Visceral fat volume and the prevalence of colorectal adenoma.

Few epidemiologic investigations of visceral adiposity and colorectal neoplasms have attempted the direct quantification of visceral fat. The authors measured visceral fat volume among middle-aged and elderly Japanese men and women who underwent colonoscopy and positron emission tomography/computed tomography for cancer screening in Tokyo, Japan, between February 2004 and February 2005, and examined the association between visceral adiposity and colorectal adenoma in 1,205 eligible subjects. Odds ratios and 95% confidence intervals for colorectal adenoma were estimated by using an unconditional logistic regression model after adjustment for potential confounders. Despite its high correlation with body mass index, visceral fat volume was associated with the prevalence of colorectal adenoma independently of body mass index in both sexes. After further adjustment for body mass index, the odds ratio of colorectal adenoma for the highest compared with the lowest quartile of visceral fat volume was 1.58 (95% confidence interval: 1.11, 2.24) for men and women combined. Conversely, body mass index was unlikely to modify the association between visceral fat volume and colorectal adenoma (P(interaction) = 0.39). These findings add to accumulating evidence that visceral adiposity exerts an important influence on the pathogenesis of colorectal neoplasms. The mechanisms of this potential association between visceral adiposity and colorectal carcinogenesis warrant further investigation.

Effect of coffee and green tea consumption on the risk of liver cancer: cohort analysis by hepatitis virus infection status.

In spite of their anticarcinogenic potential, the effect of coffee and green tea consumption on the risk of liver cancer has not been clarified prospectively in consideration of hepatitis C (HCV) and B virus (HBV) infection. We examined whether coffee and green tea consumption was associated with a reduced risk of liver cancer by hepatitis virus infection status in the Japan Public Health Center-Based Prospective Study Cohort II. A total of 18,815 subjects ages 40 to 69 years participating in a questionnaire and health checkup survey in 1993 to 1994 were followed for the incidence of liver cancer through 2006. A total of 110 cases of liver cancer were newly documented. Hazard ratios for coffee and green tea consumption categories were calculated with a Cox proportional hazards model. Compared with almost never drinkers, increased coffee consumption was associated with a reduced risk of liver cancer in all subjects (hazard ratio for <1, 1-2, and >or=3 cups/d; P(trend) = 0.67, 0.49, 0.54, and 0.025). A similar risk tendency was observed in those with either or both HCV and HBV infection. In contrast, no association was observed between green tea consumption and the risk of liver cancer in all subjects. Our results suggest that coffee consumption may reduce the risk of liver cancer regardless of HCV and HBV infection status, whereas green tea may not reduce this risk

Impact of metabolic factors on subsequent cancer risk: results from a large-scale population-based cohort study in Japan.

The impact of metabolic factors, which are major risk factors for cardiovascular disease, on total cancer risk has not been clarified. We prospectively examined whether metabolic factors and their aggregates predict the subsequent occurrence of total and major sites of cancer in the Japan Public Health Center-based Prospective Study. A total of 27 724 participants (9548 men and 18 176 women) aged 40-69 years participating in a questionnaire and health checkup survey in 1993-1995 were followed for total cancer incidence through 2004. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for metabolic factors and for two criteria of their aggregates (three or more than three factors and two or more than two additional factors in addition to being overweight) with a Cox proportional hazards model to control for potential confounding factors. In both sexes, the presence of metabolic factors in the aggregate did not predict subsequent occurrence of cancer as a whole. By site, a significant increase in risk was observed for male liver cancer [HR = 1.73, CI = 1.03-2.91 (three or more than three factors); HR = 1.99, CI = 1.11-3.58 (two or more than two additional factors in addition to being overweight)], and female pancreatic cancer [HR = 1.99, CI = 1.00-3.96 (two or more than two additional factors in addition to being overweight)]. For other sites, positive associations were observed only for specific metabolic factors, that is, high triglycerides and male colon cancer (HR = 1.71, CI = 1.11-2.62), and obesity and female breast cancer (HR = 1.75, CI = 1.21-2.55). Metabolic factors in the aggregate may have little impact on total cancer risk in the Japanese population, although the association between specific components and specific cancers suggests an etiologic link between them.

Genetic polymorphisms in estrogen metabolism and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians.

