Comparison of All Solid Cancer Mortality and Incidence Dose-Response in the Life Span Study of Atomic Bomb Survivors, 1958-2009.

Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.

Individual response of humans to ionising radiation: governing factors and importance for radiological protection.

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

DS02R1: Improvements to Atomic Bomb Survivors' Input Data and Implementation of Dosimetry System 2002 (DS02) and Resulting Changes in Estimated Doses.

Individual dose estimates calculated by Dosimetry System 2002 (DS02) for the Life Span Study (LSS) of atomic bomb survivors are based on input data that specify location and shielding at the time of the bombing (ATB). A multi-year effort to improve information on survivors' locations ATB has recently been completed, along with comprehensive improvements in their terrain shielding input data and several improvements to computational algorithms used in combination with DS02 at RERF. Improvements began with a thorough review and prioritization of original questionnaire data on location and shielding that were taken from survivors or their proxies in the period 1949-1963. Related source documents varied in level of detail, from relatively simple lists to carefully-constructed technical drawings of structural and other shielding and surrounding neighborhoods. Systematic errors were reduced in this work by restoring the original precision of map coordinates that had been truncated due to limitations in early data processing equipment and by correcting distortions in the old (WWII-era) maps originally used to specify survivors' positions, among other improvements. Distortion errors were corrected by aligning the old maps and neighborhood drawings to orthophotographic mosaics of the cities that were newly constructed from pre-bombing aerial photographs. Random errors that were reduced included simple transcription errors and mistakes in identifying survivors' locations on the old maps. Terrain shielding input data that had been originally estimated for limited groups of survivors using older methods and data sources were completely re-estimated for all survivors using new digital terrain elevation data. Improvements to algorithms included a fix to an error in the DS02 code for coupling house and terrain shielding, a correction for elevation at the survivor's location in calculating angles to the horizon used for terrain shielding input, an improved method for truncating high dose estimates to 4 Gy to reduce the effect of dose error, and improved methods for calculating averaged shielding transmission factors that are used to calculate doses for survivors without detailed shielding input data. Input data changes are summarized and described here in some detail, along with the resulting changes in dose estimates and a simple description of changes in risk estimates for solid cancer mortality. This and future RERF publications will refer to the new dose estimates described herein as "DS02R1 doses."

Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes.

Initial Report for the Radiation Effects Research Foundation F1 Mail Survey.

To study the full health effects of parental radiation exposure on the children of the atomic bomb survivors, the Radiation Effects Research Foundation developed a cohort of 76,814 children born to atomic bomb survivors (F1 generation) to assess cancer incidence and mortality from common adult diseases. In analyzing radiationassociated health information, it is important to be able to adjust for sociodemographic and lifestyle variations that may affect health. In order to gain this and other background information on the F1 cohort and to determine willingness to participate in a related clinical study, the F1 Mail Survey Questionnaire was designed with questions corresponding to relevant health, sociodemographic, and lifestyle indicators. Between the years 2000 and 2006, the survey was sent to a subset of the F1 Mortality Cohort. A total of 16,183 surveys were completed and returned: 10,980 surveys from Hiroshima residents and 5,203 from Nagasaki residents. The response rate was 65.6%, varying somewhat across parental exposure category, city, gender, and year of birth. Differences in health and lifestyle were noted in several variables on comparison across city and gender. No major differences in health, lifestyle, sociodemographics, or disease were seen across parental exposure categories, though statistically significant tests for heterogeneity and linear trend revealed some possible changes with dose. The data described herein provide a foundation for studies in the future.

Radiation-related risks of non-cancer outcomes in the atomic bomb survivors.

Risks of non-cancer outcomes after exposure to atomic bomb (A-bomb) radiation have been evaluated among the Life Span Study (LSS) cohort and its subcohort, the Adult Health Study (AHS). Information regarding non-cancer outcomes in the LSS is obtained from death certificates. In the AHS, members undergo clinical examinations biennially to determine their health status. Many AHS studies have been limited to participants attending the clinic over a limited period, and therefore have varying degrees of inferential utility; as such, care is required for comparison with the LSS results. Disease structure of non-cancer diseases in Japan has changed over the long follow-up period since the end of World War II. The health status of the A-bomb survivors may be associated with the hardships of living in a devastated city and impoverished country following the prolonged war effort, in addition to the direct effects of radiation exposure. Radiation-related risk of cardiovascular disease may have increased due to radiation-related increased risk of hypertension and other secondary associations, and the risk of atherosclerotic disorders has also been reported recently. These results should be interpreted with caution because of changes in disease definitions over the follow-up period. The radiation-related risk of non-cancer respiratory diseases also appears to have increased over the follow-up period, but the shapes of the dose-response curves have shown little consistency.

