CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men.

AIM: To investigate the role of functional genetic polymorphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied were CYP1A1 2A (rs 4646903), CYP1A1 2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other lifestyle factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1. A borderline significant interaction was observed for the combination of CYP1A1 2C and NQO1 (P = 0.051). The OR associated with CYP1A1 2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1 2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1 2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1 2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There was no measurable effect modification of smoking even regarding the combination of the genetic polymorphisms of the phase I and phase II enzymes. CONCLUSION: Combination of the CYP1A1 2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status.

Coffee consumption, serum γ-glutamyltransferase, and glucose tolerance status in middle-aged Japanese men.

BACKGROUND: Recently, coffee consumption has been related to decreased risk of type 2 diabetes mellitus (DM) among those with high levels of serum γ-glutamyltransferase (GGT). We examined the association between coffee and glucose tolerance, determined by a 75 g oral glucose tolerance test, and the effect modification of serum GGT on the association. METHODS: The study subjects were 5320 men aged 46-60 years who received a health examination at two Self-Defense Forces hospitals from January 1997 to March 2004. Those medicated for DM were excluded. Coffee consumption was classified into <1, 1-2, 3-4, and ≥5 cups/day. Statistical adjustment was made for age, body mass index, smoking, alcohol use, leisure-time physical activity, green tea consumption, parental diabetes, hospital, and rank in the Self-Defense Forces. RESULTS: Men with normal glucose tolerance, isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG/IGT, and type 2 DM numbered 3384, 398, 790, 348, and 400, respectively. The prevalence odds of isolated IGT, combined IFG/IGT, and type 2 DM, but not of isolated IFG, decreased with increasing consumption of coffee. An inverse association with coffee was observed for isolated IGT in both low (≤40 IU/L) and high (>40 IU/L) GGT groups, and for combined IFG/IGT and type 2 DM in the latter group. CONCLUSIONS: Coffee drinking is protective against glucose intolerance. A possible effect modification of GGT on the coffee-DM association warrants further studies.

Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk: the self defense forces study.

Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3' untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (≥30 mL/d), but not in those with low alcohol consumption (interaction P = 0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas.

Lack of influence of the ADH1B Arg47His genetic polymorphism on risk of colorectal adenoma in middle-aged Japanese men.

Alcohol consumption is one of the risk factors for colorectal cancers and adenomas. Since alcohol dehydrogenase is a key enzyme in alcohol metabolism, it may thus play a role in colorectal carcinogenesis. The present study was conducted to assess the association of a functional ADH1B Arg47His polymorphism with colorectal adenomas in a case-control study of male officials in the Self-Defense Forces who received a pre-retirement health examination at two Self-Defense Forces hospitals. The study subjects comprised 455 with colorectal adenomas and 1,052 controls without polyps, all of whom underwent total colonoscopy. Statistical adjustment was made for age, hospital, Self-Defense Forces rank, body mass index, cigarette-years, and alcohol consumption. There was no measurable association between the ADH1B Arg47His polymorphism and colorectal adenoma development. The adjusted odds ratio for individuals with the 47His/His genotype compared to those with individuals with 47Arg alleles was 1.18 (95% confidence interval 0.94-1.49). There was no influence of the level of alcohol consumption (interaction P = 0.84). In addition, there were no clear interactions of the ADH1B with ALDH2 Glu487Lys and MTHFR C677T with regard to the risk of colorectal adenoma. In conclusion, the present study suggested that the ADH1B Arg47His polymorphism does not contribute to the risk of colorectal adenoma in any subgroup of middle-aged Japanese men defined by alcohol drinking, as well as the ALDH2 Glu487Lys and MTHFR C677T genotypes.

Circulating vitamin D and colorectal adenomas in Japanese men.

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.

C-reactive protein and colorectal adenomas: Self Defense Forces Health Study.

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 (> or = 5 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.

Waist circumference and insulin resistance: a cross-sectional study of Japanese men.

