Minatsu Kobayashi

Intake of Fish and n3 Fatty Acids and Risk of Coronary Heart Disease Among Japanese The Japan Public Health Center-Based (JPHC) Study Cohort I

Background— Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk. Methods and Results— To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41 578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990–1992 to 2001. After 477 325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]). Conclusions— Compared with a modest fish intake of once a week or ≈20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.

Salt and salted food intake and subsequent risk of gastric cancer among middle-aged Japanese men and women

Evidence on the association between salt intake and gastric cancer is sparse, especially in prospective studies. We conducted a population-based prospective study in Japan, where the majority of men has been infected with Helicobacter pylori. A total of 18 684 men and 20 381 women aged 40–59 years who reported their dietary habits and did not report any serious disease at baseline were followed from 1990 to 2001. A total of 486 cases, 358 men and 128 women, with histologically confirmed gastric cancer were documented among them. The quintile category of salt intake was dose-dependently associated with gastric cancer risk in men after adjusting for potential confounding factors (P for trend <0.001), while a trend was not clear in women (P for trend=0.48). Although stratification by study area, with varied salt intake and gastric cancer incidence, attenuated the observed clear associations with salt and salted foods, the frequency categories of highly salted foods such as salted fish roe and salted fish preserves were strongly associated with the risk in both sexes. Restriction of salt and salted food intake is a practical strategy to prevent gastric cancer in areas with high risk.

Single measurement of serum phospholipid fatty acid as a biomarker of specific fatty acid intake in middle-aged Japanese men

Objective: To assess the utility of serum phospholipid fatty acid (FA) levels as a biochemical indicator of habitual dietary fatty acid intake in Japanese, whose diet is characterized by low fat intake and high intake of n-3 polyunsaturated fatty acids (PUFA) of marine origin.Subjects and methods: Eighty-seven male volunteers from four public health center districts that were part of the Japan Public Health Center based Prospective Study (JPHC Study) cohort I, were included in this study. Habitual intake of fatty acid was obtained by 7 day weighed dietary records four times (in one area only twice) in 1994–1995. Blood was collected twice, in February and August of the same year, and the composition of FA in serum phospholipid was analyzed by gas chromatography. The correlation coefficient between serum phospholipid FA levels and fatty acid intake was calculated.Results: High correlations were observed for eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), which are marine origin n-3 PUFA (r=0.75, 0.49, 0.50, respectively). No significant correlation was observed for saturated fatty acid (SFA), although the monounsaturated fatty acid (MUFA), palmitoleic acid and oleic acid intake were moderately correlated (r=0.22, 0.35, respectively). The correlations for EPA, DPA and DHA were similar in both samples collected in February and August.Conclusions: These data suggest that in populations with a high and stable over time intake of n-3 PUFA of marine origin, a single measurement of serum phospholipids reflects the ranking of habitual intake of marine origin n-3 PUFA.European Journal of Clinical Nutrition (2001) 55, 643–650

Cruciferous Vegetables, Mushrooms, and Gastrointestinal Cancer Risks in a Multicenter, Hospital-Based Case-Control Study in Japan

We assessed the possible association of gastrointestinal cancers with cruciferous vegetables and mushrooms in a multicenter, hospital-based case-control study in an agricultural area of Japan. One hundred forty-nine cases and 287 controls for stomach cancer and 115 cases and 230 controls for colorectal cancer were matched by age, sex, and residential area. In stomach cancer, the protective effect of vegetables (consumption of total vegetable) was obscure, but it became clearer when we examined specific kinds of vegetables. Marginal associations were observed in the group of the highest consumption of Chinese cabbage (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.35-1.07), broccoli (OR = 0.60; 95% CI = 0.34-1.08), Hypsizigus marmoreus (Bunashimeji) (OR = 0.57; 95% CI =; 0.31-1.04) and Pholita nameko (Nameko) (OR = 0.56; 95% CI = 0.30-1.06). In colorectal cancer, we observed decreased risks from the highest tertile of total vegetables (OR = 0.22; 95% CI = 0.08-0.66) and low-carotene- containing vegetables (OR = 0.28; 95% CI = 0.08-0.77), and inverse associations were observed in the group of the highest consumption of broccoli (OR = 0.18; 95% CI = 0.06-0.58). Although the sample size was limited, subgroup analyses showed that the associations differed with the histopathological subtype. These findings suggest that cruciferous vegetables decrease the risk of both stomach and colorectal cancer, and that mushrooms are associated with a decreased risk of stomach cancer.

