Kiyonori Kuriki

Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors

To clarify preventive effects of n-3 polyunsaturated fatty acids (PUFAs) against colorectal carcinogenesis, we performed a dietary intervention in patients polypectomized for colorectal adenomas/tumors. For the former the following dietary advice was given: (1) decrease intake of fat from 30 to 20% of the total; (2) decrease consumption of n-6PUFAs containing foods, and increase intake of n-3 PUFAs for 2 years. For the comparison group only decreased intake of fat (30-20%) was recommended. Samples of normal sigmoid colon mucosa, obtained by colonoscopic check once a year during the intervention period, were used to investigate COX-2, cell proliferation (Ki67 expression), p53, Bcl-2 and Bax by immunostaining and determine the apoptosis index (AI) by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) in 21 and 20 patients in experimental and comparison groups, respectively, who completed the 2 years of the intervention. After 24 months, the AI and positive cells of Bax and the ratio of Bax/Bcl-2 in normal sigmoid colon mucosa for the experimental group was significantly increased, whereas this change was not found in comparison group. These observations demonstrated for the first time that increased intake of n-3 PUFAs promotes apoptosis of normal colon mucosa in human which is related to effect on Bax or the balance of Bax and Bcl-2.

Dietary risk factors for colon and rectal cancers: a comparative case-control study.

BACKGROUND In Japan, the incidence rate of colon cancer has more rapidly increased than that of rectal cancer. The differential secular trends may be due to different dietary factors in the development of colon and rectal cancers. METHODS To compare dietary risk factors between colon and rectal cancers, we undertook a case-control study at Aichi Cancer Center Hospital, Japan. Subjects were 507 patients with newly diagnosed colon (n = 265) and rectal (n = 242) cancers, and 2,535 cancer-free outpatients (controls). Intakes of nutrients and food groups were assessed with a food frequency questionnaire, and multivariate-adjusted odds ratios (ORs) were estimated using unconditional logistic models. RESULTS We found a decreasing risk of colon cancer with increasing intakes of calcium and insoluble dietary fiber; the multivariate ORs across quartiles of intake were 1.00, 0.90, 0.80, and 0.67 (trend p = 0.040), and 1.00, 0.69, 0.64, and 0.65 (trend p = 0.027), respectively. For rectal cancer, a higher consumption of carotene and meat was associated with a reduced risk; the corresponding ORs were 1.00, 1.10, 0.71, and 0.70 for carotene (trend p = 0.028), and 1.00, 0.99, 0.68, and 0.72 for meat (trend p = 0.036). Carbohydrate intake was positively correlated with the risk of rectal cancer (ORs over quartiles: 1.00, 1.14, 1.42, and 1.54; trend p = 0.048). This association was stronger in women, while fat consumption was inversely correlated with the risk of female colon and rectal cancers. CONCLUSIONS Dietary risk factors appear to considerably differ between colon and rectal cancers.

Breast cancer risk and erythrocyte compositions of n‐3 highly unsaturated fatty acids in Japanese

Dietary intake of fish rich in n‐3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been proposed to decrease cancer risk. In contrast to results from laboratory studies, however, protective effects for breast cancer have proved equivocal in epidemiological studies. In the present case‐control study, we examined associations between breast cancer risk and fatty acid compositions in erythrocyte membranes as biomarkers for those intakes. Dietary information and blood samples were collected from 103 incident breast cancer cases and 309 non‐cancer controls (matched by age and season) and erythrocyte fatty acids were measured using accelerated solvent extraction and gas‐liquid chromatography. Dietary intake of n‐3 HUFAs demonstrated a negative association with risk (the highest to the lowest tertile, odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27–0.98; ptrend < 0.05), but there was no association with those of saturated fatty acids (SFAs) and meat. Moreover, risk was inversely associated with erythrocyte compositions of EPA (OR, 0.27; 95% CI, 0.14–0.53; ptrend < 0.0001), DHA (OR, 0.06; 95% CI, 0.02–0.16; ptrend < 0.0001) and n‐3 HUFAs (OR, 0.11; 95% CI, 0.05–0.24; ptrend < 0.0001), and positively with that of SFAs (OR, 12.29; 95% CI, 4.94–30.57; ptrend < 0.0001) and the ratio of SFAs/n‐3 HUFAs (OR, 14.65; 95% CI, 5.67–37.82; ptrend < 0.0001). In conclusion, we showed that erythrocyte compositions of specific fatty acids derived from fish intake, as biomarkers, are associated with lower risk of breast cancer, but further studies are needed to investigate mechanisms linked to the etiology.