BACKGROUND: Visceral obesity is positively related to insulin resistance. The nature of the relationship between waist circumference and insulin resistance has not been known in Japanese populations. This study examined the relationship between waist circumference and insulin resistance and evaluated the optimal cutoff point for waist circumference in relation to insulin resistance in middle-aged Japanese men. METHODS: Study subjects included 4800 Japanese men aged 39 to 60 years. Insulin resistance was evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship of waist circumference with HOMA-IR was assessed by use of adjusted means of HOMA-IR and odds ratios of elevated HOMA-IR defined as the highest quintile (>or=2.00). Receiver operating characteristics (ROC) curve analysis using Youden index and the area under curve (AUC) was employed to determine optimal cutoffs of waist circumference in relation to HOMA-IR. RESULTS: Adjusted geometric means of HOMA-IR and prevalence odds of elevated HOMA-IR were progressively higher with increasing levels of waist circumference. In the ROC curve analysis, the highest value of Youden index was obtained for a cutoff point of 85 cm in waist circumference across different values of HOMA-IR. Multiple logistic regression analysis also indicated that the AUC was consistently the largest for a waist circumference of 85 cm. CONCLUSION: Waist circumference is linearly related to insulin resistance, and 85 cm in waist circumference is an optimal cutoff in predicting insulin resistance in middle-aged Japanese men.

Genetic polymorphisms of CYP2E1 and risk of colorectal adenomas in the Self Defense Forces Health Study.

CYP2E1 is an enzyme involved in the metabolism of N-nitrosamines and other carcinogenic substances. Functional RsaI and 96-bp insertion polymorphisms in 5'-flanking region have drawn interest in relation to the risk of colorectal cancer. We investigated the relation of these genetic polymorphisms and colorectal adenoma, a well-established precursor lesion of colorectal cancer. Subjects were 455 cases of colorectal adenomas and 1,052 controls of normal colonoscopy among men receiving a preretirement health examination in the Self Defense Forces. Genotypes were determined by either PCR-RFLP or PCR method. Statistical adjustment was made for smoking, alcohol use, body mass index, physical activity, and others. Individuals with RsaI c2 allele showed a decreased risk of proximal colon adenomas; adjusted odds ratios (95% confidence interval) of proximal and distal adenomas for the c1/c2 or c2/c2 genotype versus c1/c1 was 0.61 (0.41-0.88) and 0.95 (0.71-1.27), respectively. CYP2E1 96-bp insertion allele was associated with an increased risk of large (> or = 5 mm) adenomas; adjusted odds ratios (95% confidence interval) of large and small adenomas for having at least one insertion allele were 1.41 (1.03-1.94) and 0.94 (0.71-1.25), respectively. A suggestive effect modification was noted for alcohol consumption on the association between RsaI polymorphism and proximal adenomas (P(interaction) = 0.09) as well as on the association between 96-bp insertion and large adenomas (P(interaction) = 0.05). These findings indicate that variation in activity and inducibility of CYP2E1 contribute to the development of colorectal carcinogenesis.

Adiponectin and colorectal adenomas: Self Defense Forces Health Study.

Adiponectin is an adipocyte-derived protein with an insulin-sensitizing 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 high-molecular-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 microg/mL in cases and 5.63 microg/mL in controls (P = 0.13), and the corresponding values of HMW adiponectin were 2.47 microg/mL and 2.57 microg/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 (>or= 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.

Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: the Self Defense Forces Health Study.

Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX-2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX-2 polymorphisms (-1195G>A, -765G>C and 8160A>G) to colorectal adenomas in a case-control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non-significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of -1195G>A polymorphism and for the GC versus GG genotype of -765G>C polymorphism. None had the -765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either -1195G>A or -765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of -1195G, -765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99-1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04-2.38). Another haplotype of -1195A, -765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06-0.88). These findings add to evidence for the role of COX-2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes.

Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment.