Folate, Vitamin B6, Vitamin B12, and Vitamin B2 Intake, Genetic Polymorphisms of Related Enzymes, and Risk of Colorectal Cancer in a Hospital-Based Case-Control Study in Japan

Abstract: We conducted a case-control study to investigate the association of nutrient intake involved in the one-carbon pathway of folate for DNA methylation and DNA synthesis and the related enzyme genetic polymorphisms with colorectal cancer. Cases were 107 patients newly diagnosed with colorectal cancer. Controls were 224 subjects matched with cases by sex, age, and residential area. Nutrient intake was assessed by a self-administered, semiquantitative food-frequency questionnaire. Four genetic polymorphisms—MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys—were determined using blood samples. Odds ratios were calculated using conditional logistic regression analysis adjusted for smoking, alcohol consumption, body mass index, and dietary fiber intake. Although folate intake was inversely associated with colorectal cancer, this association was attenuated after further controlling for dietary fiber intake. Neither vitamin B6, vitamin B12, nor vitamin B2, nor any genetic polymorphism was significantly associated with colorectal cancer. MTRR polymorphism interacted with the association of folate (P for interaction = 0.04) or vitamin (P for interaction = 0.02) with colorectal cancer, although the other polymorphisms did not interact with any nutrient intake. In conclusion, the study did not support the existing hypothesis of gene-nutrient interaction in colorectal carcinogenesis.

Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer.

The aim of the present study was to examine the association between daily omega-3 fatty acid intake and depression in Japanese cancer patients. Omega-3 fatty acid intake in 771 patients with newly diagnosed primary lung cancer was evaluated using a food-frequency questionnaire, and the prevalence of depression was examined using the cutoff values for the depression subscale included in the Hospital Anxiety and Depression Scale. After adjustment for potential confounding factors, the odds ratio (OR) for depression among patients in the highest quartile of the total eicosapentaenoic acid- (C20:5n-3) and docosapentaenoic acid (C22:6n-3)-intake group compared with patients in the lowest quartile was not significantly different. On the other hand, the OR among the highest quartile of α-linolenic acid (C18:3n-3) intake (adjusted OR=0.50, 95% CI: 0.31–0.71, P for trend=0.004) and the highest quartile of total omega-3 fatty acid intake (adjusted OR=0.55, 95% CI: 0.35–0.88, P for trend=0.022) were significantly different. These results suggest that total eicosapentaenoic acid and docosapentaenoic acid intake might not be associated with depression in Japanese patients with newly diagnosed lung cancer, but that α-linolenic acid intake and total omega-3 fatty acid intake might be.

Fish, Long-Chain n-3 Polyunsaturated Fatty Acids, and Risk of Colorectal Cancer in Middle-Aged Japanese: The JPHC Study

Abstract: Although long-chain n-3 polyunsaturated fatty acids (Ln-3 PUFA), which are abundant in fish, have shown protective effects on colorectal cancer in laboratory studies, epidemiological studies to date have not been consistent. We evaluated the relationship of consumption of fish and Ln-3 PUFA to the colon and rectal cancer risk in the two cohorts of the Japan Public Health Center-based prospective study of 42,525 men and 46,133 women. Dietary and other exposure data were obtained between 1990 and 1994. Through December 1999, 705 cases of colon and rectal cancer were documented. When data from the two cohorts were pooled, multivariable relative risks (RRs) for the highest quartile compared with the lowest quartile of fish consumption were 1.07 (95% confidence interval, CI = 0.77-1.48) for colon cancer and 0.95 (95% CI = 0.63-1.43) for rectal cancer with no dose-risk trend. RRs for the highest quartile compared with the lowest quartile of eicosapentaenoic acid consumption were 1.05 (95% CI = 0.76-1.46) for colon cancer and 0.91 (95% CI = 0.60-1.38) for rectal cancer with no dose-risk trend. This study does not support the role of fish and Ln-3 PUFA in the etiology of colon and rectal cancer in this population whose fish consumption was high and the variation in Ln-3 PUFA consumption was large.

Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan.

We investigated associations among intake of folate, vitamin B2, vitamin B6, vitamin B12, and polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes and breast cancer risk in a Japanese population. A hospital based, case-control study was conducted in Nagano Prefecture, Japan, in 388 pairs of patients with histologically confirmed invasive breast cancer and age- and area-matched controls selected from medical checkup examinees. Energy-adjusted intakes of folate and other B vitamins were derived from a validated food frequency questionnaire. Genotyping was completed for MTHFR (C677T and A1298T) and MTR (A2756G). Odds ratios and 95% confidence intervals were calculated by the conditional logistical regression model. Median dietary folate intake (μg/day) in the control group was 438.2 (interquartile range: 354.9–542.9). Neither dietary intake of folate, vitamin B2, vitamin B6, or vitamin B12 nor polymorphisms of MTHFR or MTR genes were significantly associated with breast cancer risk. Further, no significant interaction was found among nutrients, polymorphisms, and breast cancer risk. Associations of nutrients with breast cancer risk did not differ by hormone receptors status. We conclude that dietary intake of folate and related B vitamins and genotypes of MTHFR or MTR have no overall association with breast cancer risk in Japanese women.

hOGG1 Ser326Cys polymorphism, interaction with environmental exposures, and gastric cancer risk in Japanese populations

Oxidative DNA damage caused by reactive oxygen species (ROS) generated by Helicobacter pylori (H. pylori) infection or smoking may be a cause of gastric cancer development. 8‐Hydroxydeoxyguanine (8‐OHdG) formation is one of the most common types of oxidative DNA damage, while human oxoguanine glycosylase 1 (hOGGl) is responsible for repairing 8‐OHdG lesions. Among several hOGGl gene polymorphisms, the SerCys polymorphism at position 326 is related to biological function. To investigate the association between Ser326Cys hOGGl polymorphism and gastric cancer in relation to the potential risk factors of gastric cancer and antioxidant dietary or nutrient intakes, we conducted a case‐control study with 142 histologically‐confirmed gastric cancer cases and 271 age, sex‐matched healthy controls in Japanese populations. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGGl Ser/Cys or Cys/Cys genotype and atrophic gastritis (P for interaction =0.03). No significant interaction was found between hOGGl genotype and antioxidant dietary or nutrient intakes. The results of the present study suggest that patients with atrophic gastritis in conjunction with the hOGGl Cys allele might have a higher susceptibility to gastric cancer.

Impact of the revision of a nutrient database on the validity of a self-administered food frequency questionnaire (FFQ).

BACKGROUND Revision of the national nutrient database in 2000 had a strong impact on the absolute level of estimated nutrient intake in dietary assessments. However, whether it influenced the ranking of individuals by estimated intake, a more important function in epidemiologic studies, has not been investigated. Here, we investigated the effect of this revision of the nutrient database on the validity of a food frequency questionnaire (FFQ) used to estimate nutrient intake in the Japan Public Health Center-based prospective Study (JPHC Study). METHODS Subjects were a subsample of the JPHC Study who volunteered to participate in the validation study of the FFQ. Validity of the FFQ was evaluated by reference to the 28-day weighed dietary records as a gold standard. Nutrient intake according to the FFQ was recalculated using the revised database, and the results were compared to those using the previous database. Spearman’s rank correlation coefficients (CCs) between intakes estimated by the FFQ and dietary records were computed using the revised database, and were compared to CCs computed using the previous database. RESULTS For most of the nutrients, mean intake increased or decreased significantly using the revised database. However, no notable change was seen for the CC between estimated intake according to dietary records and FFQ when the revised database was used for calculation. Differences in the point estimates of the CCs ranged from -0.14 to 0.15. Likewise, CCs between biomarkers and estimated intake according to FFQ were similar for the two databases. CONCLUSION Despite changes in intake levels for many nutrients, the validity of our FFQ using rank correlation by nutrient intake was not influenced by revision of the nutrient database in Japan.