Risk of Colorectal Cancer Is Linked to Erythrocyte Compositions of Fatty Acids as Biomarkers for Dietary Intakes of Fish, Fat, and Fatty Acids

Consumption of fish rich in n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid, is suggested to reduce colorectal cancer risk through inhibition of the arachidonic acid (AA) cascade related to tumorigenesis and cell proliferation. High intake of saturated fatty acids (SFAs) may increase the risk. To examine associations between colorectal cancer risk and fatty acid compositions in erythrocyte membranes, as biomarkers for dietary intakes of fish, fat, and fatty acids, we conducted a case-control study with 74 incident cases and 221 noncancer controls (matched by age, sex, and season of sample collection). Erythrocyte fatty acids were measured using an accelerated solvent extraction and a gas-liquid chromatography. Colorectal cancer had no association with dietary intakes of meat, fish, fat, and fatty acids. However, the risk was inversely associated with erythrocyte compositions of docosahexaenoic acid, AA, and PUFAs [the highest to the lowest tertile, odds ratios, 0.36, 0.42, and 0.15; 95% confidence intervals, 0.14-0.93, 0.18-0.95, and 0.05-0.46; Ptrend < 0.05, respectively] and positively with those of palmitic acid, SFAs, and the ratio of SFAs/PUFAs (odds ratios, 6.46, 8.20, and 9.45; 95% confidence intervals, 2.41-17.26, 2.86-23.52, and 2.84-31.43; Ptrend < 0.005, respectively). In conclusion, we could clearly show decreased and increased risks for colorectal cancer related to PUFAs and SFAs compositions in erythrocyte membranes, respectively, but further research is needed to investigate the discrepancy between our findings and the generally accepted role of the AA cascade. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1791–8)

Relative validity of a semi-quantitative food frequency questionnaire versus 28-day weighed diet records in Japanese female dietitians

Objective: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs).Subjects and methods: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996–1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians.Results: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearsons de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum–median–maximum) ranged from 0.17 (beverages)–0.52 to 0.74 (rice), and Spearmans rank CCs with energy-adjustment ranged from 0.28 (confectionery)–0.42 to 0.68 (rice). Respective Pearsons CCs for intakes of nutrients were 0.28 (PUFAs)–0.51 to 0.73 (magnesium), and Spearmans rank CCs ranged from 0.23 (n-3 PUFAs)–0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement.Conclusions: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease.Sponsorship: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242).European Journal of Clinical Nutrition (2001) 55, 735–742

Associations between 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population.

Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case‐control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28–2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86–2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09–0.81) and rectal cancer (OR = 0.43, 95% CI 0.23–0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09–0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86–6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73–3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram‐years) may be also associated with colon or rectal cancer risk.

Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: A case‐control study in Chinese population

A case‐control study of 164 lung adenocarcinoma (AC) patients with 181 age‐ and gender‐matched healthy controls was conducted in order to assess any associations between glutathione‐S‐transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cyto‐chrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340–0.837)]. Furthermore, 3.0‐fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa1 wild type versus those with combined GSTM1 non‐null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC. (Cancer Sci 2003; 94: 448–452)

Discrepancies in dietary intakes and plasma concentrations of fatty acids according to age among Japanese female dietitians.

