Toshiro Takezaki

A Large-scale, Hospital-based Case-Control Study of Risk Factors of Breast Cancer According to Menopausal Status

We conducted a large‐scale, hospital‐based case‐control study to evaluate differences and similarities in the risk factors of female breast cancer according to menopausal status. This study is based on a questionnaire survey on life style routinely obtained from outpatients who first visited the Aichi Cancer Center Hospital between January 1, 1988 and December 31, 1992. Among 36,944 outpatients, 1,186 women with breast cancer detected by histological examination were taken as the case group (607 premenopausal women and 445 postmenopausal women) and 23,163 women confirmed to be free of cancer were selected as the control group. New findings and reconfirmed factors of breast cancer were as follows. 1) The risk of at least one breast cancer history among subjects’ first‐degree relatives was relatively high among pre‐ as well as post‐menopausal women. 2) A protective effect of physical activity against breast cancer was observed among both pre‐ and post‐menopausal women. 3) Dietary control decreased the risk of premenopausal breast cancer. 4) Current smoking and drinking elevated the risk of breast cancer in premenopausal women. 5) Decreasing trends of breast cancer risk were associated with intake of bean curd, green‐yellow vegetables, potato or sweet potato, chicken and ham or sausage in premenopausal women, while in postmenopausal women a risk reduction was associated with a more frequent intake of boiled, broiled and/or raw fish (sashimi). Further study will be needed to clarify the age group‐ and/or birth cohort‐specific risk factors for breast cancer among the young generation in Japan.

Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan

Objectives: The purpose of this study was to examine the hypothesis that tea and coffee consumption have a protective effect against development of digestive tract cancers. Methods: A comparative case-referent study was conducted using Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) data from 1990 to 1995 in Nagoya, Japan. This study comprised 1,706 histologically diagnosed cases of digestive tract cancers (185 esophagus, 893 stomach, 362 colon, 266 rectum) and a total of 21,128 non-cancer outpatients aged 40 years and over. Logistic regression was used to analyze the data, adjusting for gender; age; year and season at hospital-visit; habitual smoking and alcohol drinking; regular physical exercise; fruit, rice, and beef intake; and beverage intake. Results: The odds ratio (OR) of stomach cancer decreased to 0.69 (95 percent confidence interval [CI] = 0.48-1.00) with high intake of green tea (seven cups or more per day). A decreased risk was also observed for rectal cancer with three cups or more daily intake of coffee (OR = 0.46, CI = 0.26-0.81). Conclusions: The results suggest the potential for protective effect against site-specific digestive tract cancer by consumption of green tea and coffee, although most associations are limited only to the upper category of intake and have no clear explanation for site-specificity.

Protective Effect of Allium Vegetables against Both Esophageal and Stomach Cancer: A Simultaneous Case‐referent Study of a High‐epidemic Area in Jiangsu Province, China

To study the relation between allium vegetable intake and cancer of the esophagus (EC) and stomach (SC) in Yangzhong city, which is one of the highest‐risk areas for these cancers in Jiangsu province, China, a simultaneous case‐referent study was conducted using histopathologically confirmed cases (EC: n=81, SC: n=153) and population‐based referents (n=234). A questionnaire was used to collect information on the general status of subjects, their dietary habits, frequency intake of allium vegetables and other foods, tea consumption, smoking and alcohol drinking. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by a multiple logistic regression model. The results showed that frequent intake of allium vegetables (including garlic, onion, Welsh onion and Chinese chives), raw vegetables, tomatoes and snap beans, and tea consumption were inversely associated with the risk for EC and SC. In the highest consumption category (≥1 time/ week) of garlic, onion, Welsh onion and Chinese chives, the adjusted ORs compared with the lowest category (<1 time/month) were 0.30 (CI=0.19−0.47), 0.25 (CI=0.11−0.54), 0.15 (CI=0.08−0.26), and 0.57 (CI=0.23−1.42) for EC, and 0.31 (CI=0.22−0.44), 0.17 (CI=0.08−0.36), 0.22 (CI=0.15−0.31) and 0.40 (CI = 0.17−0.94) for SC, respectively. The main results in the present study suggested that allium vegetables, like raw vegetables, may have an important protecting effect against not only stomach cancer, but also esophageal cancer.