BACKGROUND AND AIMS: Dietary therapy using phytosterols can reinforce statin treatment; however the value of a low-dose combination of those agents remains to be investigated. Plant sterols (PS), dissolved in diacylglycerol (DAG) oil, (PS/DAG) can be effective at a relatively low dose. The objective of the present study was to examine the effect of PS/DAG oil on blood cholesterol concentrations in hypercholesterolemic outpatients on low-dose pravastatin (10 mg/day). METHODS AND RESULTS: The patients (n=61) were randomly assigned to one of three groups, who consumed TAG (control), DAG or PS/DAG oil. The average intake of PS from the PS/DAG oil during the test period was significantly higher than that for TAG and DAG oils (502 vs. 49 and 38 mg/day, P<0.05). Significant cholesterol-lowering effects from the baseline were observed in the case of the PS/DAG oil treatment alone. Changes in low-density lipoprotein (LDL) cholesterol were inversely correlated with baseline serum campesterol concentrations (r=-0.560, P<0.05), but not baseline LDL cholesterol concentrations. In addition, serum apolipoprotein B concentrations were reduced to a greater extent in subjects with high versus low levels of baseline campesterol (-13.2 mg/dL vs. -3.1 mg/dL, P<0.05). Furthermore, there was a mild, but significant reduction in serum lipoprotein (a) concentration from the baseline (-5.9 mg/dL), which was correlated with the reduction in serum apolipoprotein B concentration (r=0.596, P<0.05). CONCLUSION: A low-dose combination of PS/DAG oil and pravastatin may be a useful strategy for further ameliorating blood cholesterol and lipoprotein (a) concentrations for hypercholesterolemic patients with a low response to pravastatin.

Dietary patterns and glucose tolerance abnormalities in Japanese men.

The Western dietary pattern appears to confer diabetes risk, but the role of dietary patterns in Asian populations remains unclear. We investigated the association between major dietary patterns and the glucose tolerance status of Japanese men. Abnormalities included impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. Subjects were 2106 Japanese men who were administered a 75-g oral glucose tolerance test at their preretirement health check-ups. Information about diet was obtained using a 74-item FFQ before the test. Three dietary patterns were generated by factor analysis: 1) a high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; 2) an animal food pattern; and 3) a Japanese pattern. We used logistic regression analysis to estimate odds ratios (OR) with adjustment for potential confounding variables. A significant inverse association was found for the high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern (P for trend < 0.0001); the OR of having a glucose tolerance abnormality (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) for the 2nd, 3rd, and 4th quartiles were 0.80 (95% CI = 0.62-1.04), 0.71 (95% CI = 0.54-0.92), and 0.51 (95% CI = 0.38-0.67), respectively, compared with the lowest quartile. The inverse association was consistent for each glucose tolerance abnormality as well as across subgroups stratified by risk factors for diabetes. The Japanese dietary pattern was positively associated with impaired glucose tolerance (P for trend = 0.048). A dietary pattern characterized by frequent consumption of dairy products and fruits and vegetables but low alcohol intake may be associated with a decreased risk of developing a glucose tolerance abnormality.

Genetic polymorphism of cholesterol 7alpha-hydroxylase (CYP7A1) and colorectal adenomas: Self Defense Forces Health Study.

Bile acids have long been implicated in colorectal carcinogenesis, but epidemiological evidence is limited. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme producing bile acids from cholesterol. A recent case-control study showed a decreased risk of proximal colon cancer associated with the CC genotype of the CYP7A1 A-203C polymorphism. The present study examined the relationship between the CYP7A1 A-203C polymorphism and colorectal adenoma, which is a well-established precursor lesion of colorectal cancer. The study subjects comprised 446 cases of colorectal adenomas and 914 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). The CYP7A1 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Statistical adjustment was made for age, hospital, rank in the SDF, smoking, alcohol use, body mass index, physical activity and parental history of colorectal cancer. The CYP7A1 polymorphism was not measurably related to the overall risk of colorectal adenomas. However, the CC genotype was associated with a decreased risk of proximal colon adenomas, but not of distal colon and rectal adenomas. Adjusted odds ratios of proximal colon adenomas (95% confidence intervals) for the AC and CC genotype versus AA genotype were 0.82 (0.54-1.24) and 0.56 (0.34-0.95), respectively. The findings add to evidence for the role of bile acids in colorectal carcinogenesis. The CC genotype of the CYP7A1 A-203C polymorphism probably renders lower activity of the enzyme synthesizing bile acids.

Relation of alcohol use and smoking to glucose tolerance status in Japanese men.