Although many studies have examined associations between single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2 and CYP1B1 genes and breast cancer risk, no study has examined functional SNPs in the CYP3A5 gene and only a small number of studies have been investigated in Japanese populations. To examine the association between six SNPs, CYP1A1(*)2A, CYP1A1(*)2C, CYP1A2(*)1F, CYP1B1 Arg(48)Gly, CYP1B1 Leu(432)Val and CYP3A5*3 and breast cancer risk, therefore, we conducted hospital-based case-control studies in Nagano, Japan and São Paulo, Brazil including 873 pairs (403 Japanese (JJ), 81 Japanese Brazilians (JB) and 389 non-Japanese Brazilians (NJB)). Although we found no significant association in the three populations combined, subgroup analyses revealed statistically significant associations of CYP1A2*1F in NJB, and CYP1B1 Leu(432)Val and CYP3A5*3 in JJ with breast cancer risk. Compared to women with the AA genotype in CYP1A2*1F, the odds ratio (OR) (95% confidence interval (CI)) for NJB with the CC genotype was 0.54 (0.32-0.90); that for JJ with Leu/Val+Val/Val versus Leu/Leu genotype in CYP1B1 Leu(432)Val was 0.68 (0.48-0.97); and that for JJ with (*)3/(*)1+(*)1/(*)1 versus (*)3/(*)3 genotype in CYP3A5*3 was 1.49 (1.10-2.04). Our findings provide further evidence that genetic polymorphisms related to estrogen metabolism may play a role in the development of breast cancer.

Coffee, green tea, and caffeine consumption and subsequent risk of bladder cancer in relation to smoking status: a prospective study in Japan.

Coffee and caffeine consumption are thought to increase the risk of bladder cancer. However, few studies have stratified this risk by smoking status, which is a potential confounder. Here, we investigated the association between coffee, green tea (another major source of caffeine), and caffeine, and bladder cancer incidence in relation to smoking status. We conducted a population-based prospective study in a cohort of Japanese, comprising a total of 49 566 men and 54 874 women aged 40­69 years who reported their coffee and green tea consumption at baseline. During follow-up from 1990 through 2005, 164 men and 42 women were newly diagnosed with bladder cancer. Cigarette smoking was associated with an increased risk of bladder cancer, with a strong dose­response relationship. Coffee was positively associated with bladder cancer risk in men, without statistical significance. When stratified by smoking status, coffee and caffeine consumption were associated with an increased risk of bladder cancer in never- or former-smoking men, with hazard ratios (95% confidence interval) in the highest categories of coffee (one or more cups per day) and caffeine consumption compared with the lowest of 2.24 (95% CI = 1.21­4.16) and 2.05 (95% CI = 1.15­3.66), respectively. In conclusion, cigarette smoking was confirmed as a risk factor for bladder cancer. Coffee and caffeine may be associated with an increased bladder cancer risk in never or former smokers among Japanese men.

Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a population-based prospective cohort of Japanese men and women.

The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women. Several experiment and epidemiological studies have suggested that estrogen might play an inhibitory role in the development of HCC. Because isoflavones have a similar structure as 17beta-estradiol and appear to have an anti-estrogenic effect in women and estrogenic effect in men, we hypothesized that the effect of isoflavones on HCC differs by sex. We investigated the association between isoflavones (genistein and daidzein) and soy products and HCC in Japan in a population-based prospective study in 19,998 Japanese (7,215 men and 12,783 women) aged 40-69 years. During 11.8 years of follow-up, 101 subjects (69 men and 32 women) were newly diagnosed with HCC. Case patients were grouped according to consumption of isoflavones and soy products and stratified by hepatitis virus infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC were calculated by Cox proportional-hazards modeling. In women, genistein and daidzein were dose-dependently associated with an increased risk of HCC, with multivariable HRs for the highest versus lowest tertile of 3.19 (95%CI = 1.13-9.00, p(trend) = 0.03) and 3.90 (95% CI = 1.30-11.69, p(trend) = 0.01), respectively. No association between isoflavones and HCC was observed in men. These results persisted when analysis was restricted to subjects positive for either or both hepatitis C and B virus. In conclusion, isoflavone consumption may be associated with an increased risk of HCC in women. Women with hepatitis virus infection may be advised to abstain from isoflavone consumption. Further studies are warranted to confirm these findings.

Metabolic factors and subsequent risk of hepatocellular carcinoma by hepatitis virus infection status: a large-scale population-based cohort study of Japanese men and women (JPHC Study Cohort II).