Epidemiological features of first-visit outpatients in Japan: Comparison with general population and variation by sex, age, and season

To evaluate the methodological issues in using first-visit outpatients as controls in epidemiological studies, the features of general lifestyles of non-cancer outpatients at Aichi Cancer Center Hospital (ACCH) were compared with those of the general population, and their variation by sex, age, and season was determined by using a self-administered questionnaire. The study included 1231 subjects randomly selected from the Nagoya electoral roll (CRG), and three groups of non-cancer ACCH outpatients living in Nagoya; 800 from the period September to December 1992 (OPG1), 2326 from January to December 1992 (OPG2), and 12,243 from January 1991 to December 1992 (OPG3). In the younger age group, the proportion of current smokers was higher in the CRG than in the OPGs. In the older age groups, the proportion of those who consumed fresh vegetables and fruit everyday was higher in the OPGs than in the CRG. For other items, the features of the OPGs were not significantly different from those of the CRG. Among the OPG3, there were differences in the features of general lifestyles between sexes and consumption of several food items varied with age. Seasonal variation, however, was only observed in the specific food items where supply varied seasonally. It was concluded that, with due consideration of age, sex, and season in the analysis, it is feasible to use non-cancer outpatients as controls in epidemiological studies.

An Association Between Long-Term Exposure to Ambient Air Pollution and Mortality From Lung Cancer and Respiratory Diseases in Japan

Background Evidence for a link between long-term exposure to air pollution and lung cancer is limited to Western populations. In this prospective cohort study, we examined this association in a Japanese population. Methods The study comprised 63 520 participants living in 6 areas in 3 Japanese prefectures who were enrolled between 1983 and 1985. Exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5), sulfur dioxide (SO2), and nitrogen dioxide (NO2) was assessed using data from monitoring stations located in or nearby each area. The Cox proportional hazards model was used to calculate the hazard ratios associated with the average concentrations of these air pollutants. Results The 10-year average concentrations of PM2.5, SO2, and NO2 before recruitment (1974–1983) were 16.8 to 41.9 µg/m3, 2.4 to 19.0 ppb, and 1.2 to 33.7 ppb, respectively (inter-area range). During an average follow-up of 8.7 years, there were 6687 deaths, including 518 deaths from lung cancer. The hazard ratios for lung cancer mortality associated with a 10-unit increase in PM2.5 (µg/m3), SO2 (ppb), and NO2 (ppb) were 1.24 (95% confidence interval: 1.12–1.37), 1.26 (1.07–1.48), and 1.17 (1.10–1.26), respectively, after adjustment for tobacco smoking and other confounding factors. In addition, a significant increase in risk was observed for male smokers and female never smokers. Respiratory diseases, particularly pneumonia, were also significantly associated with all the air pollutants. Conclusions Long-term exposure to air pollution is associated with lung cancer and respiratory diseases in Japan.

Subsite-specific risk factors for colorectal cancer: a hospital-based case-control study in Japan.

To investigate the subsite-specific risk factors for colorectal cancer, we conducted a case-control study, using a common questionnaire which inquired about general lifestyles over the past five years (1988–92), at the Aichi Cancer Center Hospital, Nagoya, Japan. This study compared 432 patients with histopathologically diagnosed colorectal cancer (94 proximal colon [cecum, ascending colon, transverse colon]; 137 distal colon [descending colon, sigmoid colon]; 201 rectum [rectosigmoid, rectum]); and 31,782 first-visit outpatient controls who were free from cancer. In both genders, habitual smoking selectively increased the risk for rectum cancer. Soft or loose feces increased the risk for all subsites of colorectal cancer, particularly in female cancer (odds ratio [OR]=4.5). Among female dietary habits, Japanese-style foods decreased the risk factors for distal colon cancer, but increased the risk for proximal colon cancer. These results suggested that the risk factors for colorectal cancer differ by subsite among such a low-risk population as the Japanese. It is suggested also that ‘irritable bowel’ (soft or loose feces) might be associated with distal subsites of colorectal cancer, independently or combined with habitual smoking. Cancer Causes and Control 1995, 6, 14–22.

