Leprosy and cancer: a retrospective cohort study in Hawaii.

We used data collected on a retrospective cohort of 1,123 leprosy patients living in Hawaii between 1940 and 1970, to test the hypotheses that patients with lepromatous leprosy, who have an impairment in their cellular immune response, would have an increased risk for cancer and that patients with tuberculoid leprosy, who are immunologically competent, would have a normal or even a reduced cancer risk from beneficial stimulation of their cellular immune system by exposure to the Mycobacterium leprae organisms. Based on the survival analysis method, the results of the study supported the predicted increase in cancer cases among the lepromatous leprosy patients (19 observed, 12.7 expected; risk ratio = 1.5) and the predicted decrease among the tuberculoid leprosy patients (14 observed, 17.8 expected; risk ratio = 0.8); in both groups, the findings were consistent across the five racial categories of the study. However, none of these differences between observed and expected cases was statistically significant at the 5% level. The study provided no support for the alternate hypothesis that chronic antigenic stimulation by the M. leprae organisms might lead to an increase in tumors of the lymphoreticular system.

Hepatitis C virus infection and risk of hepatocellular carcinoma among Japanese: possible role of type 1b (II) infection.

BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important risk factor for hepatocellular carcinoma HCC), the strength of this association has been inconsistent. In addition, the role of specific HCV genotypes in HCC progression has not yet been determined. PURPOSE: We conducted a case-control study to estimate the relative risk (RR) of HCC in relation to HCV infection among residents of the Fukuoka Prefecture, where HCC risk is among the highest in Japan, and to examine whether the risk differs according to HCV genotypes and/or HCV RNA titers. METHODS: Stored serum samples obtained from 91 patients with HCC and 410 healthy control subjects, who had been frequency matched to the patients with regard to sex and age, were tested for antibodies to HCV by use of second-generation immunoradiometric and immunoblot assays. The presence of serum HCV RNA and of specific HCV genotypes was determined by use of polymerase chain reaction-based assays, and HCV RNA titers were measured by use of a branched DNA assay. RESULTS: Antibodies to HCV were detected in 71 patients (78.0%) and in 30 control subjects (7.3%), of whom 57 patients and 25 control subjects had serum HCV RNA. One patient was positive for HCV RNA but not for antibodies to HCV. The sex- and age-adjusted RR of HCC among individuals positive for antibodies to HCV was estimated to be 53.7 (95% confidence interval [CI] = 27.1-106.2). Antibodies to HCV were much more prevalent among patients negative for serum, hepatitis B surface antigen (HBsAg) (69 of 72, 95.8 %) than among HBsAg-positive patients (two of 19, 10.5%); the RR increased to 339.6 (95% CI = 96.5-1195.8) in the separate analysis of HBsAg-negative subjects. The most frequent genotype among HCV RNA-positive subjects was type lb (also called type II) (found in 49 [86.0%] of 57 patients and in 15 [60.0%] of 25 control subjects); individuals with type 1b infection experienced a significantly elevated risk (RR = 3.8; 95% CI = 1.0-13.9) compared with the risk observed for individuals with type 2a (also called type III) infection. No statistically significant association between HCV RNA titers and HCC was evident. CONCLUSIONS: HCV infection, particularly type 1b infection, plays an important role in the development of HCC among the study population. We estimated that approximately 78% (95% CI = 69%-86%) of the HCCs that occur in this high-risk area are attributable to HCV infection, if we assume that the patients in this study were representative population samples. IMPLICATIONS: Further studies are needed to clarify potential risk factors, including specific HCV genotypes, for progression to HCC among HCV carriers.

Combined treatments with vitamin A and 5-fluorouracil and the growth of allotransplantable and syngeneic tumors in mice.

