Cigarette smoking and cervical cancer risk: an evaluation based on a systematic review and meta-analysis among Japanese women.

BACKGROUND: There is a body of evidence to suggest that cigarette smoking increases the risk of cervical cancer in women, but no study has examined the magnitude of the association in Japanese women. Here, we evaluated the association between cigarette smoking and the risk of cervical cancer in Japanese women based on a systematic review of epidemiological evidence. METHODS: Original data were obtained from a MEDLINE search using PubMed or from a search of the 'Ichushi' database, as well as by a manual search. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as evaluated previously by the International Agency for Research on Cancer. Meta-analysis of associations was also conducted to obtain a summarized overview of the data. RESULTS: We identified two cohort studies and three case-control studies. All five studies had indicated strong positive associations between cigarette smoking and the risk of cervical cancer. Our summary estimate indicated that the relative risk (RR) for individuals who had ever-smoked relative to never-smokers was 2.03 (95% confidence interval: 1.49-2.57). Four studies had also demonstrated dose-response relationships between cigarette smoking and the risk of cervical cancer. CONCLUSION: We conclude that there is convincing evidence that cigarette smoking increases the risk of cervical cancer among Japanese women.

Evidence-based cancer prevention recommendations for Japanese.

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study.

BACKGROUND: We examined the associations of intakes of vegetables and carotenes with risk of prostate cancer in Japanese. METHODS: A total of 15,471 Japanese men participating in the Japan Collaborative Cohort study completed a questionnaire including food intake. Of them, 143 incident prostate cancers were documented. We examined the associations stated above by using Cox proportional hazard model. RESULTS: Vegetable intake was not associated with the risk of prostate cancer, but so was dietary alpha-carotene intake. The multivariable hazard ratio (95%CI) in the secondary highest and highest quintiles of alpha-carotene intake was 0.50 (0.26-0.98) (P=0.043) and 0.46 (0.22-0.97) (P=0.041) (P for trend=0.224), respectively. Beta-carotene intake was not associated with the risk of prostate cancer. CONCLUSION: Alpha-carotene intake was associated with lower risk of prostate cancer among Japanese.

Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies.

BACKGROUND: Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. METHODS: In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. RESULTS: During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77-1.03; P for trend = 0.13) among men and 0.83 (0.67-1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63-0.97; P for trend = 0.02) among men. CONCLUSIONS: This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men.

Body mass index and breast cancer risk in Japan: a pooled analysis of eight population-based cohort studies.

BACKGROUND: A positive association between body mass index (BMI) and breast cancer risk among postmenopausal women has been reported, and a weak inverse association has been suggested among premenopausal women from studies in the Western population. The effects of BMI on breast cancer have remained unclear among the Asian population, especially in premenopausal women. METHODS: We assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. Cancer incidence was mainly confirmed through regional population-based cancer registries and/or through active patient notification from major local hospitals. Breast cancer was defined as code C50 according to ICD10. Pooled estimates of the hazard ratios (HRs) and 95% confidence interval (CIs) for breast cancer were calculated using random-effects models. RESULTS: Analytic subjects were 183 940 women, 1783 of whom had breast cancer during 2 194 211 person-years of follow-up. A positive association between BMI and the risk of postmenopausal breast cancer was observed (trend P<0.001). The HRs for premenopausal breast cancer were 1.05 (95% CI 0.56-1.99), 1.07 (95% CI 0.76-1.52), 0.91 (95% CI 0.64-1.30), 1.15 (95% CI 0.76-1.73), 1.45 (95% CI 0.71-2.94), and 2.25 (95% CI 1.10-4.60), respectively, in BMIs of <19, 19 to <21, 21 to <23, 25 to <27, 27 to <30, and ≥30 kg/m2. These results were not substantially altered after excluding the patients who were diagnosed with breast cancer in the first 2 years of follow-up. CONCLUSIONS: The increased risk of postmenopausal breast cancer among women with higher BMIs was confirmed in Japanese. A borderline-significant positive association between BMI and premenopausal breast cancer was observed, suggesting that body mass in Asian women might have opposite effects on breast cancer compared with Western women.

