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.

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.

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.

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.