The combined effect of retinol palmitate (RP) and 5-fluorouracil (FUra) was examined with the use of allotransplantable and syngeneic murine tumor systems. The ip combined administration of RP (5,000 IU/kg/day) and FUra (5 mg/kg/day, 20 mg/kg/day, or 20 mg/kg/every 3d day) suppressed the tumor growth in ICR/JCL mice given sc inoculations of 5 X 10(6) allotransplantable sarcoma 180 cells and prolonged the survival time of mice inoculated ip with 10(7) tumor cells, as compared with the survival time of mice given the single administration of either RP or FUra. Similar results were obtained when BALB/c mice were inoculated sc with a syngeneic BALB/c Meth A fibrosarcoma and treated with RP (5,000 IU/kg/day) and FUra (20 mg/kg/every 3d day). The growth of Meth A implanted on day 10, as a rechallenge, was significantly suppressed in the group pretreated with RP alone or both RP and FUra for 9 days from day 1. The growth of Meth 1, another syngeneic tumor of BALB/c origin, inoculated on day 10 as a rechallenge tumor was unaffected by the treatment with RP and/or FUra. An immune response to tumor-specific antigens seemed to be involved in the combined effects of these two drugs.

Augmentation of tumor immunity against syngeneic tumors in mice by beta-carotene.

The effect of beta-carotene on tumor immunity was examined with the use of a syngeneic murine tumor system. Oral administration of beta-carotene (120 micrograms/mouse/day) for 9 days from day 1 to the BALB/c mice inoculated sc with 10(7) syngeneic BALB/c Meth A fibrosarcoma cells (Meth A) led to a remarkable rejection against rechallenged Meth A implanted sc on day 10. The growth of Meth 1 fibrosarcoma (Meth 1), another syngeneic tumor of BALB/c origin, as a rechallenge tumor was unaffected by treatment with beta-carotene, thereby suggesting that beta-carotene may augment tumor rejection specific to tumor-specific antigens. Winn assay revealed that the suppressive effect on tumor growth of immune lymph node cells obtained from Meth A-inoculated beta-carotene-treated mice on day 12 was enhanced dose dependently. Primary effector cells responsible for the augmented rejection are Thy-1-positive, Lyt-1-negative, and Lyt-2-positive lymphocytes, presumably cytotoxic T-lymphocytes.

Cancer mortality in a cohort of naval shipyard workers in Hawaii: early findings.

A retrospective cohort study was performed in Hawaii among 4,779 male shipyard workers exposed to asbestos and 2,757 similar male workers without known asbestos exposure. Observed deaths from cancer and other causes in the 2 groups were compared with expected deaths on the basis of the general population of Hawaii by the use of a modified life-table method of analysis. A risk ratio for lung cancer of 1.7 was found for the exposed group after 20 or more years of follow-up. No increased risk for lung cancer was seen in the nonexposed group. These findings could not be attributed to differences in smoking habits in the 2 shipyard groups or between the shipyard groups and the general population. Because the maximum duration of follow-up for this analysis was 24 years, greater risks for lung cancer may be seen in the exposed group when the follow-up period is extended.

An epidemiologic study on the association between diet and breast cancer.

A case-control study of breast cancer was conducted in Hawaii with Japanese and Caucasian women between ages 45 and 74. Each case was matched to one hospital and one neighborhood control. In all, 183 sets of Japanese and 161 sets of Caucasian subjects were interviewed. No statistically significant differences were found between cases and controls in their mean intake of total fat, saturated fat, oleic acid, linoleic acid, animal protein, and cholesterol. Although there was a suggestion that cases consumed more saturated fat and oleic acid than neighborhood controls, the differences were not impressive. Consistent with other case-control studies, the present investigation did not provide strong support for the hypothesis that a high-fat diet is a risk factor for breast cancer. Further work is suggested to clarify the role of diet in determining breast cancer risk.

Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies.

We conducted a combined analysis of the original data to evaluate the consistency of 12 case-control studies of diet and breast cancer. Our analysis shows a consistent, statistically significant, positive association between breast cancer risk and saturated fat intake in postmenopausal women (relative risk for highest vs. lowest quintile, 1.46; P less than .0001). A consistent protective effect for a number of markers of fruit and vegetable intake was demonstrated; vitamin C intake had the most consistent and statistically significant inverse association with breast cancer risk (relative risk for highest vs. lowest quintile, 0.69; P less than .0001). If these dietary associations represent causality, the attributable risk (i.e., the percentage of breast cancers that might be prevented by dietary modification) in the North American population is estimated to be 24% for postmenopausal women and 16% for premenopausal women.

Serum testosterone:estradiol ratio and the development of hepatocellular carcinoma among male cirrhotic patients.

