Sugars, sucrose and colorectal cancer risk: the Fukuoka colorectal cancer study.

OBJECTIVE: A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. METHODS: The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. RESULTS: Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. CONCLUSION: Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.

Estrogen receptor-ß gene polymorphism and colorectal cancer risk: effect modified by body mass index and isoflavone intake.

Estrogen receptor (ER)-ß signaling has generally been implicated in protection against colorectal cancer. The ER-ß gene cytosine-adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community-based case-control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein-labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥ 22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age-adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m(-2)) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism.

Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.

Microsomal epoxide hydrolase (EPHX1) plays an important role in the activation and detoxification of polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Polymorphisms in exon 3 (Y113H) and exon 4 (H139R) of the EPHX1 have been associated with enzyme activity. We investigated the risk of colorectal cancer in relation to the EPHX1 Y113H and H139R polymorphisms and assessed effect modifications of cigarette smoking and the other covariates. The interaction between the EPHX1 polymorphisms and selected genetic polymorphisms was also examined. We used data from Fukuoka Colorectal Cancer Study, a community-based case-control study, including 685 cases and 778 controls. In-person interviews were conducted to assess lifestyle factors. The EPHX1 Y113H and H139R polymorphisms were determined by the TaqMan assay and the polymerase chain reaction-restriction fragment length polymorphism, respectively. Neither of the two polymorphisms nor the imputed EPHX1 phenotype was associated with colorectal cancer risk. Cigarette smoking and alcohol intake showed no effect modification on the association with the EPHX1 polymorphisms or the imputed EPHX1 phenotype. Increased risks of colorectal cancer associated with the 113Y allele and imputed EPHX1 phenotype were observed among individuals with high body mass index (BMI; ≥25.0 kg/m(2)), but not among those with low BMI (<25.0 kg/m(2)). The risk decreased with an increasing number of the 139R allele in the null genotypes of GSTM1/GSTT1. It is unlikely that the EPHX1 polymorphisms play an important role in colorectal carcinogenesis. The observed interactions of the EPHX1 polymorphisms with BMI and the GSTM1/GSTT1 genotypes warrant further investigation.

Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease.

BACKGROUND: The aim of this study was to explore the associations between the prevalence of chronic kidney disease (CKD) and polymorphisms in the genes encoding matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs degrade extracellular matrix proteins in the glomerulus, and play important roles in kidney disease progression. METHODS: DNA samples from 3,309 subjects aged 35-69 years were genotyped for 10 potentially functional polymorphisms in MMP and TIMP genes. The prevalence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) was compared among the genotypes. RESULTS: The prevalence of CKD decreased significantly with the number of minor alleles in MMP9 C-1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT compared with CC; p for trend = 0.023) and MMP9 R668Q (ORs, 0.79 for RQ and 0.64 for QQ compared with RR; p for trend = 0.024). The haplotype MMP9 -1562T/279R/668Q showed a reduced risk for CKD compared with the most common -1562C/279R/668R (OR 0.77, p = 0.008), and the genotype combination -1562TT/ 279RR/668QQ showed a halved risk for CKD compared with major allele homozygous -1562CC/279RR/668RR (OR 0.53, p = 0.091). CONCLUSION: The potentially functional polymorphisms of MMP9 were associated with the prevalence of CKD in a large Japanese population. These genotypes have been reported to increase MMP9 expression, supporting the hypothesis that MMP-9 has a protective role in the progression of kidney diseases.

Dietary intakes of retinol, carotenes, vitamin C, and vitamin E and colorectal cancer risk: the Fukuoka colorectal cancer study.

It has long been a matter of interest whether antioxidant vitamins are protective against colorectal cancer as well as human cancers in general, but epidemiological evidence is inconclusive. We investigated associations of dietary intakes of retinol and antioxidant vitamins with colorectal cancer risk in 816 incident cases of histologically confirmed colorectal cancer and 815 controls randomly selected for the Fukuoka colorectal cancer study in Japan. Dietary intakes were assessed by a PC-assisted interview regarding 148 food items. Statistical adjustment was made for body mass index, physical activity, calcium, and n-3 fatty acid intake and other factors. Retinol intake was significantly, inversely associated with colorectal cancer risk; the odds ratio for the highest vs. lowest was 0.55 (95% CI: 0.35, 0.88; P (trend) = 0.01) in women, but a modest increase in the risk was observed among men with the highest intake of retinol. Liver was the major source of retinol intake and showed similar associations with colorectal cancer risk in men and women. Intake of carotenes, vitamin C, and vitamin E were not related to colorectal cancer risk in either men or women. The study did not support a hypothesis that dietary intake of antioxidant vitamins is protective in the development of colorectal cancer.