Cardiovascular disease mortality of A-bomb survivors and the healthy survivor selection effect.

The latest A-bomb survivor data for cardiovascular diseases are analysed to investigate whether in the first years after the bombings the baseline rates of proximal survivors were markedly different compared with those of the distal survivors. This phenomenon relates to a healthy survivor selection effect. This question is important for the decision whether to include or exclude the early years of follow-up when analysing the biological effects from acute low and high dose exposures following the nuclear weapons explosions in Hiroshima and Nagasaki. The present study shows that for cerebrovascular diseases and heart diseases the baseline rates are not significantly different in the first two decades of follow-up. Thus, for these two detrimental health outcomes, there is no need to exclude distal survivors and the first decades of follow-up time when investigating the shapes of the related dose-responses.

A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

Low vitamin and carotenoid levels are related to cerebral white matter lesions.

PURPOSE: To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. SUBJECTS AND METHODS: Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. RESULTS: Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking. CONCLUSION: Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.

Invited commentary: missing doses in the life span study of Japanese atomic bomb survivors.

The Life Span Study is a long-term epidemiologic cohort study of survivors of the atomic bombs dropped on Hiroshima and Nagasaki, Japan. In this issue of the Journal, Richardson et al. (Am J Epidemiol. 2013;177(6):562-568) suggest that those who died in the earliest years of follow-up were more likely to have a missing dose of radiation exposure assigned, leading to a bias in the radiation risk estimates. We show that nearly all members of the cohort had shielding information recorded before the beginning of follow-up and that much of the alleged bias that Richardson et al. describe simply reflects the geographic distribution of shielding conditions for which reliable dosimetry was impossible.

Impact of smoking on mortality and life expectancy in Japanese smokers: a prospective cohort study.

OBJECTIVE: To investigate the impact of smoking on overall mortality and life expectancy in a large Japanese population, including some who smoked throughout adult life. DESIGN: The Life Span Study, a population-based prospective study, initiated in 1950. SETTING: Hiroshima and Nagasaki, Japan. PARTICIPANTS: Smoking status for 27,311 men and 40,662 women was obtained during 1963-92. Mortality from one year after first ascertainment of smoking status until 1 January 2008 has been analysed. MAIN OUTCOME MEASURES: Mortality from all causes in current, former, and never smokers. RESULTS: Smokers born in later decades tended to smoke more cigarettes per day than those born earlier, and to have started smoking at a younger age. Among those born during 1920-45 (median 1933) and who started smoking before age 20 years, men smoked on average 23 cigarettes/day, while women smoked 17 cigarettes/day, and, for those who continued smoking, overall mortality was more than doubled in both sexes (rate ratios versus never smokers: men 2.21 (95% confidence interval 1.97 to 2.48), women 2.61 (1.98 to 3.44)) and life expectancy was reduced by almost a decade (8 years for men, 10 years for women). Those who stopped smoking before age 35 avoided almost all of the excess risk among continuing smokers, while those who stopped smoking before age 45 avoided most of it. CONCLUSIONS: The lower smoking related hazards reported previously in Japan may have been due to earlier birth cohorts starting to smoke when older and smoking fewer cigarettes per day. In Japan, as elsewhere, those who start smoking in early adult life and continue smoking lose on average about a decade of life. Much of the risk can, however, be avoided by giving up smoking before age 35, and preferably well before age 35.

Effects of radiation and lifestyle factors on risks of urothelial carcinoma in the Life Span Study of atomic bomb survivors.