Dietary patterns and risk of cardiovascular deaths among middle-aged Japanese: JACC Study.

BACKGROUND AND AIMS: Little evidence showed the association between dietary patterns and cardiovascular disease among Japanese. The objective of this study was to examine whether dietary patterns are associated with cardiovascular disease among middle-aged Japanese. METHODS AND RESULTS: At baseline (1988-1990), 26,598 men and 37,439 women aged 40-79 years enrolled in the Japan Collaborative Cohort (JACC) Study. During the follow-up through 2003, 578 men and 499 women died from stroke, and 272 men and 207 women died from coronary heart disease. We identified three major dietary patterns, 'vegetable', 'animal food' and 'dairy product', by factor analysis for both sexes. The multivariable hazard ratio (HR) and 95% confidence intervals of mortality from total cardiovascular disease in the highest versus lowest quintiles of the vegetable pattern were 0.93 (0.78-1.13), p for trend=0.73 for men and 0.82 (0.67-1.00), p for trend=0.04 for women. The respective HRs of mortality from stroke in the highest versus lowest quintiles of the dairy product pattern were 0.65 (0.49-0.86), p for trend=0.01 for men and 0.70 (0.51-0.97), p for trend=0.02 for women, and those of total cardiovascular disease were 0.89 (0.74-1.08), p for trend=0.23 for men and 0.76 (0.61-0.94), p for trend=0.01 for women. The animal food pattern was not associated with mortality from stroke, coronary heart disease or total cardiovascular disease for either sex. CONCLUSION: We found that 'vegetable' and 'dairy product' patterns were associated with lower morality from cardiovascular disease, while the 'animal food' pattern was not associated with mortality from cardiovascular disease among Japanese.

Association between body mass index and the colorectal cancer risk in Japan: pooled analysis of population-based cohort studies in Japan.

BACKGROUND: Obesity has been recognized as important risk factors for colorectal cancer. However, limited evidence is available on colorectal cancer and body mass index (BMI) in Asian population. METHODS: We conducted a pooled analysis of eight population-based prospective cohorts studies in Japan with more than 300,000 subjects to evaluate an impact of obesity in terms of BMI on colorectal cancer risk with unified categories. We estimated summary hazard ratio (HR) by pooling of study-specific HR for BMI categories with random effect model. RESULTS: We found a significant positive association between BMI and colorectal cancer risk in male and female. Adjusted HRs for 1 kg/m(2) increase were 1.03 [95% confidence interval (CI) 1.02-1.04] for males and 1.02 (95% CI 1.00-1.03) for females. The association was stronger in colon, especially in proximal colon, relative to rectum. Males showed a stronger association than females. Population attributable fraction for colorectal cancer by BMI ≥ 25 kg/m(2) was 3.62% (95% CI 1.91-5.30) for males and 2.62% (95% CI 0.74-4.47) for females. CONCLUSIONS: We found significant association between BMI and colorectal cancer risk by pooling of data from cohort studies with considerable number of subjects among Japanese population. This information is important in cancer control planning, especially in Asian population.

Associations of diabetes mellitus with site-specific cancer mortality in the Asia-Pacific region.

BACKGROUND: Owing to the increasing prevalence of obesity and diabetes in Asia, and the paucity of studies, we examined the influence of raised blood glucose and diabetes on cancer mortality risk. MATERIALS AND METHODS: Thirty-six cohort Asian and Australasian studies provided 367, 361 participants (74% from Asia); 6% had diabetes at baseline. Associations between diabetes and site-specific cancer mortality were estimated using time-dependent Cox models, stratified by study and sex, and adjusted for age. RESULTS: During a median follow-up of 4.0 years, there were 5992 deaths due to cancer (74% Asian; 41% female). Participants with diabetes had 23% greater risk of mortality from all-cause cancer compared with those without: hazard ratio (HR) 1.23 [95% confidence interval (CI) 1.12, 1.35]. Diabetes was associated with mortality due to cancer of the liver (HR 1.51; 95% CI 1.19, 1.91), pancreas (HR 1.78; 95% CI 1.20, 2.65), and, less strongly, colorectum (HR 1.32; 95% CI 0.98, 1.78). There was no evidence of sex- or region-specific differences in these associations. The population attributable fractions for cancer mortality due to diabetes were generally higher for Asia compared with non-Asian populations. CONCLUSION: Diabetes is associated with increased mortality from selected cancers in Asian and non-Asian populations.