Objective: To clarify the influences of age on dietary intakes and plasma concentrations of fatty acids (FAs) in Japanese female dietitians.Subjects and methods: In autumn 1996, we estimated dietary FA intakes based on 7 day weighed diet records and analyzed plasma FA concentrations in 79 healthy Japanese female dietitians, and investigated their relationships with age, dividing into three age groups (young (32–42 y), middle-aged (43–50 y) and elderly (51–66 y)).Results: Dietary intakes of total FA, saturated FAs, monounsaturated FAs, n-3 polyunsaturated FAs (PUFAs) and α-linolenic acid (18:3n-3) were significantly highest in the middle-aged group, and lowest in the elderly. Similar trends were observed for dietary intakes of n-6 PUFAs and linoleic acid (18:2n-6), but there were no differences with regard to eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3) and n-3 highly unsaturated FAs (HUFAs=EPA+22:5n-3+DHA). On the other hand, plasma concentrations of all FAs except for arachidonic acid (20:4n-6) demonstrated positive correlations with age. Moreover, plasma concentrations of EPA in all age groups, DHA in the elderly and n-3 HUFAs in the middle-aged and the elderly were all positively correlated with dietary intakes.Conclusions: We should take into account the influence of age on dietary habit and lipid metabolism when interpreting associations between dietary FA intakes and plasma FA concentrations.Sponsorship: This study was supported in part by a grant-in-aid from the Ministry of Education, Science, Sports, Culture and Technology, Japan (06454242).

Validation study of fatty acid consumption assessed with a short food frequency questionnaire against plasma concentration in middle-aged Japanese people

Objective: To assess the relative validity of data for consumption of fatty acids (FAs) measured with a short food frequency questionnaire (FFQ) in comparison with plasma concentration of FAs. Design: In this cross-sectional study, completed FFQs were secured from 177 (92 male and 85 female) employees working for a company in August 2001. Intake of FAs was assessed with the FFQ, and the values were validated against FA concentration in plasma in overnight-fasting blood. Results: Mean9/SD daily intakes of total fatty acids (TFAs) were 44.49/8.0 g day-1 for men and 42.99/7.2 g day-1 for women. Plasma concentration of TFAs were 12.739/3.78 mmol l-1 for men and 10.549/1.75 mmol l-1 for women. Spearman’s rank correlation coefficients, unadjusted and energy-adjusted by the energy-density method and residual method, for n-3 highly unsaturated fatty acids (HUFAs) were 0.37 (p<0.001), 0.38 (p<0.001) and 0.40 (p<0.001) for men, and 0.41 (p<0.001), 0.26 (p<0 .01) and 0.29 (p<0.01) for women, respectively. Conclusions: Relative validity values of data for intake of n-3 polyunsaturated fatty acids (PUFAs) for women and n-3 HUFAs in both genders, assessed with the FFQ compared with FA concentration in plasma, were moderate, but no significant associations were found for saturated fatty acids, monounsaturated fatty acids or n-6 PUFAs. Keywords: fatty acids; food frequency questionnaire; plasma concentration; relative validity

Effect of dietary antioxidants and risk of oral, pharyngeal and laryngeal squamous cell carcinoma according to smoking and drinking habits

Several intervention trials and prospective studies have reported that β‐carotene supplementation is not associated with a decreased risk of several cancers among smokers and drinkers, and that it may even have adverse effects in these groups. The relationship between dietary antioxidant intake and the risk of head and neck squamous cell carcinoma (HNSCC) has been examined intensively, but little is known about the effects of antioxidants on HNSCC with respect to smoking and drinking habits. Here, we conducted a case‐control study of 385 histologically confirmed cases of HNSCC (193 oral, 132 pharyngeal and 60 laryngeal), excluding nasal and paranasal cancer, and 1925 age‐matched and sex‐matched cancer‐free outpatient controls using data from the Hospital‐based Epidemiologic Research Program at Aichi Cancer Center, Japan. The intake of nutrients and food groups was assessed with a food frequency questionnaire, and multivariate‐adjusted odds ratios for cancer were estimated for smoking and drinking habits using logistic models. The results showed an overall inverse association between the intake of dietary antioxidants, including carotene, and vitamins C and E, and risk of HNSCC. The protective effect of these antioxidants was seen in both men and women. High consumption of antioxidants was associated with a decreased risk of HNSCC among smokers, drinkers and those with both smoking and drinking habits. These findings suggest that dietary antioxidant intake prevents HNSCC in smokers and drinkers. (Cancer Sci 2006; 97: 760–767)