HOGG1 Ser326Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese

Oxidative stress is involved in many types of DNA damage, e.g., resulting in 8‐hydroxyguanine adducts. Since a human counterpart exists for the yeast gene OGG1 (hOGG1) encoding an enzyme that repairs 8‐hydroxyguanine, its polymorphism, Ser326Cys, might have potential as a genetic marker for cancer susceptibility. To investigate its association with stomach cancer risk and possible interactions with environmental factors, we conducted a case‐control study of 101 stomach cancer cases and 198 controls using PCR‐single‐strand conformation polymorphism and a questionnaire approach. The proportional distribution of the Cys/Cys alleles did not differ between stomach cancer cases and controls, but subgroup analyses revealed that a frequent drinking habit elevated the odds ratio (OR) for stomach cancer in Cys/Cys compared to Ser/Ser and Ser/Cys carriers. The ORs with frequent consumption of pickled vegetables and meat tended to be higher in Cys/Cys than in Ser/Ser and Ser/Cys carriers, these interactions being on the borderline of statistical significance. Our findings suggest that the hOGG1 Ser326Cys polymorphism may alter the impact of some environmental factors on stomach cancer development. For confirmation, an additional study with a larger number of subjects is now required.

Glutathione-S-transferases M1 (GSTM1) and GSTT1 genotype, smoking, consumption of alcohol and tea and risk of esophageal and stomach cancers: a case-control study of a high-incidence area in Jiangsu Province, China

To evaluate interactions between lifestyle factors and glutathione-S-transferases M1 (GSTM1) and GSTT1 genotypes with reference to development of esophageal and stomach cancers, we conducted a case-control study of 141 cases of esophageal cancer, 153 cases of stomach cancer and 223 population-based controls in Huaian City of Jiangsu Province, China. GSTM1 and GSTT1 genotypes were identified by multiplex polymerase chain reaction. The GSTM1 null genotype was associated with an increased odds ratio for esophageal cancer (2.17, 95% confidence interval=1.35-3.50), but not for stomach cancer. A combined effect was also observed between smoking and the GSTM1 null genotype with regard to esophageal risk. Tea drinking was a protective factor for both cancers, its effect being independent of the GSTT1 and GSTM1 genotypes. These findings suggest the GSTM1 polymorphism is involved in the susceptibility to esophageal cancer development, and tea consumption reduces the risk of esophageal and stomach cancers.

Smoking and Lung Cancer Risk in American and Japanese Men: An International Case-Control Study

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Subsite (cervix/endometrium)-specific risk and protective factors in uterus cancer

In Japan the incidence of cervical cancer has been high, but has recently been decreasing gradually, while the incidence of endometrial cancer is running at lower levels but is gradually increasing. To clarify the common and/or specific risk and/or protective factors of cervical cancer (CC) in contrast with endometrial cancer (EC), a comparative case‐control study was conducted at the Aichi Cancer Center Hospital, Japan. In total, 556 CC cases and 145 EC cases were included and 26,751 women, confirmed as free of cancer, were chosen as the common control group. Odds ratio and its 95% confidence interval (95%CI) for each exposure variable were estimated by using an unconditional logistic regression model adjusted for age and first‐visit year. Habitual smoking and experience of pregnancy increased the risk of CC, while decreasing the risk of EC. Greater body mass index (>20), daily intake of fruit and more frequent intake of boiled or broiled fish (>1–2 times/week) decreased the risk of CC, whereas they increased the risk of EC. Daily intake of milk decreased the risk of CC. The results obtained from this study suggest that several EC‐increasing risk factors are in fact CC‐decreasing determinants. The observed risk reduction in both CC and EC by physical exercise and dietary control for health is noteworthy from the public health standpoint and warrants further investigation.