To investigate the relation of alcohol use and cigarette smoking to glucose tolerance status, we performed a cross-sectional study of 3038 male officials aged 46-59 years in the Self-Defense Forces. Glucose tolerance status was determined by a 75-g oral glucose tolerance test. A self-administered questionnaire was used to ascertain alcohol use, smoking habits, and other lifestyle characteristics. Statistical adjustment was made for parental history of diabetes, body mass index, and leisure-time physical activity. Alcohol use was positively associated with impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes mellitus each. The association was dose-dependent, with odds of each category of glucose intolerance increased even among those with moderate alcohol use. Cigarette smoking was not related to any categories of glucose intolerance. Alcohol use may confer increased risks not only of type 2 diabetes mellitus but also of preceding glucose intolerance status. Smoking does not seem to deteriorate glucose tolerance.

Genetic polymorphisms of methylenetetrahydrofolate reductase and aldehyde dehydrogenase 2, alcohol use and risk of colorectal adenomas: Self-Defense Forces Health Study.

Methylenetetrahydrofolate reductase is a key enzyme in folate metabolism, which affects DNA synthesis and methylation and is possibly linked to colorectal carcinogenesis. Alcohol and acetaldehyde have an adverse effect on folate metabolism. This study investigated the relationship of functional MTHFR C677T and ALDH2 polymorphisms to colorectal adenomas with reference to alcohol consumption in a case-control study of male officials in the Self-Defense Forces (SDF) who received a preretirement health examination at two SDF hospitals. The study subjects were 452 cases of colorectal adenoma and 1050 controls with no polyp who underwent total colonoscopy. Genotypes were determined by the PCR-RFLP method using genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index, cigarette-years and alcohol intake. Neither MTHFR C677T nor ALDH2 showed a measurable association with colorectal adenoma. While high alcohol consumption was associated with a moderately increased risk of colorectal adenoma, neither of the two polymorphisms showed a significant effect on the association between alcohol and colorectal adenoma. Individuals with the variant alleles ALDH2*2 and MTHFR 677T had a decreased risk of colorectal adenomas, showing adjusted odds ratios of 0.70 (95% confidence interval 0.49-1.00) for all adenomas and 0.57 (0.34-0.95) for large adenomas (> or = 5 mm), as compared to individuals with ALDH2*1/1 and MTHFR 677CC genotypes combined. The findings may be interpreted as suggesting that folate inhibits the growth of colorectal adenomas, but further confirmation is needed.

Dietary patterns and colorectal adenomas in Japanese men: the Self-Defense Forces Health Study.

The role of dietary patterns in colorectal carcinogenesis remains unclear in Asian populations. Using 1999-2002 data, the authors investigated the association between dietary patterns and colorectal adenomas in 1,341 Japanese men who underwent total colonoscopy. Information about diet was obtained using a 74-item food frequency questionnaire prior to the colonoscopy. Three dietary patterns were generated by factor analysis: 1) a high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; 2) an "animal food" pattern; and 3) a Japanese pattern. Logistic regression analysis was used to estimate the odds ratio of having colorectal adenomas with the adjustment for potential confounding variables including body mass index, smoking, alcohol, and leisure-time physical activities. A significant inverse association was found for the high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; the odds ratios for the second, third, and fourth quartiles were 0.97 (95% confidence interval: 0.70, 1.36), 0.71 (95% confidence interval: 0.50, 1.01), and 0.62 (95% confidence interval: 0.43, 0.90), respectively, compared with the lowest (p(trend) = 0.003). Similar associations were observed for larger adenomas or for each subsite of the colorectum. The Japanese and "animal food" patterns were not clearly associated with colorectal adenomas. A dietary pattern including greater consumption of dairy products and fruits and vegetables with low alcohol consumption may be associated with decreased risk of colorectal adenomas.

The metabolic syndrome is associated with increased risk of colorectal adenoma development: the Self-Defense Forces health study.