The reason for the large male predominance in the occurrence of hepatocellular carcinoma (HCC) remains unknown, and sex hormones may contribute to this phenomenon. We examined possible associations of serum levels of testosterone, free testosterone, estradiol, sex hormone binding globulin, and testosterone:estradiol ratio (T:E2 ratio) with HCC development in a follow-up study of 46 Japanese male patients with liver cirrhosis predominantly of hepatitis C virus origin (76%). Serum samples were collected between December 1985 and December 1987, and the patients were completely followed until the end of 1995 for an average of 5.1 years. During the follow-up period, 20 patients (43%) developed HCC. Univariate analysis demonstrated that serum T:E2 ratio and testosterone were significant predictors of HCC; the hazard ratios (and 95% confidence intervals) in the middle and upper tertiles relative to the lower tertile were 2.0 (0.5-7.6) and 4.0 (1.1-14.6; P trend = 0.03) for T:E2 ratio and 0.8 (0.2-3.1) and 2.9 (1.0-8.5; P trend = 0.05) for testosterone. Adjustment for age, serum albumin, hepatitis virus markers, and other clinicobiological variables substantially increased the corresponding hazard ratios. In multivariate analysis, serum free testosterone appeared to be associated with increased risk, yet independent associations with estradiol and sex hormone binding globulin were not evident. These results indicate that elevated serum testosterone, together with decreased serum estrogens, may promote the development of HCC in cirrhosis.

Cancer occurrence in shipyard workers exposed to asbestos in Hawaii.

Because large numbers of persons were employed in United States shipyards during World War II, the long-term risks for cancer associated with asbestos exposure in this setting are of great concern. We report here on the mortality findings after up to 29 years of follow-up on a retrospective cohort of 7971 male Pearl Harbor Naval Shipyard workers, which included more than 3000 men whose employment period spanned the World War II years. Compared with the general population of Hawaii, workers in the shipyard cohort had no increase in total mortality or in total cancer mortality irrespective of the duration of their exposure. However, the risk ratio for lung cancer among workers with at least 15 years of asbestos exposure was 1.4 overall (95% confidence interval, 1.0 to 2.0) and 1.7 for those with a latency interval of 30 or more years (95% confidence interval, 1.0 to 2.5). In addition, seven mesotheliomas occurred between 1977 and 1982 in a subset of the cohort, consisting of 7029 Hawaii residents who are being followed prospectively for cancer incidence. This represented an incidence of 67.3 per million men per year, compared with a rate of 5.8 for the state as a whole. These results suggest that the long-term relative increase in risk for mesothelioma may be even greater than that for bronchogenic carcinoma in this and other cohorts of United States shipyard workers exposed to asbestos.

Role of diet in cancer incidence in Hawaii.

Incidence rates for many sites of cancer show wide variations among the main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos, and Hawaiians). Major shifts in cancer rates among migrants to the islands suggest that environmental factors are at least in part responsible for these variations. One prominent area of difference among these ethnic populations is their diets, which can vary substantially, not only in the consumption of particular food items but also in mean nutrient intakes. In aggregate correlational analyses based on data from representative samples of these ethnic groups and corresponding population-based cancer incidence rates, we found significant associations between ethnic-sex-specific intakes of dietary fat (including total fat, as well as animal, saturated, and unsaturated fats) and breast, endometrial, and prostate cancers. Animal protein intake showed associations similar to those for dietary fat, but these two nutrients were highly correlated in the data. Cholesterol intake showed significant correlations with lung and laryngeal cancers. Analyses of both nutrient and food item data suggested an association of stomach cancer incidence with the consumption of fish products, particularly dried/salted fish, and with a lower intake of vitamin C. Preliminary findings from ongoing case-control studies showed the following relationships: an inverse association between lung cancer risk and the intake of food sources of vitamin A, especially foods containing carotenes; an inverse association between cancers of the lower urinary tract and vitamin A consumption, especially from supplements; a positive association between prostate cancer risk and dietary fat intake in men above age 69, but not in younger men; and a positive association between breast cancer risk and the intake of dietary fat (particularly saturated fat) and animal protein in postmenopausal women, especially the Japanese. Two large cohorts (50,000 and 5,000 subjects) on whom dietary information was collected between 1975 and 1980 are being followed prospectively for their occurrence of cancer.