Green tea consumption and gastric cancer in Japanese: a pooled analysis of six cohort studies.

BACKGROUND: Previous experimental studies have suggested many possible anti-cancer mechanisms for green tea, but epidemiological evidence for the effect of green tea consumption on gastric cancer risk is conflicting. OBJECTIVE: To examine the association between green tea consumption and gastric cancer. METHODS: We analysed original data from six cohort studies that measured green tea consumption using validated questionnaires at baseline. Hazard ratios (HRs) in the individual studies were calculated, with adjustment for a common set of variables, and combined using a random-effects model. RESULTS: During 2 285 968 person-years of follow-up for a total of 219 080 subjects, 3577 cases of gastric cancer were identified. Compared with those drinking <1 cup/day, no significant risk reduction for gastric cancer was observed with increased green tea consumption in men, even in stratified analyses by smoking status and subsite. In women, however, a significantly decreased risk was observed for those with consumption of > or =5 cups/day (multivariate-adjusted pooled HR = 0.79, 95% confidence interval (CI) = 0.65 to 0.96). This decrease was also significant for the distal subsite (HR = 0.70, 95% CI = 0.50 to 0.96). In contrast, a lack of association for proximal gastric cancer was consistently seen in both men and women. CONCLUSIONS: Green tea may decrease the risk of distal gastric cancer in women.

Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population.

OBJECTIVE AND METHODS: To characterise the epidemiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) in the Japanese population, this study performed a nationwide assessment of the prevalence and incidence rates in Japan. RESULTS: The prevalence rate per 100 000 was 1.61 in the total population; 2.01 in males and 1.23 in females. The age dependent prevalence rates were 0.23 in juveniles (<15 years old), 1.50 in young adults (15-55 years) and 2.31 in elderly adults (>55 years). The sex and age dependent prevalence rates were 0.22 in males and 0.24 in females in juveniles, 1.81 in males and 1.19 in females in young adults, and 3.12 in males and 1.64 in females in elderly adults. The annual incidence rate per 100 000 was 0.48 in the total population, 0.58 in males and 0.38 in females. The age dependent incidence rate was 0.06 in juveniles, 0.40 in young adults and 0.73 in elderly adults. The sex and age dependent incidence rate was 0.05 in males and 0.08 in females in juveniles, 0.50 in males and 0.30 in females in young adults, and 0.93 in males and 0.58 in females in elderly adults. Both the prevalence and incidence rates were very similar throughout the eight geographical areas studied, from the northern to the southern parts of Japan. CONCLUSIONS: The prevalence and incidence rates were similar to those reported in the Caucasian population. The pathogenic background is suggested to be common throughout the different races and geographic areas, while gender and age effects should be taken into account in the pathogenesis of CIDP.

Cigarette smoking, alcohol drinking, and oral and pharyngeal cancer mortality in Japan.

OBJECTIVES: To prospectively examine the association of cigarette smoking and alcohol drinking with oral and pharyngeal carcinogenesis, we analyzed data from a nation-wide large-scale cohort study in Japan. METHODS: A total of 34 136 men and 43 711 women aged 40-79 years were included in the study. The Cox proportional hazard model was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of oral and pharyngeal cancer for smoking and drinking by sex, while adjusting for age, consumption of green tea, preference for salty foods, and consumption of green yellow vegetables. RESULTS: Current smokers were found to have a higher risk of death caused by oral and pharyngeal cancer compared with non-smokers in both sexes: the RR was 2.6 (95% CI: 1.0-6.7) in men and 8.2 (95% CI: 2.1-32.1) in women. Men who drank more than 46 g ethanol per day had an approximately threefold increased risk of oral and pharyngeal cancer. Simultaneous exposure to both factors was significantly associated with an elevated risk of oral and pharyngeal cancer (RR: 3.3, 95% CI: 1.1-9.6). CONCLUSIONS: The result supports the carcinogenic effect of cigarette smoking and alcohol drinking on the oral cavity and pharynx.