The metabolic syndrome, a cluster of metabolic abnormalities linked to insulin resistance, has attracted much interest as a risk factor for cardiovascular disease and type 2 diabetes. Hyperinsulinemia is also a postulated biological risk factor for colorectal carcinogenesis. We therefore here examined the relation between the metabolic syndrome and colorectal adenoma development. The study subjects were 756 cases of colorectal adenoma and 1751 controls with no polyps who underwent total colonoscopy during the period January 1995 to March 2002 at two Self Defense Forces (SDF) hospitals in Japan. The metabolic syndrome was defined with reference to abdominal obesity in combination with any two of the following conditions: elevated triglycerides (150 mg/dL); lowered HDL cholesterol (<40 mg/dL); elevated blood pressure (systolic blood pressure 130 mmHg and/or diastolic blood pressure 85 mmHg); and raised fasting glucose (110 mg/dL). Abdominal obesity was defined as a waist circumference of 85 cm or more(Japanese criterion) or 90 cm (Asian criterion). Statistical adjustment was made for age, hospital, and rank in the SDF. The metabolic syndrome was found to be associated with a moderately increased risk of colorectal adenomas whether either of the Japanese and Asian criteria was used; adjusted odds ratios with the Japanese and Asian criteria were 1.38 (95% confidence interval [CI] 1.13-1.69) and 1.48 (95% CI 1.13-1.93), respectively. Increased risk was more evident for proximal than distal colon or rectal adenomas, and was almost exclusively observed for large lesions (5 mm in diameter). Thus the metabolic syndrome appears to be an important entity with regard to the prevention of colorectal cancer, as well as cardiovascular disease and type 2 diabetes.

Plasma vascular endothelial growth factor level is elevated in patients with multivessel coronary artery disease.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been implicated in both angiogenesis and ischemia. However, the relationship between plasma VEGF level and coronary artery disease remains unknown. HYPOTHESIS: Plasma VEGF level may be associated with severe coronary artery disease and other cardiovascular risk factors. METHODS: We examined plasma VEGF concentration and coronary risk factors in 73 patients who underwent coronary angiography and 70 apparently healthy control subjects. According to the number of the three major coronary vessels with significant (> or = 75%) stenosis, we divided the patients into two groups: the mild stenosis group (0- and single-vessel disease, n = 36) and the severe stenosis group (double- and triple-vessel disease, n = 37). RESULTS: The log VEGF value of the severe stenosis group was significantly higher than that of the mild stenosis (p < 0.05) and control groups (p < 0.05). Furthermore, there was a significant positive trend in the log VEGF value according to the number of vessels with significant stenosis (p = 0.016). However, there was no significant difference in log VEGF value between the mild stenosis and control groups. Soluble vascular cellular adhesion molecule, soluble intracellular adhesion molecule, and other coronary risk factors were found to be associated with the presence of vessel stenosis. CONCLUSION: Unlike established coronary risk factors, the plasma VEGF level may be associated with only severe coronary ischemia such as multiple coronary vessel disease.

Relation of cigarette smoking and alcohol use to colorectal adenomas by subsite: the self-defense forces health study.

While smoking has consistently been shown to be related to increased risk of colorectal adenomas, few studies have addressed the association between smoking and site-specific colorectal adenomas. The reported association between alcohol use and colorectal adenomas has been inconsistent. We evaluated risks of adenomas at the proximal colon, distal colon, and rectum in relation to cigarette smoking and alcohol use, and their interaction. Subjects were 754 cases with histologically proven colorectal adenomas and 1547 controls with normal colonoscopy among male officials of the Self-Defense Forces (SDF) undergoing total colonoscopy at two SDF hospitals. Statistical adjustment was made for hospital, rank, body mass index, physical activity, and either smoking or alcohol drinking. Cigarette smoking was significantly associated with an increased risk of adenomas, regardless of the location of the adenomas, but the increased risk associated with smoking was more pronounced for rectal adenomas. Alcohol use was associated with moderately increased risks of distal colon and rectal adenomas, but not of proximal colon adenomas. Cigarette smoking, but not alcohol drinking, was associated with greater increases in the risk of large adenomas and of multiple adenomas across the colorectum. There was no measurable interaction of cigarette smoking and alcohol drinking on colorectal adenomas. The findings corroborate an increased risk of colorectal adenomas associated with smoking and a weak association between alcohol use and colorectal adenomas. Further studies are needed to confirm whether smoking is more strongly related to rectal adenomas, large adenomas, or multiple adenomas.