Behavioral and clinical correlates of high-sensitivity C-reactive protein in Japanese men and women.

BACKGROUND: Inflammation has been implicated in the pathogenesis of cardiovascular disease, type 2 diabetes mellitus and cancer. Serum concentration of high-sensitivity C-reactive protein is a good biomarker of chronic low-grade inflammation. Few studies have evaluated relative importance of behavioral and clinical covariates of high-sensitivity C-reactive protein in Japanese population. METHODS: The study subjects were men and women aged 49-76 years from the cohort study of lifestyle-related diseases between February 2004 and July 2006. Analysis of covariance and multiple linear regression analysis were used to estimate geometric means of high-sensitivity C-reactive protein and trends of association. RESULTS: Smoking, body mass index, hypertension, type 2 diabetes mellitus, elevated non-high density lipoprotein cholesterol, prudent dietary pattern were independently associated with serum high-sensitivity C-reactive protein in both men and women. High-sensitivity C-reactive protein concentrations were lowest in men with a moderate intake of alcohol (<30 mL/day). In men, smoking and body mass index accounted for 28% and 26% of the variation in high-sensitivity C-reactive protein, respectively, while body mass index accounted for 60% of the variation of high-sensitivity C-reactive protein in women. CONCLUSIONS: Smoking and body mass index in men, and body mass index in women, were major correlates of serum high-sensitivity C-reactive protein in Japanese people.

No effect modification of serum bilirubin or coffee consumption on the association of gamma-glutamyltransferase with glycated hemoglobin in a cross-sectional study of Japanese men and women.

BACKGROUND: Oxidative stress has been implicated in the development of type 2 diabetes mellitus. Bilirubin is a potent endogenous antioxidant, and coffee is a major source of exogenous antioxidants. Serum gamma-glutamyltransferase (GGT), a marker of oxidative stress, is a strong predictor of the risk of type 2 diabetes mellitus. This study evaluated the effect modification of bilirubin and coffee consumption on the association of serum GGT with glycated hemoglobin (HbA1c) and the combined effect of bilirubin and coffee on HbA1c concentrations. METHODS: The subjects were 4492 men and 6242 women aged 49-76 years who participated in the baseline survey of an on-going cohort study on lifestyle-related diseases in Fukuoka, Japan. Geometric means of HbA1c were examined according to quartile categories of GGT, with stratification by serum total bilirubin (≥ 0.6 mg/dL versus less in men and ≥ 0.5 mg/dL versus less in women) and coffee consumption (< 1, 1-3 and ≥ 4 cups of per day). Statistical adjustment was made for age, smoking, alcohol use and body mass index by using analysis of covariance. RESULTS: HbA1 concentrations increased progressively with increasing levels of GGT in both men and women. The increasing trend of HbA1c concentrations associated with GGT did not differ by either bilirubin status or coffee consumption. Both men and women with high bilirubin had consistently lower concentrations of HbA1c across the GGT quartiles. Higher coffee consumption was associated with lower concentrations of HbA1c in women with low bilirubin (trend P = 0.04), but not with high bilirubin (trend P = 0.37). There was no such association between coffee and HbA1c in men with either low or high bilirubin levels. CONCLUSIONS: Bilirubin is possibly protective against deterioration of glucose metabolism. Further studies are needed regarding the combined effect of bilirubin and coffee on glucose metabolism.

Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan.

BACKGROUND: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. METHODS: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. RESULTS: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). CONCLUSIONS: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.

Neuroticism and extraversion personality traits, health behaviours, and subjective well-being: the Fukuoka Study (Japan).