OBJECTIVE: The association between metabolic factors and hepatocellular carcinoma (HCC) has not been well clarified. We prospectively examined whether metabolic factors predicts the subsequent risk of HCC in the Japan Public Health Center-based Prospective Study Cohort II, in consideration of hepatitis virus infection status. METHODS: A total of 17,590 subjects aged 40-69 participating in a questionnaire and health checkup survey during 1993-1994 were followed for incidence of HCC through 2006. A total of 102 cases of HCC were newly documented. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for metabolic factors controlling for potential confounding factors. RESULTS: The presence of metabolic factors in the aggregate was associated with a significantly increased risk of HCC, especially with hepatitis virus infection. HCC was positively associated particularly with high glucose (HR = 1.75, CI = 1.11-2.74) and overweight (HR = 2.22, CI = 1.42-3.48). Results were similar when analyses were limited to subjects with HCV infection. CONCLUSIONS: Although metabolic factors in the aggregate may be associated with an increased risk of HCC, the main contributors to this association under HCV infection appear to be overweight and high glucose. Improvement of these factors may be a crucial target in preventing progression to HCC in those with HCV infection.

Effect of alcohol consumption, cigarette smoking and flushing response on esophageal cancer risk: a population-based cohort study (JPHC study).

We examined the effect of alcohol consumption, cigarette smoking and flushing response on esophageal squamous cell carcinoma (ESCC) in a large-scale population-based cohort study. 44,970 middle-aged and older Japanese men were followed. A total of 215 cases of ESCC were newly diagnosed. Alcohol consumption and cigarette smoking are strongly associated with the incidence of ESCC. Heavy alcohol consumption increased the risk of ESCC especially among heavy smokers with the flushing response (HR = 3.41, 95% CI = 2.10-5.51). Strong effect modification was detected in heavy smokers. Our results suggest that heavy alcohol consumption together with heavy smoking may increase the risk of ESCC particularly in individuals with the flushing response.

Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center.

PURPOSE: The incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy. PATIENTS AND METHODS: We conducted a nested case-control study within the Japan Public Health Center-based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone. RESULTS: Plasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; P(trend) = .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; P(trend) = .03) and 0.43 (95% CI, 0.22 to 0.82; P(trend) = .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer. CONCLUSION: Isoflavones may prevent the development of prostate cancer.

Reproductive factors, exogenous female hormone use and colorectal cancer risk: the Japan Public Health Center-based Prospective Study.

Evidence for an association between reproductive factors, exogenous female hormone use, and colorectal cancer risk from previous epidemiological studies remains controversial and information from nonwestern populations is limited. We analyzed this association in the Japan Public Health Center-based Prospective Study, conducted in 48 511 Japanese women aged 40-69 years who responded to a self-administered questionnaire that included history of reproductive factors, exogenous female hormone use, and other factors. During a mean follow-up of 12 years, a total of 538 colorectal cancer cases were newly identified. Age at menarche, menopausal status, history of exogenous female hormone use, parity, number of births, age at first birth, history of breast feeding, and reproductive period (postmenopausal women only) were not associated with colorectal cancer. When colon and rectal cancer were, however, analyzed separately among all women, multivariate-adjusted hazard ratios (95% confidence intervals) for colon cancer for age at first birth of 23-25, 26-29, 30 years or more in comparison to that at 22 years or less were 0.84 (0.64-1.12), 0.73 (0.53-1.01), and 0.66 (0.41-1.09), respectively (P for trend=0.03). These results were strengthened for colon cancer when analysis was restricted to postmenopausal women (P for trend=0.01), but no association was seen in premenopausal women (P for trend=0.59). In contrast, no statistically significant association was found for rectal cancer. These findings suggest that late age at first birth is associated with a reduced risk of colon cancer in postmenopausal Japanese women.

Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study.