Among the Life Span Study (LSS) of Atomic-bomb survivors, recent estimates showed that unspecified bladder cancer had high radiation sensitivity with a notably high female-to-male excess relative risk (ERR) per radiation dose ratio and were the only sites for which the ERR did not decrease with attained age. These findings, however, did not consider lifestyle factors, which could potentially confound or modify the risk estimates. This study estimated the radiation risks of the most prevalent subtype of urinary tract cancer, urothelial carcinoma, while accounting for smoking, consumption of fruit, vegetables, alcohol and level of education (a surrogate for socioeconomic status). Eligible study subjects included 105,402 (males = 42,890) LSS members who were cancer-free in 1958 and had estimated radiation doses. Members were censored due to loss of follow-up, incident cancer of another type, death, or the end of calendar year 2001. Surveys (by mail or clinical interview) gathered lifestyle data periodically for 1963-1991. There were 63,827 participants in one or more survey. Five hundred seventy-three incident urothelial carcinoma cases occurred, of which 364 occurred after lifestyle information was available. Analyses were performed using Poisson regression methods. The excess relative risk per weighted gray unit (the gamma component plus 10 times the neutron component, Gy(w)) was 1.00 (95% CI: 0.43-1.78) but the risks were not dependent upon age at exposure or attained age. Lifestyle factors other than smoking were not associated with urothelial carcinoma risk. Neither the magnitude of the radiation ERR estimate (1.00 compared to 0.96), nor the female-to-male (F:M) ERR/Gy(w) ratio (3.2 compared to 3.4) were greatly changed after accounting for all lifestyle factors. A multiplicative model of gender-specific radiation and smoking effects was the most revealing though there was no evidence of significant departures from either the additive or multiplicative joint effect models. Among the LSS cohort members with doses greater than 0.005 Gy(w) (average dose 0.21 Gy(w)), the attributable fraction of urothelial carcinoma due to radiation was 7.1% in males and 19.7% in females. Among current smokers, the attributable fraction of urothelial carcinoma due to smoking was 61% in males and 52% in females. Relative risk estimates of smoking risk were approximately two for smokers compared to nonsmokers. After adjustment for lifestyle factors, gender-specific radiation risks and the F:M ERR/Gy(w), the ratios of excess urothelial carcinoma risk were similar to the estimates without adjusting for lifestyle factors. Smoking was the primary factor responsible for excess urothelial carcinoma in this cohort. These findings led us to conclude that the radiation risk estimates of urothelial carcinoma do not appear to be strongly confounded or modified by smoking, consumption of alcohol, fruits, or vegetables, or level of education.

Radiation and cancer risk in atomic-bomb survivors.

With the aim of accurately assessing the effects of radiation exposure in the Japanese atomic-bomb survivors, the Radiation Effects Research Foundation has, over several decades, conducted studies of the Life Span Study (LSS) cohort, comprising 93 000 atomic-bomb survivors and 27 000 controls. Solid cancer: the recent report on solid cancer incidence found that at age 70 years following exposure at age 30 years, solid cancer rates increase by about 35%  Gy(-1) for men and 58% Gy(-1) for women. Age-at-exposure is an important risk modifier. In the case of lung cancer, cigarette smoking has been found to be an important risk modifier. Radiation has similar effects on first-primary and second-primary cancer risks. Finally, radiation-associated increases in cancer rates appear to persist throughout life. Leukaemia: the recent report on leukaemia mortality suggests that radiation effects on leukaemia mortality persisted for more than 50 years. Moreover, significant dose-response for myelodysplastic syndrome was observed in Nagasaki LSS members even 40-60 years after radiation exposure. Future perspective: given the continuing solid cancer increase in the survivor population, the LSS will likely continue to provide important new information on radiation exposure and solid cancer risks for another 15-20 years, especially for those exposed at a young age.

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium.

BACKGROUND: The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case-control studies from Europe and United States. SUBJECTS AND METHODS: We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500,000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking. RESULTS: A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6-25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57 (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS: Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.

Trends of delays in tuberculosis case finding in Japan and associated factors.

SETTING: Nationwide tuberculosis (TB) registry in Japan, 1987-2002. OBJECTIVE: To clarify the trends of patient's delay (PD), doctor's delay (DD) and total delay (TD), their relation and factors associated with the delays. DESIGN: Longitudinal study on trends in delays. Among patients with symptomatic smear-positive pulmonary TB, those with long PD (> or =2 months), DD (> or =1 month) and TD (> or =3 months) were analysed. RESULTS: Long PD rates increased until around 1997, whereas long DD rates decreased markedly from 1995 to 1999. Long TD rates increased until 1997, and decreased slightly thereafter. Men aged 30-59 years had higher rates of long PD, and the long PD rates increased through the 16-year observation period. Day labourers receiving or applying for welfare benefit had the highest rate of long TD, 46.5% during 1995-2002. Teachers and medical doctors showed the greatest increase in long TD rates through the period. CONCLUSION: Long TD was influenced more by PD than DD, and showed an upward trend. However, the long TD rate has declined slightly owing to the recent reduction in long DD. The reduction in DD since 1995 occurred immediately after the introduction of new technology in bacteriological examinations.

The relationship between 24-hour blood pressure readings, subcortical ischemic lesions and vascular dementia.