PURPOSE: We evaluated personality dimensions captured by an abbreviated 8-item questionnaire and examined associations of the personality traits with health behaviours and subjective well-being (SWB) measures. METHODS: The subjects were 11,554 participants in the Kyushu University Fukuoka Cohort Study who completed a self-administered questionnaire inquiring health behaviours, morbidity, personality, and SWB. Personality was assessed by using a questionnaire appeared to capture neuroticism and extraversion traits, and SWB-related variables were assessed with 3 single-item questions. RESULTS: Neuroticism was negatively and extraversion was positively associated with BMI. Extraversion, but not neuroticism, was positively associated with smoking and alcohol drinking. After multivariate adjustment, neuroticism was strongly associated with each of 3 SWB measures. The multivariate-adjusted odds ratios for the highest versus lowest quintile of neuroticism were 6.09 (95% confidence interval [CI], 5.05-7.33) for perceived stress; 0.21 (95% CI, 0.18-0.25) for good health condition; and 0.26 (95% CI, 0.22-0.31) for life satisfaction. Extraversion showed no clear association with the SWB measures. CONCLUSIONS: The neuroticism and extraversion scales were associated with health behaviours and BMI differently. The neuroticism scale, but not the extraversion scale, was strongly associated with higher perception of stress, poorer perceived health, and lower satisfaction with life in a Japanese population.

Soy food and isoflavone intake and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

OBJECTIVE: It has been suggested that soy food and isoflavone intake may be protective against the risk of colorectal cancer. However, epidemiologic evidence remains sparse and inconsistent. We addressed this issue in the Fukuoka Colorectal Cancer Study. MATERIAL AND METHODS: The study subjects were the 816 incident cases of histologically confirmed colorectal cancer and 815 community controls. Intakes of soy foods and isoflavones were assessed by in-person interview using a computer-assisted dietary method. Logistic regression analysis was applied to estimate odds ratio (OR) and 95% confidence interval (CI) of colorectal cancer with adjustment for dietary intakes of calcium and n-3 polyunsaturated fatty acids as well as for body mass index, physical activity, alcohol use, and other lifestyle factors. RESULTS: Energy-adjusted intakes of soy foods (dry weight) and isoflavones were inversely associated with colorectal cancer risk in men and postmenopausal women, but not in premenopausal women. The multivariate-adjusted OR for the highest versus lowest quintile was 0.65 (95% CI 0.41-1.03, p for trend = 0.03) for soy foods and 0.68 (95% CI 0.42-1.10, p for trend = 0.051) for isoflavones in men. The corresponding values for postmenopausal women were 0.60 (95% CI 0.29-1.25, p for trend = 0.053) and 0.68 (95% CI 0.33-1.40, p for trend = 0.049). The site-specific analysis showed inverse associations of soy foods (p for trend = 0.007) and isoflavones (p for trend = 0.02) with rectal cancer in men. CONCLUSION: The findings add to epidemiologic evidence for protective effects of soy foods and isoflavones in colorectal carcinogenesis.

Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

BACKGROUND: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. METHODS: We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. RESULTS: In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and > or = 800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with > or = 400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction = 0.06) or significant interaction (Pinteraction = 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk. CONCLUSIONS: Cigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation.

Dietary patterns and colorectal cancer in a Japanese population: the Fukuoka Colorectal Cancer Study.

Few studies have addressed the relation between dietary patterns and colorectal cancer in Japan. We investigated dietary patterns in relation to colorectal cancer risk in a community-based case-control study. The association with dietary patterns was also examined for different sites of colorectal cancer. Data were derived from the Fukuoka Colorectal Cancer Study, including 800 cases and 775 controls interviewed from September 2000 to December 2003. The cases were admitted to one of the participating hospitals for the first surgical treatment during this period. We identified dietary patterns using principal component analysis of intakes of twenty-nine items of food groups and specific foods. Quartile categories of each dietary pattern were used, and non-dietary lifestyle factors and total energy intake were adjusted for in the analysis. We identified three dietary patterns: prudent, high-fat and light-meal patterns. The prudent dietary pattern characterised by high intakes of vegetables, fruits, seafoods and soya foods showed a nearly significant protective association with the overall risk of colorectal cancer (trend P = 0.054), and it was statistically significantly related to a decreased risk of distal colon cancer (trend P = 0.002), but not to that of either proximal colon or rectal cancer. The high-fat and light-meal dietary patterns were not materially related to the overall or site-specific risk of colorectal cancer. In summary, a prudent dietary pattern was associated with a decreased risk of colorectal cancer, especially with that of distal colon cancer, in a fairly large case-control study in Japan.