Hepatitis C and hepatitis B in the etiology of hepatocellular carcinoma in the Japanese population.

We conducted case-control studies of hepatocellular carcinoma (HCC) and liver cirrhosis (LC) in relation to hepatitis C virus (HCV) and hepatitis B virus infection, involving 91 patients with HCC, 75 patients with LC who had no evidence of HCC, and 410 control subjects from the Japanese population. Serum antibody to HCV (anti-HCV) was detected by both enzyme-linked immunosorbent assay and recombinant immunoblot assay in 51, 51, and 3% of HCC, LC, and controls, respectively, whereas the corresponding prevalence of serum hepatitis B surface antigen (HBsAg) was 21, 11, and 2%, respectively. The relative risks (and 95% confidence intervals) for the presence of serum anti-HCV were estimated as 52.3 (23.9-114.3) for HCC and 64.4 (27.4-151.4) for LC. These values exceeded the relative risk of HCC (15.3) and that of LC (6.1) for positive serum HBsAg. Among male patients with HCC or LC, anti-HCV rates were very high in blood recipients (about 70%), heavy drinkers (46-62%), and those who had no identifiable risk factors (65-75%), indicating possible transmission of HCV via routes other than transfusion. No significant difference in anti-HCV status was observed between the HCC and LC groups. It was notable that anti-HCV was much less prevalent among HBsAg-positive patients with HCC or LC than among HBsAg-negative ones. There was a slight to moderate increase in HCC or LC risk among blood recipients and heavy drinkers after adjustment for anti-HCV status. These results indicate that, in Japan, the possible role of HCV infection in the etiology of HCC and LC is extremely large and seems to be more important than chronic hepatitis B virus infection.

The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population.

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methylcholanthrene-induced/non-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C [geometric mean and 95% confidence interval (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significantly higher than those of the other two genotypes (P = 0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype Val/Val (0.121 and 0.082-0.178 pmol/min/10(6) cells) in isoleucine-valine (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.042 and 0.034-0.052 pmol/min/10(6) cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/10(6) cells) (P < 0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < < or = 3.0: OR and 95 %CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AHH inducibility may strongly associate with the susceptibility to lung carcinogenesis.

Reproducibility of a diet history questionnaire in a case-control study of breast cancer.

The reproducibility of a diet history questionnaire was assessed as part of a case-control breast cancer study in Caucasian and Japanese women in Hawaii. The method was designed to estimate the intakes of total and saturated fat, cholesterol, and animal protein during a usual week before symptoms or diagnosis of disease in cases, and during a usual recent week in controls. Except for the time period of reference, the dietary technique was identical for all cases and controls. A subsample of 61 Japanese women (19 cases and 42 controls) and 56 Caucasian women (23 cases and 33 controls) participated in the dietary reinterview conducted within 3 months of the first interview. The mean difference in intake between the two interviews was small and not statistically significant (p greater than 0.05) for all four nutrient items among Japanese cases and controls and Caucasian cases, whereas the mean difference for all four nutrients was substantial and statistically significant (p less than 0.05) among the Caucasian controls. The intraclass correlation and the product-moment correlation were moderately high for all four nutrient items among Japanese cases and controls and Caucasian cases, but not among Caucasian controls. These findings indicate that the diet history method is reasonably reproducible in three of the four groups of studied subjects. Possible reasons for the poor reproducibility among Caucasian controls are discussed.

Association of diet and place of birth with stomach cancer incidence in Hawaii Japanese and Caucasians.

Stomach cancer incidence rates were compared among four groups: Japanese in Japan, Japanese in Hawaii, Caucasians in Hawaii, and all American whites. The highest rates at all ages occurred in the Japan Japanese, followed next by the Hawaii Japanese. Hawaii Caucasians tended to have similar age-specific rates to American whites in general. When the Japanese and Caucasians in Hawaii were divided by place of birth, the Japanese migrants to Hawaii had higher age-adjusted incidence rates than the Japanese born in Hawaii, while the Caucasian migrants to Hawaii (chiefly from the United States mainland) had lower rates than the Caucasians born in Hawaii. Examination of dietary data in relation to the place-of-birth-specific incidence rates showed positive association of stomach cancer with consumption of rice, pickled vegetables, and dried/salted fish, and a negative association with vitamin C intake. The results are consistent with the particular hypothesis that stomach cancer is caused by endogenous nitrosamine formation from dietary precursors, and that vitamin C may protect against the disease.