BACKGROUND: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). METHODS: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP - nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0-0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. RESULTS: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20-9.34), advanced PVH (OR 14.42; 95% CI 5.62-36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37-115.95; reverse dipper: OR 11.95; 95% CI 1.27-112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38-11.17), high daytime (OR 2.06; 95% CI 1.03-4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13-5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03-7.05; reverse dipper: OR 3.78; 95% CI 1.38-10.34) were significantly associated with PVH. CONCLUSIONS: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.

Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct.

BACKGROUND AND PURPOSE: A long-term follow-up study was conducted in patients with lacunar infarct to assess how 24-hour blood pressure monitoring values and MRI findings, in particular lacunar infarcts and diffuse white matter lesions, can predict subsequent development of dementia and vascular events, which include cerebrovascular and cardiovascular events. METHODS: One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up. Documented events comprise the development of dementia and the occurrence of vascular events. The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis. RESULTS: Twenty-six patients developed dementia (0.17/100 patient-years). Male sex (relative risk [RR], 4.2; 95% CI, 1.2 to 14.7), cognitive impairment (RR, 3.0; 95% CI, 1.0 to 8.5), confluent DWML (moderate: RR, 7.1; 95% CI, 1.6 to 31.5; severe: RR, 35.8; 95% CI, 7.2 to 177.3), and nondipping status (RR, 7.1; 95% CI, 2.2 to 22.0) were independent predictors for dementia. Forty-six patients suffered from vascular events (3.11/100 patient-years). Diabetes mellitus (RR, 5.7; 95% CI, 2.7 to 11.9), multiple lacunae (moderate: RR, 6.4; 95% CI, 2.5 to 15.8; severe: RR, 8.5; 95% CI, 3.1 to 23.3), and high 24-hour systolic blood pressure (>145 mm Hg versus <130 mm Hg) (RR, 10.3; 95% CI, 1.3 to 81.3) were independent predictors for vascular events. CONCLUSIONS: Predictors for developing dementia and vascular events appear to differ. Male sex, confluent diffuse white matter lesions, and nondipping status were independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour systolic blood pressure were independent predictors for vascular events.

Dietary habits and risk of lung cancer death in a large-scale cohort study (JACC Study) in Japan by sex and smoking habit.

Lung cancer has increased and is the leading cause of cancer death among Japanese males. The associations of dietary habits with the risk of lung cancer death were evaluated by sex and smoking habits in this study. In the Japan Collaborative Cohort (JACC) Study, a cohort established in 1988 - 90 and consisting of 42 940 males and 55 308 females was observed for lung cancer deaths up to the end of 1997. During the observation period, 446 males and 126 females died of lung cancer. A self-administered food frequency questionnaire was used as the baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. Among males, a high intake of ham and sausages, cheese, green-leafy vegetables, oranges, and other fruits significantly and dose-dependently decreased the risk of lung cancer death. Among females, a high intake of miso-soup, ham and sausages, and liver significantly and almost dose-dependently increased the risk. Vegetables and fruits rich in antioxidative and carcinogenic agents reduced the risk of lung cancer deaths among male smokers more than among female nonsmokers. The results among female nonsmokers were partially consistent with the hypothesis that high fat consumption increases the risk of lung cancer, especially that of adenocarcinoma.

Unique place of Kampo (Japanese traditional medicine) in complementary and alternative medicine: a survey of doctors belonging to the regional medical association in Japan.

Although there are various kinds of complementary and alternative medicine (CAM) therapies, it is conjectured that medical doctors consider individual CAM therapies to be heterogeneous in nature. Therefore, to investigate the relationship among Kampo (Japanese traditional medicine) and other CAM, a survey using a structured, self-administered questionnaire was performed for 540 randomly selected doctors of the Kyoto Medical Association (KMA). The results showed that some form of CAM was practiced by 73% of the KMA doctors. The most common CAM practice was Kampo, which corresponded to 96.1% of CAM-practicing doctors. A smaller percentage of doctors practiced other forms of alternative medicine. Kampo was best known by doctors among other CAM therapies. Almost all doctors believed in the effectiveness of Kampo. Doctors who believed in the effectiveness of Kampo tended to believe that other CAM therapies were also effective. Cluster analysis revealed that Kampo was distant from the other CAM. It was concluded that Kampo was most frequently practiced and most believed by doctors in Japan among CAM therapies. Since Kampo was independent of other CAM therapies, Kampo's place in CAM therapies was very unique in Japan.