Dietary fiber, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

OBJECTIVE: Despite much evidence from laboratory work, epidemiological evidence remains elusive regarding the role of dietary fiber in colorectal carcinogenesis. We investigated associations of dietary fiber and source foods with colorectal cancer risk in the Fukuoka Colorectal Cancer Study, a community-based case-control study. MATERIAL AND METHODS: The study subjects were 816 incident cases of colorectal cancer and 815 community controls. Nutrient and food intakes were estimated on the basis of a computer-assisted interview regarding 148 dietary items. Odds ratios of colorectal cancer according to quintile categories of energy-adjusted intakes of dietary fiber and food groups were obtained with adjustment for non-dietary factors and dietary intakes of calcium and n-3 fatty acids. RESULTS: Total, soluble and insoluble dietary fibers were not measurably associated with overall risk or subsite-specific risk of colorectal cancer. By contrast, rice consumption was associated with a decreased risk of colorectal cancer (trend p = 0.03), particularly of distal colon and rectal cancer (trend p = 0.02), and high intake of non-rice cereals tended to be related to an increased risk of colon cancer (trend p = 0.07). There was no association between vegetable consumption and colorectal cancer, whereas individuals with the lowest intake of fruits tended to have an increased risk of colorectal cancer. CONCLUSIONS: The present study did not corroborate a protective association between dietary fiber and colorectal cancer, but suggested a decreased risk of distal colorectal cancer associated with rice consumption.

Genetic polymorphisms of CYP2E1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.

Cytochrome P450 2E1 (CYP2E1) is involved in the metabolic activation of a wide variety of potential carcinogens, and functional polymorphisms in the CYP2E1 gene have been investigated in relation to colorectal cancer. We examined the relation of the CYP2E1 RsaI and 96-bp insertion polymorphisms to colorectal cancer risk and the interaction between these polymorphisms and some lifestyle risk factors. Subjects were 685 incident cases of colorectal cancer and 778 community controls. Statistical adjustment was made for alcohol use, body mass index, physical activity, and other factors. The RsaI c2 allele was associated with a decreased risk of rectal cancer [adjusted odds ratio for at least one c2 allele, 0.71; 95% confidence interval (95% CI), 0.53-0.95], and an increased risk of rectal cancer was observed among individuals having one or two 96-bp insertion alleles (adjusted odds ratio, 1.40; 95% CI, 1.06-1.85). Individuals with two 96-bp insertion alleles showed a 2.28-fold increase in colon cancer risk (95% CI, 1.29-4.01). The two polymorphisms were in almost complete linkage disequilibrium (D' = 0.94). A positive association between alcohol intake and colorectal cancer was observed only in individuals without RsaI c2 allele (P(trend) = 0.03) or in those without 96-bp insertion allele (P(trend) = 0.009). Colon cancer risk was increased in relation to red meat intake only in individuals having one or two 96-bp insertion alleles (P(interaction) = 0.03). The present study suggests that variation in activity and inducibility of CYP2E1, in relation to alcohol or red meat intake, contributes to the development of colorectal cancer.

Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.

Epidemiologic evidence supporting a protective role of calcium and vitamin D in colorectal carcinogenesis has been accumulating in Western populations, but it is limited in Asian populations, whose intake of calcium is relatively low. We investigated the association of intakes of these nutrients with colorectal cancer risk in Japanese. Study subjects were participants of a large-scale case-control study in Fukuoka, Japan. Diet was assessed through interview regarding 148 dietary items by showing typical foods or dishes on the display of a personal computer. In a multivariate analysis adjusting for potential confounding variables, calcium intake was significantly, inversely associated with colorectal cancer risk (P for trend=0.01); the odds ratio for the highest versus lowest quintile of calcium intake was 0.64 (95% confidence interval, 0.45-0.93). Higher levels of dietary vitamin D were significantly associated with decreased risk of colorectal cancer among those who had fewer chances of sunlight exposure at work or in leisure (P for trend=0.02). A decreased risk of colorectal cancer associated with high calcium intake was observed among those who had higher levels of vitamin D intake or among those who had a greater chance of daily sunlight exposure, but not among those with medium or lower intake of vitamin D or among those with potentially decreased sunlight exposure. These results add to support for a joint action of calcium and vitamin D in the prevention of colorectal carcinogenesis.

Personality and colorectal cancer: the Fukuoka colorectal cancer study.