Familial aggregation and coaggregation of history of hypertension and stroke.

We attempted to evaluate familial aggregation and coaggregation of history of hypertension and stroke. Past and family history of hypertension and stroke for 83 089 probands and their relatives were obtained from a data set for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education (JACC Study), which was initiated from 1988 to 1990. First, evaluation was performed for familial aggregation of each of two disorders using ordinal logistic regression of the generalized estimation equations (GEE) to account for dependence of observations within families. Secondly, in order to evaluate the familial congregation of the history of hypertension and stroke, a GEE-based multivariate probed predictive model was applied. After adjusting for the proband's age, level of obesity, smoking status, drinking status, habitation area, and the gender and type of the relatives, the estimated odds ratios for the intraindividual clustering and familial aggregation of the disease history showed statistically significant relationships. In addition, the history of the two disorders showed a significant relationship in terms of familial coaggregation independently of the aggregation of each disorder itself. Our results confirmed that hypertension and stroke coaggregate strongly within families through possible effects of genetic factors, which, alone or in conjunction with environmental factors, influence susceptibility to both hypertension and stroke.

Newly developed ST-T abnormalities on the electrocardiogram and chronologic changes in cardiovascular risk factors.

An ST-T abnormality on an electrocardiogram (ECG) is known to independently predict subsequent morbidity and mortality from cardiovascular diseases. But how ST-T abnormality develops in relation to chronologic changes in cardiovascular risk factors has not been fully discussed. Sixty-eight men whose ECG had been initially normal but who exhibited ST-T abnormality later (ST-T subjects) were identified among 21,579 apparently healthy adults who had undergone comprehensive health examinations for > 10 years. Echocardiography proved that 26 of 29 examinees among ST-T subjects had left ventricular hypertrophy. Antihypertensive drugs were given to 26 of the ST-T subjects. Their cardiovascular risk factors were chronologically reviewed from 10 years before the onset of definite ST-T abnormality, and were compared with those of 68 men whose ECG had remained consistently normal for 10 years (controls). Mean values of systolic and diastolic blood pressure gradually increased over 10 years (from 127/78 to 144/84 mm Hg) among ST-T subjects, but showed little change (from 122/76 to 124/77 mm Hg) during the same period in controls. The time course of blood pressure over 10 years was similar in ST-T subjects, irrespective of final blood pressure level. Mean serum cholesterol and glucose increased over 10 years in both ST-T and control subjects. Uric acid decreased over 10 years (from 6.1 to 5.6 mg/dl) only in ST-T subjects. Multivariate analysis revealed that blood pressure and uric acid before onset of ST-T abnormality were chronologically changed independent of other risk factors. The time course of risk factors may be of great importance in the development of cardiovascular disorders.

Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross-sectional study in Japan.

PURPOSE: To investigate the associations of fatty acid intake with seasonal allergic rhinoconjunctivitis. METHODS: The study subjects consisted of 1012 women aged 22 to 57 years (mean age +/- SD: 36.5+/-7.7 years), who had graduated from the Aichi Prefectural Junior College of Nursing, Nagoya, Japan. They completed a self-administered questionnaire on symptoms of the disease in August 1998. Symptoms of seasonal allergic rhinoconjunctivitis in spring were determined by response to the questionnaire, and fatty acid intake was estimated using a food frequency questionnaire. Odds ratios (ORs) were computed using unconditional logistic models to assess the strength of associations between the symptoms and fatty acid intake. RESULTS: An increasing trend in the ORs was observed with increasing dietary intake of n-6 polyunsaturated fatty acids. After adjustment for potential confounders, the ORs for the second, third, and highest quartiles of intake relative to the lowest were 1.28 [95% confidence interval (CI), 0.78-2.10], 1.55 (0.96-2.50), and 1.74 (1.09-2.77), respectively (trend p = 0.015). Consumption of saturated, monounsaturated, and n-3 polyunsaturated fatty acids was not significantly related to the symptoms. CONCLUSIONS: Dietary intake of n-6 polyunsaturated fatty acids was positively associated with seasonal allergic rhinoconjunctivitis in spring.

