study subjects were participants in a comprehensive health examination conducted at the hitachi health care center , ibaraki , japan , during which colorectal cancer screening and , on request , abdominal ct scanning were performed . abdominal ct scanning was introduced to encourage changes in lifestyle , such as diet and physical activity , by showing examinees a graphic image , together with estimated data , of their own abdominal fat accumulation . in practice , it was offered mainly to individuals who underwent chest ct scanning for the screening of lung cancer . nearly one - third of all individuals who underwent screening chose to receive abdominal ct assessment . compared with men who did not , those who underwent abdominal ct scanning were older ( 53 vs. 46 years ) , were more likely to be past smokers ( 35 vs. 22% ) , and tended to have a higher bmi ( 23.9 vs. 23.6 kg / m ) . in contrast , the two groups were similar in terms of alcohol drinking ( > 1 go [ 23 g ethanol]/day : 32 vs. 29% ) . a go is a conventional unit of alcohol intake in japan . during the 3-year period from april 2004 to march 2007 , 47,224 examinees underwent fecal occult blood testing , which is specified as the standard procedure for colorectal cancer screening in the japanese guidelines . owing to limitations in colonoscopy resources , individuals with a positive blood test were first invited to receive a barium enema in the health center , and only those with suspected polyp lesions were referred to a medical specialist for detailed examination by colonoscopy . of 3,521 ( 8% ) who had a positive test result , of these , 491 ( 28% ) with a finding suggesting colorectal neoplasia were referred to local clinics or hospitals for confirmation . of the 280 patients who were notified by the physicians consulted that they had colorectal neoplasia , the present case series consisted of the 86 with histologically confirmed adenoma and 22 with early - stage colorectal cancer ( carcinoma in situ or cancer invading within the submucosa ) who received abdominal ct scanning at the time of the health checkup . among patients with adenomas of known size ( n = 82 ) , regarding the location of cancer , 5 cases were in the ascending colon , 2 were in the transverse colon , 13 were in the sigmoid colon , 1 was in the rectum , and 1 was not specified . for each case subject , three control subjects matched by year of examination , sex , and age ( same age ) were randomly selected from among examinees who had undergone abdominal ct measurement and had a negative fecal occult blood test . no case or control informed consent was obtained from each examinee regarding the use of his or her data for research purposes . the protocol of the present study was approved by the ethics committee of the hitachi health care center . measurement of abdominal fat area with a ct scanner has been detailed elsewhere ( 17 ) . in brief , single slice imaging was done at the level of the umbilicus in the supine position using a redix turbo ct scanner ( hitachi medico , tokyo , japan ) . imaging conditions , which have changed since 2004 , were 120 kv , 50 ma , and a 5-mm slice thickness . visceral fat area , subcutaneous fat area , and waist circumference were calculated using the pc software application fatpointer ( hitachi medico ) . height and weight were measured using an automated scale ( tanita bf-220 ) with the patient wearing a light gown . bmi was calculated as the weight in kilograms divided by the square of height in meters . fasting plasma glucose was measured by the glucose electrode technique using an adams glucose ga-1170 ( arkray ) . fasting serum immunoreactive insulin ( microunits per milliliter ) was determined by an immunoenzymatic method using the axsym insulin assay ( abbott ) . homeostasis model assessment of insulin resistance ( homa - ir ) , an index of insulin resistance , was calculated as fasting glucose multiplied by fasting insulin divided by 405 . participants entered their responses to the questionnaire directly into a computer using a custom - designed data entry system . regarding smoking , the questionnaire inquired about smoking status and for ever - smokers it inquired about the duration and intensity of smoking . for alcohol consumption , the frequency of drinking and the amount of alcohol consumed per session was assessed in terms of go . subject characteristics were compared between case subjects with adenomas and their matched control subjects and between case subjects with cancer and their matched control subjects . in control subjects , pearson correlation coefficients were calculated to examine the linear associations between visceral fat area and other exposure variables . conditional logistic regression was used to assess the association of various obesity indexes ( abdominal total fat mass , visceral fat area , subcutaneous fat area , waist circumference , and bmi ) and measures of insulin resistance ( insulin , glucose , and homa - ir ) with colorectal neoplasia . odds ratios ( ors ) and 95% cis for the prevalence of colorectal adenoma or cancer were calculated for the second and third ( highest ) tertiles of exposure , with the lowest tertile used as reference . cutoff values for the exposure tertile were determined based on the distribution among control subjects for colorectal adenomas and cancer , respectively . analyses were performed with and without adjustment for smoking ( lifetime nonsmoker , ever - smoker with 1600 cigarette - years , or ever - smoker with > 600 cigarette - years ) , and alcohol consumption ( nondrinker , drinker consuming 1 go / day , or drinker consuming > 1 go / day ) . in analyses for the relation of insulin resistance to visceral fat area and blood markers , all analyses were performed using sas ( version 10 ; sas institute , cary , nc ) . measurement of abdominal fat area with a ct scanner has been detailed elsewhere ( 17 ) . in brief , single slice imaging was done at the level of the umbilicus in the supine position using a redix turbo ct scanner ( hitachi medico , tokyo , japan ) . imaging conditions , which have changed since 2004 , were 120 kv , 50 ma , and a 5-mm slice thickness . visceral fat area , subcutaneous fat area , and waist circumference were calculated using the pc software application fatpointer ( hitachi medico ) . height and weight were measured using an automated scale ( tanita bf-220 ) with the patient wearing a light gown . bmi was calculated as the weight in kilograms divided by the square of height in meters . fasting plasma glucose was measured by the glucose electrode technique using an adams glucose ga-1170 ( arkray ) . fasting serum immunoreactive insulin ( microunits per milliliter ) was determined by an immunoenzymatic method using the axsym insulin assay ( abbott ) . homeostasis model assessment of insulin resistance ( homa - ir ) , an index of insulin resistance , was calculated as fasting glucose multiplied by fasting insulin divided by 405 . participants entered their responses to the questionnaire directly into a computer using a custom - designed data entry system . regarding smoking , the questionnaire inquired about smoking status and for ever - smokers it inquired about the duration and intensity of smoking . for alcohol consumption , the frequency of drinking and the amount of alcohol consumed per session was assessed in terms of go . subject characteristics were compared between case subjects with adenomas and their matched control subjects and between case subjects with cancer and their matched control subjects . in control subjects , pearson correlation coefficients were calculated to examine the linear associations between visceral fat area and other exposure variables . conditional logistic regression was used to assess the association of various obesity indexes ( abdominal total fat mass , visceral fat area , subcutaneous fat area , waist circumference , and bmi ) and measures of insulin resistance ( insulin , glucose , and homa - ir ) with colorectal neoplasia . odds ratios ( ors ) and 95% cis for the prevalence of colorectal adenoma or cancer were calculated for the second and third ( highest ) tertiles of exposure , with the lowest tertile used as reference . cutoff values for the exposure tertile were determined based on the distribution among control subjects for colorectal adenomas and cancer , respectively . analyses were performed with and without adjustment for smoking ( lifetime nonsmoker , ever - smoker with 1600 cigarette - years , or ever - smoker with > 600 cigarette - years ) , and alcohol consumption ( nondrinker , drinker consuming 1 go / day , or drinker consuming > 1 go / day ) . in analyses for the relation of insulin resistance to visceral fat area and blood markers , all analyses were performed using sas ( version 10 ; sas institute , cary , nc ) . table 1 shows patient characteristics for colorectal adenoma and cancer and their respective control subjects . patients with colorectal adenomas were more likely to smoke and consume alcohol heavily than their matched control subjects . in contrast , they had levels of obesity and markers of insulin or insulin resistance similar to those of control subjects . patients with colorectal cancer were more likely to be smokers and alcohol drinkers than their matched control subjects and on average had a greater bmi , waist circumference , and visceral and subcutaneous fat area than control subjects . markers of insulin resistance were higher among patients with colorectal cancer than among their matched control subjects . in control subjects , visceral fat mass was highly correlated with other measures of obesity ( pearson correlation coefficients : waist circumference 0.82 , bmi 0.68 , and subcutaneous fat mass 0.58 ) , moderately with insulin ( 0.44 ) , and weakly with fasting glucose ( 0.18 ) . characteristics of study subjects data are means  sd unless stated otherwise . as shown in table 2 , the odds of having colorectal cancer were increased in subjects with a higher visceral fat mass , with multivariable - adjusted ors ( 95% ci ) for the lowest through highest tertiles of 1 ( reference ) , 2.17 ( 0.4510.46 ) , and 5.92 ( 1.2228.65 ) , respectively ( ptrend = 0.02 ) . in contrast , subcutaneous fat mass was materially unrelated to colorectal cancer prevalence , with a multivariable - adjusted or for the highest versus lowest tertile of 1.08 ( 0.294.00 ) . higher levels of bmi or waist circumference were also associated with increased prevalence of colorectal cancer , with multivariable - adjusted ors ( 95% ci ; ptrend ) for the highest versus lowest tertile of visceral fat area of 4.38 ( 0.8223.25 ; 0.09 ) and 2.03 ( 0.577.25 ; > , no association was seen with any measure of obesity , including visceral fat mass . associations of measures of obesity with the prevalence of adenoma and cancer in the colorectum * measured by abdominal ct at the umbilical level in supine position . additionally adjusted for bmi . as shown in table 3 , the odds of colorectal cancer tended to increase with increasing fasting plasma glucose concentration and , to a lesser extent , with increasing fasting plasma insulin concentration and homa - ir . multivariable ors ( 95% ci ; ptrend ) for the highest versus lowest tertiles of glucose , insulin , and homa - ir were 4.40 ( 0.9919.59 ; 0.04 ) , 1.84 ( 0.477.15 ; > additional adjustment for bmi attenuated the association with insulin and homa - ir but did not greatly change that with glucose . in contrast , no measurable association was seen between colorectal adenoma and any of the three blood measurements . associations of glucose , insulin , and homa - ir with the prevalence of adenoma and cancer in the colorectum adjusted for smoking and alcohol drinking . among participants in a health screening program who underwent abdominal ct measurement , we found increased odds of early colorectal cancer in subjects with greater visceral fat mass , but not in those with greater subcutaneous fat mass . in contrast , these associations were not observed for colorectal adenoma . to our knowledge , this study is the first to provide direct evidence