Several experimental studies have reported that the anticarcinogenic properties of dietary soy play an important role in preventing colorectal cancer. However, few epidemiologic studies have examined this association in general populations and their findings have been inconsistent. We investigated the association between dietary soy and isoflavone intake and incidence of colorectal cancer in a prospective cohort study of 83,063 Japanese men and women, ages 45 to 74 years. Dietary soy and isoflavone intake was measured through a validated food frequency questionnaire in 1995 and 1998. Throughout 2004, a total of 886 cases of colorectal cancer were newly identified (291 proximal colon, 286 distal colon, and 277 rectum). The hazard ratios and 95% confidence intervals (95% CIs) were estimated by fitting a Cox proportional hazards model. The intake of isoflavones, miso soup, and soy food was not associated with colorectal cancer in either men or women. By colorectal cancer subsite, the risk of proximal colon cancer in men decreased with increasing consumption of isoflavones, miso soup, and soy food. Compared with men in the lowest quartiles of isoflavones, miso soup, and soy food intake, the hazard ratios in the highest quartiles were 0.55 (95% CI, 0.33-0.92), 0.72 (95% CI, 0.43-1.21), and 0.51 (95% CI, 0.30-0.87), respectively. The results showed no association for distal colon and rectal cancer in men or for subsites of colorectal cancer in women. These findings suggest that the intake of isoflavones, miso soup, and soy food has no substantial effect on the risk of colorectal cancer in Japanese men and women.

Coffee consumption and risk of endometrial cancer: a prospective study in Japan.

Coffee has been proposed to decrease the circulating insulin and estrogen levels, which are related to the development of endometrial cancer. However, few studies have prospectively assessed the association between coffee consumption and endometrial cancer. We conducted a population-based prospective cohort study in 53,724 Japanese women aged 40-69 years with no history of cancer at baseline in 1990-1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of endometrial cancer incidence in relation to coffee consumption. All reported p values are 2-tailed. During the 15-year follow-up period, we documented 117 cases of endometrial cancer. Coffee consumption was significantly associated with a decreased risk of endometrial cancer. After adjustment for age, study area, body mass index, menopausal status, age at menopause for postmenopausal women, parity, use of exogenous female hormones, smoking status and by consumption of green vegetables, beef, pork and green tea, the multivariate HRs (95% CI) of endometrial cancer in women who drank coffee /=3 cups/day were 1.00, 0.97 (0.56-1.68), 0.61 (0.39-0.97) and 0.38 (0.16-0.91), respectively (p for trend = 0.007). In contrast, green tea consumption was not significantly associated with a reduced risk of endometrial cancer (p for trend = 0.22). The inverse association between coffee consumption and risk of endometrial cancer was consistently observed in subgroup analyses stratified by potential confounders. Coffee consumption may be associated with a decreased risk of endometrial cancer.

Fruit and vegetable consumption and squamous cell carcinoma of the esophagus in Japan: the JPHC study.

Epidemiological studies have consistently demonstrated a decrease in the risk of esophageal squamous cell carcinoma (SCC) associated with higher fruit and vegetable intake, although the association has been examined predominantly in case-control studies. Here, we conducted a population-based prospective cohort study among middle-aged Japanese men. Lifestyle characteristics were investigated using a self-administered questionnaire, which included a validated food frequency questionnaire with 138 food and beverage items. We followed a total of 38,790 men aged 45-74 years. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for esophageal SCC, with adjustment for potential confounders. During 297,651 person-years of follow-up, a total of 116 men were newly diagnosed with esophageal SCC. An increase in consumption of total fruit and vegetables by 100 grams per day (g/day) was associated with an 11% decrease in the incidence of esophageal SCC (95% CI: 1-21%). In particular, a higher intake of cruciferous vegetables was associated with a significant decrease in risk (HR per 100 g/day: 0.44; 95% CI: 0.23-0.82). Stratified analyses revealed that the beneficial effect of fruits and vegetables was not able to completely offset the harmful effect of tobacco and alcohol. Our findings provide further evidence for the protective role of fruits and vegetables in the development of esophageal SCC. To effectively reduce the burden of this disease, however, priority should be placed on smoking and drinking cessation. Finally, cruciferous vegetables deserve further investigation as foods possibly effective in the prevention of esophageal SCC.

Education in relation to incidence of and mortality from cancer and cardiovascular disease in Japan.