Risk modification in lung cancer by a dietary intake of preserved foods and soyfoods: findings from a case-control study in Okinawa, Japan.

To disclose the association of dietary intake of preserved foods and soyfoods with lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan, from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (1) The more the miso soup intake, the higher the risk (test for trend: P = 0.001 for males; P = 0.043 for females). (2) Frequent intake of pickles (excluding salted fish) tended to be linked with an elevated risk in males. The adjusted odds ratio (OR) for once or twice per week or more, relative to less than once a month was 1.88 (95% confidence interval (CI): 1.26-2.81). (3) Frequent intake of soybeans was associated with a decreased risk in men (OR: 0.63, 95% CI: 0.40-0.98 for once or twice per week or more, relative to less than once a month). (4) Daily consumers of tofu were at a decreased risk, particularly for squamous cell carcinoma; the OR (95% CI) being 0.55 (0.34-0.89) in males and 0.14 (0.02-0.89) in females. These findings suggested deleterious effects of preserved foods and protective ones of soyfoods rich in isoflavones.

Epidemiology of breast cancer in Japan.

BACKGROUND: A recent increase in the numbers of deaths and incident cases of breast cancer among Japanese women stimulated the authors to summarize the trends in female breast cancer mortality and incidence rates in Japan. METHODS: The number of deaths from female breast cancer was obtained from the national vital statistics. Estimated incidence rates, based on several cancer registries, were also used for the analyses. The trends in the age-adjusted and age-specific rates were examined. Age and birth cohort effects on the incidence and mortality rates were examined, using multiplicative models. RESULTS: The age-adjusted mortality rate has been increasing since the 1960s (4.1 per 100,000 population in 1950 and 6.6 in 1991, adjusted by the World Population). The age-adjusted incidence rate has also been rising since 1975. Age-specific rates have been increasing particularly in the age range 40-79 years. The multiplicative models disclosed an increasing cohort effect for the mortality and incidence rates among women born after 1900. Decreasing mortality and incidence rates after menopause were ascribed by the models to strong cohort effects. CONCLUSIONS: The recently increasing trend was believed to be consistent with changed risk factors among Japanese women. The age effect on female breast cancer incidence rate in Japan was concluded to be similar to that in Western populations.

Cigarette smoking as a risk factor for chronic pancreatitis: a case-control study in Japan. Research Committee on Intractable Pancreatic Diseases.

We conducted a hospital-based, case-control study to examine the association of cigarette smoking with chronic pancreatitis. Ninety-one male patients with chronic pancreatitis newly diagnosed from July 1997 to December 1998 were recruited as cases, and 175 controls were individually matched to each case for gender, age (+/- 5 years), hospital, and time of the first visit to a hospital (+/- 1 year). A self-administered questionnaire was used to collect information on tobacco and alcohol use, diet, and other factors. The odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by multiple conditional logistic models, adjusting for body mass index, education level, and alcohol consumption. Compared with nonsmokers, the ORs (95% CIs) were 7.8 (2.2-27.3) for all current smokers, and 14.7 (3.1-69.9), 5.5 (1.5-20.1), 12.2 (2.4-71.0) for those consuming < 20, 20-39, and > or = 40 cigarettes per day, respectively. Much greater risk was observed for those who had smoked for > or = 25 years. Risk of chronic pancreatitis significantly increased with increasing cumulative amount of smoking (p < 0.05). Analysis for the effect of combined use of tobacco and alcohol showed that cigarette smoking was associated with the higher risk in both of the two alcohol consumption levels. Our findings indicated that cigarette smoking may be an independent and significant risk factor for chronic pancreatitis.