of an association between visceral adiposity and colorectal cancer risk . the present association between greater visceral fat area and increased prevalence of colorectal cancer is consistent with earlier epidemiological data showing a link between colorectal cancer and waist circumference or waist - to - hip ratio ( 4,5 ) . this finding indicates that visceral but not subcutaneous adipose tissue disposition is involved in the promotion of colorectal carcinogenesis . among studies that have measured visceral fat area using ct scanning in association with colorectal neoplasia ( 610 ) contrary to expectations , this study showed a higher prevalence of colorectal cancer in subjects with low rather than high visceral fat area . the authors speculated that this finding might have been due to weight loss induced by cancer progression . in our study , cancer in subjects included in the analysis was all screening - detected and early stage , and thus the results were unlikely to have been influenced by cancer - induced weight loss . in contrast to the positive finding for colorectal cancer , we observed no association between any measure of obesity , including visceral fat area , and the prevalence of colorectal adenoma . findings among studies that have measured abdominal fat area using ct are mixed : a significant positive association with visceral adiposity in a japanese study ( 7 ) was subsequently both supported ( 9 ) and challenged ( 8,10 ) . further , in an ancillary study to the polyp prevention trial ( 6 ) , visceral fat area measured on ct was not associated with adenoma recurrence . the reason for this discrepancy among adenoma studies is not clear . given that smoking is a strong determinant of both the prevalence of colorectal adenoma ( 18 ) and body weight ( 19 ) , the null finding in our study might be attributable , at least in part , to the high proportion of subjects with a history of smoking ( 73% ) . the relation of obesity measures to colorectal adenoma might only be detected in populations with no or low - level exposure to smoking , as suggested by a positive finding among nonsmokers ( 7 ) . alternatively , if the major role of obesity in colorectal carcinogenesis is to enlarge existing adenomas , the present null finding may be ascribable to the small number of case subjects with large adenomas ( 10 mm : n = 15 ) . the insulin hypothesis has been proposed to explain the association between obesity or visceral adiposity and colorectal cancer ( 12,13 ) . prospective studies have shown an increased risk of colorectal cancer among individuals with higher levels of postprandial insulin ( 4 ) , c - peptide ( 20,21 ) , a measure of average insulin secretion , and fasting glucose ( 4 ) at baseline , although the association with fasting insulin was less clear ( 4 ) . in accordance with these data , we observed an increase , albeit without statistical significance , in the odds of colorectal cancer in subjects with higher levels of markers of insulin resistance , particularly fasting glucose . with regard to colorectal adenoma , although some studies have demonstrated an elevated risk among individuals with higher levels of fasting insulin ( 22 ) or fasting glucose ( 23 ) , our data do not support a role of insulin resistance in the development of colorectal adenoma . recently , tabuchi et al . ( 24 ) reported similar findings in health checkup participants who underwent total colonoscopy : hyperglycemia was associated with an increased risk of colorectal cancer , but not with colorectal adenoma . similarly , chung et al . ( 25 ) demonstrated that glucose concentrations were more strongly associated with colorectal cancer than with adenoma . further studies are required to determine whether insulin resistance and resulting conditions , including hyperinsulinemia and hyperglycemia , are more strongly involved in the development of cancer than in that of adenoma . the present study has several methodological advantages over previous studies that directly measured visceral adiposity accumulation using ct . control subjects were randomly selected from a population of screening participants , among whom the cases arose , and abdominal ct measurement was done before the diagnosis of colorectal neoplasia , precluding the possibility of bias in the selection of control subjects and assessment of exposure , both of which are major concerns in case - control studies . first , the number of case subjects with colorectal cancer was small ( n = 22 ) . nevertheless , we were able to detect a statistically significant association with visceral fat area . second , although the control subjects were selected from among examinees with a negative screening result , they were not confirmed to be polyp free and thus may have included patients with colorectal adenomas , leading to attenuation of the association . given the low probability that the control series included subjects with undetected cancer , however , we believe that the present estimates for cancer were not subject to serious bias . third , physical activity , a convincing protective factor for colorectal cancer ( 1 ) , was not controlled for in the analysis ; in any case , such control would not be methodologically valid if physical activity exerted an anticarcinogenic effect by decreasing visceral fat . finally , because the majority of study subjects were male employees working for a large - scale company in japan , the results may not be generalizable to populations with different backgrounds . in summary , the present study of screening participants who underwent abdominal ct scanning provides direct evidence for the hypothesis that visceral fat accumulation and insulin resistance promote carcinogenesis of the colorectum . because adipose tissue secretes various hormones that may play a role in the development and progression of cancer not only through their effect on insulin resistance but also by directly controlling cell proliferation , the biological mechanisms linking visceral fat disposition to cancer risk should be further explored .