for the lowest to highest categories of CRP were 1.00 (referent), 1.81 (95% confidence interval 1.17-2.80), 1.61 (95% confidence interval 1.03-2.52), and 2.21 (95% confidence interval 1.28-3.84), respectively (trend P = 0.01). A positive association between CRP and prevalence odds of large adenomas was not modified by either smoking or overweight. These findings suggest that inflammation is linked to the growth of colorectal adenomas. (Cancer Sci 2009; 100: 709-714) C hronic inflammation has been implicated in carcinogenesis. (1,2) Inflammatory cytokines are considered to promote carcinogenesis by inducing oxidative DNA damage, stimulating cell proliferation and angiogenesis, and inhibiting apoptosis.(1,2) Particular interest has been drawn to the role of inflammation in colorectal carcinogenesis. Chronic inflammatory bowel diseases are known to confer increased risk of colorectal cancer, (3,4) and use of aspirin or non-steroidal anti-inflammatory drugs has consistently been related to reduced risk of colorectal adenomas and cancer in observational and intervention studies.(5-8) Recently, several prospective studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer risk, resulting in inconsistent findings. (9)(10)(11)(12)(13)(14)(15)(16) An increased risk of colorectal cancer associated with increased concentrations of CRP was first reported in the CLUE II study. (9) A positive association between CRP and colorectal caner risk was replicated in three subsequent studies, (10)(11)(12) but no such association was observed in four other studies. (13)(14)(15)(16) One of the latter studies even suggested a decreased risk associated with high concentrations of CRP. (13) Results are al...