Incidence and prevalence of inflammatory bowel disease in Japan: nationwide epidemiological survey during the year 1991.

The aim of this nationwide study was to determine the recent incidence and prevalence of inflammatory bowel disease, i.e., Crohn's disease (CD) and ulcerative colitis (UC), in Japan. We mailed out a preliminary examination sheet with diagnostic criteria, asking about the presence of patients with inflammatory bowel disease, to all hospitals in Japan that have more than 200 beds for general use. The rate of reply was 60.93%. A total of 4243 patients with CD were reported. The incidence per 100 000 population per annum was 0.51 (0.71 in males, 0.32 in females). The prevalence per 100 000 population per annum was 5.85 (7.94 in males, 3.83 in females). Peak age at onset was 20-24 years in males and 15-19 years in females. A total of 12559 cases of UC were reported. The incidence per 100 000 population per annum was 1.95 (2.23 in males, 1.68 in females). The prevalence per 100 000 population per annum was 18.12 (18.70 in males, 18.17 in females). Peak age at onset was 20-24 years in males and 25-29 years in females.

Nationwide epidemiological survey of chronic pancreatitis in Japan.

The aim of this study was to estimate the number of patients treated for chronic pancreatitis in 1994 in Japan and to explore the clinico-epidemiological features of chronic pancreatitis. Two surveys were conducted. Stratified random sampling was used to select departments in which patients with chronic pancreatitis were treated, and two different questionnaires were administered to obtain relevant information. From the first survey, the total number of patients treated for chronic pancreatitis in Japan in the year 1994 was estimated as 32,000 (95% confidence interval, 25,000-39,000). Clinico-epidemiological features, based on the 2,523 patients reported from the second survey, were subsequently clarified. The sex ratio (male/female) of the patients was 3.5. Alcoholic pancreatitis was the most common type in males (68.5%), and idiopathic pancreatitis in females (69.6%). Compared with the findings in the last survey in 1985, the proportion of patients with alcoholic pancreatitis has decreased slightly, from 58.7% to 55.5%, while that of idiopathic chronic pancreatitis has increased in both males and females. Patients diagnosed by advanced techniques such as computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) accounted for 68.1% of the total. The number of patients with chronic pancreatitis treated in 1994 in Japan, was estimated as 32,000, with an overall prevalence rate of 45.4 per 100,000 population in males and 12.4 per 100,000 population in females.

Smoking and neovascular form of age related macular degeneration in late middle aged males: findings from a case-control study in Japan. Research Committee on Chorioretinal Degenerations.

AIMS: The risk of smoking habits for developing the neovascular form of age related macular degeneration (neovascular form of AMD) were studied by a case-control study in Japan. METHODS: 56 male patients with the neovascular form of AMD and 82 healthy male controls, aged 50 to 69 years, were enrolled. A self administered questionnaire provided necessary information for the study subjects. Questions on smoking included whether the study subjects have ever smoked or not, and if smoked, depth of smoke inhalation, use of extra filter, age at starting smoking, average number of cigarettes smoked per day, and duration of smoking. When a smoker had stopped smoking, age at cessation was also recorded. Unconditional logistic analysis was adapted to calculate age adjusted odds ratios and their 95% confidence intervals (CIs) for smoking related factors. RESULTS: Age adjusted odds ratio of developing the neovascular form of AMD was 2.97 (95% CI 1.00-8.84) for current smokers and 2.09 (0.71-6.13) for ex smokers, compared with non-smokers. All smoking habit/smoking history related variables such as use of extra filter, smoke inhalation level, age at starting smoking, duration of smoking, and Brinkman index were found to be significantly related to an increased risk of the neovascular form of AMD. CONCLUSIONS: Suggested is the strong possibility that cigarette smoking enhances the neovascular form of AMD risk in late middle aged males, though the magnitude of risk by smoking variables might be overestimated, in part, because of health oriented controls.