OBJECTIVE: Although personality factors, especially emotional suppression and loss-hopelessness, have been linked to the occurrence and progression of cancer, little is reported specifically on colorectal cancer. It has also been claimed that a 'hysterical' personality characterized by exaggerated emotional expressions, egocentricity and ambivalent connection may be protective from cancer. This community-based case-control study examined whether personality factors relevant to emotional suppression or loss-hopelessness are associated with an increased risk of colorectal cancer, and whether factors related to the hysterical personality are associated with a decreased risk. METHODS: The stress inventory (SI), a self-administered questionnaire to assess the possible disease-prone and other relevant personalities in Japanese, was completed by 497 patients with newly diagnosed colorectal cancer and 809 controls randomly selected in the Fukuoka area of Japan. RESULTS: After controlling for age, sex and residence using a logistic regression model, none of the SI scales relevant to emotional suppression ('unfulfilled needs for acceptance', 'altruism', 'rationalizing conflicts/frustrations') or loss-hopelessness ('low sense of control', 'object-dependence/loss', 'object-dependence/happiness') was related to colorectal cancer. On the other hand, two scales representing elements of the hysterical personality, 'object-dependence/ambivalence' and 'egoism' were protectively associated with risk. Additional adjustment for body-mass index and lifestyle factors did not materially change these associations. CONCLUSIONS: Although personalities relevant to the emotional suppression or loss-hopelessness may not be a risk factor for colorectal cancer in the Japanese population, ambivalent connection and egocentricity may be protective.

Colorectal polypectomy and risk of colorectal cancer by subsite: the Fukuoka Colorectal Cancer study.

BACKGROUND: Colorectal adenomas are well-established precursor lesions for colorectal cancer and removal of polyps is deemed to reduce the risk of colorectal cancer. However, benefit of colorectal polypectomy in routine practice is still uncertain. We therefore investigated subsite-specific risks of colorectal cancer in relation to history of colorectal polypectomy in a case-control study. METHODS: Both case patients and control subjects were residents aged 20-74 years in Fukuoka City and three adjacent areas. The case group comprised 840 patients undergoing surgery for a first diagnosis of colorectal cancer, while the control subjects were 833 residents who were selected in the community by two-stage random sampling. Past history of selected diseases, surgery and lifestyle factors were ascertained by in-person interview. Statistical adjustment was made for sex, 5-year age class, residence, smoking, alcohol drinking, physical activity, body mass index and parental history of colorectal cancer. RESULTS: Overall, 74 case patients (9%) and 85 control subjects (10%) reported a prior history of colorectal polyps, and 50 cases (6%) and 64 controls (8%) had a history of colorectal polypectomy. The adjusted odds ratio associated with colorectal polypectomy was 0.71 (95% confidence interval [CI] 0.48-1.06) for the overall risk of colorectal cancer. The corresponding values for cancer of the proximal colon, distal colon, and rectum were 1.68 (95% CI 0.98-2.88), 0.71 (95% CI 0.41-1.26) and 0.24 (95% CI 0.11-0.52), respectively. CONCLUSIONS: The findings indicate that colorectal polypectomy in current practice confers a decreased risk of rectal cancer and possibly of distal colon cancer.

Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.

Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.

A case-control study of colorectal cancer in relation to lifestyle factors and genetic polymorphisms: design and conduct of the Fukuoka colorectal cancer study.

A case-control study was designed to elucidate roles of dietary and other behavioral influences, in combination with genetic susceptibility factors (genetic polymorphisms), in colorectal carcinogenesis. Both cases and controls were residents in Fukuoka City and three adjacent areas. Cases were patients undergoing surgery for a first diagnosis of colorectal cancer at 8 hospitals in the study area, and controls were randomly selected in the community by frequency-matching with respect to the expected distribution by sex, age (10-year class), and residence. Dietary and other lifestyle factors were ascertained by in-person interview, and venous blood was obtained for genotyping and possible biochemical measurements. The cases were interviewed at each hospital during the period from 2000 to 2003, and controls were surveyed during the period from 2001 to 2002. A total of 840 cases of colorectal cancer and 833 controls were interviewed with participation rates of 80% for the cases and 60% for the controls. Informed consent to genotyping was obtained from 685 cases and 778 controls. Further details of the design and conduct are described with respect to methodological aspects.

Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.

One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.