Norihiko Hayakawa

Prospective study of screening for stomach cancer in Japan

Although screening for stomach cancer is a widespread community service in Japan, the benefits of the screening program remain unclear. Our study investigated prospectively the relation between participation in stomach‐cancer screening during the past 12 months and subsequent deaths. Data was derived from the Japan Collaborative Cohort Study, in which 480 stomach‐cancer deaths were identified during an 8‐year follow‐up period. Cox proportional hazard regression was used to estimate the relative risk of death from stomach cancer and that from other causes while adjusting for potential confounding factors. In men, screening participation was associated significantly with a reduced risk of death from stomach cancer (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.41–0.70). The extent of the risk reduction was greater than potential health selection (for deaths other than stomach, RR = 0.71). The adjustment for potential confounding variables, however, attenuated the difference in risk of death (stomach cancer, RR = 0.65; other causes, RR = 0.71). In women, the magnitude of the association between screening participation and death from stomach cancer (RR = 0.74; 95% CI = 0.52–1.07) was equal to that for deaths from non‐stomach cancers (RR = 0.74). Subgroup analysis showed that women with a parental history of stomach cancer had a reduced risk of death from stomach cancer associated with screening (RR = 0.32; 95% CI = 0.12–0.87). The present results underline the potential for selection bias in observational studies, and thus it remains an open question whether screening for stomach cancer is effective.

Leptin Is Associated with an Increased Female Colorectal Cancer Risk: A Nested Case-Control Study in Japan

Objective: To elucidate whether leptin is involved in the etiology of female colorectal cancer. Methods: A case-control study nested in the Japan Collaborative Cohort Study. We compared serum leptin levels in 58 cases of female colorectal cancer with those in 145 controls matched for study area and age. Data were analyzed using a conditional logistic regression model with adjustments for known risk factors for the development of colorectal cancer. Quintile cutoff points were determined on the distribution of leptin levels in cases and controls combined. Results: Serum geometric mean levels of leptin were 6.88 ng/ml in cases and 6.00 ng/ml in controls. The odds ratios of female colorectal cancer risk were 1.40 (95% confidence interval, CI: 0.41–4.78) for the category of the second and third quintiles combined, and 4.84 (CI: 1.29–18.1) for the category of the fourth and fifth quintiles combined relative to the first quintile after adjustment for body mass index (BMI), life-style factors, reproductive factors, and hormonal variables including insulin-like growth factor and its binding protein. Conclusion: Our results suggest that leptin most likely increases the risk of female colorectal cancer substantially independent of BMI.

Diet and Colorectal Cancer Mortality: Results From the Japan Collaborative Cohort Study

Abstract: The relationship between diet and colorectal cancer mortality was analyzed in a prospective study of 45,181 men and 62,643 women aged 40-79 yr enrolled in the Japan Collaborative Cohort Study. Between 1988 and 1990, subjects completed a self-administered questionnaire on their sociodemographic characteristics, diet, and other lifestyle habits. During the follow-up period (average 9.9 yr), 284 colon cancer deaths (138 men and 146 women) and 173 rectal cancer deaths (116 men and 57 women) were confirmed. The only significant association of colorectal cancer mortality with vegetable intake was observed between male rectal cancer mortality and green leafy vegetable consumption [hazard ratio (HR) using Cox proportional hazard models = 0.6; 95% confidence interval (CI) = 0.3-0.9; P for trend = 0.02]. Yogurt intake was also inversely associated with male rectal cancer mortality (HR = 0.5; 95% CI = 0.2-1.0; P for trend = 0.04). Egg consumption was positively associated with male colon cancer mortality (P for trend = 0.04). Women with high fruit consumption had increased colon cancer mortality (HR = 1.6; 95% CI = 1.0-2.6; P for trend = 0.04). It should be noted that this study lacked statistical power due to small sample size and measurement error in the food-frequency questionnaire. Further investigation is therefore necessary to confirm the association between diet and colorectal cancer, especially by subsites and gender.

A prospective study of stomach cancer death in relation to green tea consumption in Japan

To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 30 370 men and 42 481 women aged 40–79. After adjustment for age, smoking status, history of peptic ulcer, family history of stomach cancer along with certain dietary items, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.6 (95% CI: 0.9–2.9), 1.1 (95% CI: 0.6–1.9), 1.0 (95% CI: 0.5–2.0), and 1.0 (95% CI: 0.5–2.0), respectively, in men (P for trend=0.669), and 1.1 (95% CI: 0.5–2.5), 1.0 (95% CI: 0.5–2.5), 0.8 (95% CI: 0.4–1.6), and 0.8 (95% CI: 0.3–2.1), respectively, in women (P for trend=0.488). We found no inverse association between green tea consumption and the risk of stomach cancer death.