Serum lipids and gallstone disease. A study of self-defense officials in Japan.

Based on screening ultrasonography of the gallbladder in 2756 men who received a retirement health examination at the Self-Defense Forces Fukuoka Hospital, Japan, during the period of 1986 to 1990, we compared serum lipid levels among 61 men with gallstones, 38 who had the gallbladder removed previously, and 2494 with a normal gallbladder. In univariate analysis, men having gallstones and those who had had a cholecystectomy had lower concentrations of total and low-density-lipoprotein (LDL) cholesterol than did control subjects, although the differences were not statistically significant. After adjustment for body mass index, smoking, alcohol use, and glucose tolerance, inverse associations of cholecystectomy with total and LDL cholesterol levels were more pronounced and statistically significant. There was no appreciable difference in high-density-lipoprotein (HDL) cholesterol and triglycerides between control subjects and men either with gallstones or after cholecystectomy. The present study did not support a positive relation between gallstones and serum triglyceride levels and an inverse one to HDL cholesterol, which have been reported elsewhere. The findings on total and LDL cholesterol are consistent with some, but not all recent studies.

Population registries and other record resources for epidemiologic cancer research in the United States and Japan.

On the basis of the author's experience in epidemiologic studies on cancer in both the United States and Japan for the last 15 years, advantages and disadvantages of various record systems that can be utilized for epidemiologic cancer studies in these two countries are compared. Both countries are equally well provided with vital statistics and census records. Descriptive studies can be conducted without difficulties in both countries. For analytic studies, the Koseki record or family registration system in Japan provides an excellent tool in tracing subjects. However, Japanese record systems have problems as to management of hospital records, preservation of death certificates, etc. On the whole, restrospective cohort studies, particularly studies on patients, are more difficult in Japan than in the United States. There appear to be no material differences between these two countires as to case-control studies.

Reproducibility of dietary and other data from a self-administered questionnaire.

This study examined the reproducibility of information obtained from a questionnaire covering dietary and other information by comparing the answers to the questionnaires with answers to the same questions one year later. Answers from 191 men and 220 women, aged 40 to 65, in Fukuoka prefecture, Japan were compared. The surveys were conducted in November 1989 and November 1990. In the second survey, 97.2% of the first respondents answered. The concordance between the two responses was high, and the differences between the mean intakes from the two surveys were within 5% for 7 food items and within 15% for 14 food items among the 20 items about which the respondents were asked. The intraclass correlation coefficients varied from 0.30 for eggs to 0.62 for milk, with 16 items greater than 0.4. The differences in reproducibility between the sexes and two age categories were not significant. Close values also were obtained for the estimated consumption of salt. A substantially high reproducibility was observed on items regarding drinking and smoking; most of the kappa statistics and the intraclass correlation coefficients were between 0.5 and 0.9. The above reproducibility on individual food items was comparable to or better than those reported from other studies. The results of the present study thus indicate that the self-administered semiquantitative food intake questionnaire used for our cross-sectional study is useful for epidemiologic studies to assess the association between diet and various diseases. In particular, the present questionnaire is highly dependable regarding the overall group intake of foods.(ABSTRACT TRUNCATED AT 250 WORDS)

Ulcerative colitis and colorectal cancer: a follow-up study in Fukuoka, Japan.