A prospective study of body size and colon cancer mortality in Japan: The JACC Study

OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese.DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43 171 men and 58 775 women aged 40–79 y who respond to a questionnaire on current weight and height, weight around 20 y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and 20-BMI, respectively) were calculated.RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424 698 person-years among men and 122 deaths during the follow-up of 591 787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI ≥28 kg/m2 had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44–8.06) compared with those with BMI of 20–<22 kg/m2. 20-BMI also presented the same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26 kg/m2, that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29–9.02) compared with those with 20-BMI of <22 and B-BMI of <22 kg/m2. There were no corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among men.CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.

A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose

Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the hombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor—age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births—conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early agefollowing exposure may be protective against radiation-related risk.

Dietary Fiber and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study

To examine the association of dietary fiber with the risk of colorectal cancer in a population with a high incidence of cancer and a low fiber intake, we analyzed the data from the Japan Collaborative Cohort Study. From 1988 to 1990, 43,115 men and women aged 40 to 79 years completed a questionnaire on dietary and other factors. Intake of dietary fiber was estimated using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 443 colorectal cancer cases were recorded. In all participants, we found a decreasing trend in risk of colorectal cancer with increasing intake of total dietary fiber; the multivariate-adjusted RRs across quartiles were 1.00, 0.96 [95% confidence interval (95% CI), 0.72-1.27], 0.72 (0.53-0.99), and 0.73 (0.51-1.03; Ptrend = 0.028). This trend was exclusively detected for colon cancer: the corresponding RRs were 1.00, 0.90 (95% CI, 0.64-1.26), 0.56 (0.38-0.83), and 0.58 (0.38-0.88; Ptrend = 0.002). The decrease in RRs with increasing intake of dietary fiber was larger in men than in women. No material differences appeared in the strength of associations with the risk between water-soluble and insoluble dietary fiber. For food sources of fiber, bean fiber intake was somewhat inversely correlated with colorectal cancer risk. This prospective study supported potential protective effects of dietary fiber against colorectal cancer, mainly against colon cancer. The role of dietary fiber in the prevention of colorectal cancer seems to remain inconsistent, and further investigations in various populations are warranted. (Cancer Epidemiol Biomarkers Prev 2007;16(4):668–75)

Family history and the risk of stomach cancer death in Japan: Differences by age and gender

Familial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow‐up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first‐degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11–2.31) and women (RR 2.47; 95% CI 1.50–4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40–59 (RR 2.62; 95% CI 1.34–5.11 for men and RR 5.88; 95% CI 2.70–12.82 for women) than in the age group from 60–79 (RR 1.31; 95% CI 0.84–2.05 for men and RR 1.44; 95% CI 0.72–2.88 for women). In the age group from 40–59, men with fathers history and women with mothers and sisters history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51–6.55, RR 10.46; 95% CI 4.54–24.12, RR 13.39; 95% CI 3.89–46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46–20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender‐influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility.

A case-control interview study of breast cancer among Japanese A-bomb survivors. I. Main effects

Women with breast cancer (cases=196) and without the disease (controls=566), selected from the Life Span Study sample of A-bomb survivors and nonexposed residents of Hiroshima and Nagasaki, Japan, and matched on age at the time of the bombings, city, and estimated radiation dose, were interviewed about reproductive and medical history. A primary purpose of the study was to identify strong breast cancer risk factors that could be investigated further for possible interactions with radiation dose. As expected, age at first full-term pregnancy was strongly and positively related to risk. Inverse associations were observed with number of births and total, cumulative period of breast feeding, even after adjustment for age at first full-term pregnancy. Histories of treatment for dysmenorrhea and for uterine or ovarian surgery were associated positively and significantly with risk at ages 55 or older, a finding that requires additional study. Other factors related to risk at older ages were the Quetelet index (weight [kg]/height [cm]2) at age 50, history of thyroid disease, and hypertension. Neither age at menarche nor age at menopause was associated significantly with risk. Subjects appeared to be poorly informed about history of breast cancer or other cancer in themselves or in their close relatives; this finding suggests that innovative strategies may be required when studying familial cancer patterns in Japanese populations.

A nested case–control study of stomach cancer in relation to green tea consumption in Japan

To evaluate whether green tea consumption provides protection against stomach cancer, the relative risks (RRs) were calculated in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 157 incident cases and 285 controls aged 40–79 years. Cox proportional hazards regression analysis was used to estimate the RRs for stomach cancer. It was found that green tea consumption had no protective effect against stomach cancer. After adjustment for age, smoking status, H. pylori infection, history of peptic ulcer, and family history of stomach cancer along with certain dietary elements, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.3 (95% confidence interval (CI): 0.6–2.8), 1.0 (95% CI: 0.5–1.9), 0.8 (95% CI: 0.4–1.6), and 1.2 (95% CI: 0.6–2.5), respectively (P for trend=0.899). We found no inverse association between green tea consumption and the risk of stomach cancer.