BACKGROUND: Our goal was to study the higher death rate and the causes of such deaths among ulcerative colitis (UC) patients in the Japanese population, and to compare our findings in such cases with those for Crohn's disease (CD). METHODS: In all, 174 UC (male/female: 54/120) and 66 CD (34/32) patients who were registered for the research promotion programme in Fukuoka prefecture (1971-1981) were traced up to the end of 1994. The standardized mortality ratios (SMR) were calculated based on the death rates of the Japanese population by age, sex and calendar year. RESULTS: The overall follow-up rate was 96.7%. Among the UC patients, the SMR for all causes were 0.84 (95% CI: 0.11-4.31) for men; 1.05 (95% CI: 0.08-4.69) for women; and 0.94 (95% CI :0.09-4.50) for both sexes combined. When excluding deaths due to colorectal cancer, the SMR for the same groups were 0.43, 0.94 and 0.67, respectively. The SMR for both sexes were 1.82 (95% CI: 0.17-5.96) for malignant neoplasms and 9.93 (95% CI: 4.67-17.3) for colorectal cancer. Patients who died from colorectal cancer showed onset at a younger age (mean: 25.5 years) as well as a longer disease course of UC (mean: 17.0 years). Regarding the CD patients, the SMR for all causes were 1.75 (95% CI: 0.15-5.75) for both sexes. Most deaths were caused by gastrointestinal complications. CONCLUSIONS: An excess mortality from colorectal cancers was indicated in the UC patients, especially in males. The overall SMR in male UC patients decreased by 50% when the deaths from colorectal cancer were excluded. The excess mortality in those with CD over UC patients was attributed to gastrointestinal complications rather than malignant diseases. Some carcinogenic factors therefore seem most likely to exist in the pathogenesis of UC.

Relationship of alcohol use, physical activity and dietary habits with serum carotenoids, retinol and alpha-tocopherol among male Japanese smokers.

BACKGROUND: Despite considerable interest in the anticarcinogenic and anti-atherosclerotic effects of carotenoids and alpha-tocopherol, little is known about determinants of these serum micronutrients. METHODS: The association of lifestyle factors including alcohol use, physical activity and dietary habits with serum levels of carotenoids (lycopene, lutein, cryptoxanthin and beta-carotene), retinol and alpha-tocopherol were studied in 194 healthy men aged 24-60 years who smoked > 15 cigarettes/day. A self-administered questionnaire ascertained consumption frequency of 12 food items, alcohol consumption, levels of physical activity and the number of cigarettes smoked per day. RESULTS: Of the dietary items studied, total vegetable intake was significantly, positively associated with beta-carotene levels, as was fruit intake with serum levels of each carotenoid. Tofu intake was unexpectedly, but strongly related to decreased levels of cryptoxanthin and beta-carotene. None of the food items was materially related to serum levels of retinol and alpha-tocopherol. Alcohol consumption was most strongly and inversely associated with levels of all the carotenoids except lutein, whereas was positively associated with retinol level but not with alpha-tocopherol level. Frequency of participation in sports was significantly and positively associated with both retinol and alpha-tocopherol levels. The amount of cigarettes smoked per day was unrelated to each micronutrient level in this study of moderate or heavy smokers. CONCLUSIONS: The consumption of vegetables and fruits is an important determinant of serum carotenoid levels even in smokers. Alcohol consumption is inversely associated with carotenoid levels, although the mechanism for this is not clear. Tofu and physical activity influence serum levels of antioxidative micronutrients, and these relationships need further studies.

Various factors associated with the manifestation of influenza-like illness.

A survey enrolling 814 schoolchildren was conducted immediately after a peak epidemic in the 1988-1989 influenza season and then a case-control study for influenza-like illness (ILI) was carried out using information concerning illness onset and usual lifestyle. Based on the analysis of the correlations among symptoms and actions taken due to symptoms, cases were defined as those with fever greater than or equal to 38 degrees C and subsequent absenteeism and medical consultation during peak epidemic; within this, mild-ILI (MILI) was defined as fever greater than or equal to 38 degrees C and less than 39 degrees C, and severe-ILI (SILI) as fever greater than or equal to 39 degrees C. Controls were defined as those with no symptoms (NS) during that period. Adjusted odds ratios (OR) were obtained through an unconditional logistic regression model between the MILI (80) or SILI (48) and NS (196) groups from among respondents (803). For MILI, increased risks were observed for easily-inflamed tonsils (OR = 3.0, 95% CI: 1.7-5.4); and larger family size (1.9, 1.1-3.4); with decreased risks for higher school grades (0.4, 0.2-0.9); frequent intake of vegetables or fruits other than green/yellow vegetables (0.5, 0.3-1.0); and larger room space per capita (0.4, 0.2-0.9). For SILI, there were increased risks for easily-inflamed tonsils (3.8, 1.8-8.1) and history of doctor-diagnosed asthma (2.9, 1.2-6.7); and decreased risks for higher grades (0.2, 0.1-0.6), frequent intake of milk or dairy products (0.3, 0.1-0.6) and vaccination (0.3, 0.1-0.8).