BACKGROUND: Although lower education has been associated with poorer health, few studies have examined whether lower education affects mortality, incidence, both or neither of cancer and cardiovascular disease. METHODS: The authors conducted a population-based prospective cohort study among 39,228 men and women who were aged 40-59 years and lived in four areas in Japan. Information on education and lifestyle variables were obtained by a self-administered questionnaire in 1990. Follow-up until the end of 2002 (for incidence) or 2003 (for mortality) ascertained 2573 and 1251 incident cases of cancer and cardiovascular disease, respectively, and 2430 deaths (1064 from cancer, 548 from cardiovascular disease and 818 from other causes). RESULTS: After adjustment for demographic and lifestyle variables, <10 years of education, as compared with >12 years of education, was associated with significantly higher mortality from all causes [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.05-1.42] and cardiovascular disease (HR = 1.44, 95% CI: 1.01-2.06), but was not associated with higher incidence of cardiovascular disease (HR = 0.96, 95% CI: 0.78-1.18) or higher mortality or incidence of cancer. CONCLUSION: The findings suggest that lower education is associated with higher mortality from all causes and cardiovascular disease among the Japanese population that is not totally attributable to lifestyle differences or higher cardiovascular disease incidence.

Daily total physical activity level and total cancer risk in men and women: results from a large-scale population-based cohort study in Japan.

The impact of total physical activity level on cancer risk has not been fully clarified, particularly in non-Western, relatively lean populations. The authors prospectively examined the association between daily total physical activity (using a metabolic equivalents/day score) and subsequent cancer risk in the Japan Public Health Center-based Prospective Study. A total of 79,771 general-population Japanese men and women aged 45-74 years who responded to a questionnaire in 1995-1999 were followed for total cancer incidence (4,334 cases) through 2004. Compared with subjects in the lowest quartile, increased daily physical activity was associated with a significantly decreased risk of cancer in both sexes. In men, hazard ratios for the second, third, and highest quartiles were 1.00 (95% confidence interval (CI): 0.90, 1.11), 0.96 (95% CI: 0.86, 1.07), and 0.87 (95% CI: 0.78, 0.96), respectively (p for trend = 0.005); in women, hazard ratios were 0.93 (95% CI: 0.82, 1.05), 0.84 (95% CI: 0.73, 0.96), and 0.84 (95% CI: 0.73, 0.97), respectively (p for trend = 0.007). The decreased risk was more clearly observed in women than in men, especially among the elderly and those who regularly engaged in leisure-time sports or physical exercise. By site, decreased risks were observed for cancers of the colon, liver, and pancreas in men and for cancer of the stomach in women. Increased daily physical activity may be beneficial in preventing cancer in a relatively lean population.

Female reproductive factors and the risk of gastric cancer in a large-scale population-based cohort study in Japan (JPHC study).

The incidence of gastric cancer is two-fold to three-fold greater in men than in women. We investigated the reasons for this discrepancy by evaluating the impact of female reproductive factors on gastric cancer risk in the Japan Public Health Center-based Prospective Study. Among the 44,453 women enrolled, 368 cases of gastric cancer were newly diagnosed during follow-up from 1990 to 2004. The influence of female reproductive factors on risk was estimated using a multivariable Cox proportional hazards model after adjustment for potential confounders. Participants were stratified by menopause and gastric cancer status and further subdivided by histological type and anatomic subsite. No statistically significant association between female reproductive factors and gastric cancer risk was seen in general. Compared with those in late menarche (> or =15), however, women in early menarche (< or =12) had a close to 50% decreased risk of stomach cancer (hazard ratio 0.65, 95% confidence interval 0.43-0.98; P trend <0.01). Similar results were obtained in subgroup analyses categorized by histological subtype and anatomic subsite. Although early estrogen exposure may have some protective effect, female reproductive factors may have no substantial influence on gastric cancer development.

Plasma organochlorine levels and subsequent risk of breast cancer among Japanese women: a nested case-control study.

To our knowledge, no prospective study has examined the association between blood levels of organochlorines and breast cancer risk in Asian countries. Here, we tested the hypothesis that higher blood levels of organochlorines are associated with an increased risk of breast cancer in Japanese women. A total of 24,226 women subjects of the Japan Public Health Center-based Prospective Study aged 40 to 69 years who responded to the baseline questionnaire and provided blood in 1990-1995 were followed to December 2002. During 10.7 years follow-up, 144 cases of breast cancer were newly diagnosed. Two matched-controls for each case were selected from the cohort. Plasma levels of p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (beta-HCH) were measured. A conditional logistic regression was used to estimate the odds ratio (OR) of breast cancer according to cholesterol-adjusted organochlorine levels based on 139 matched pairs. We found no statistically significant positive association between plasma organochlorine level and breast cancer risk. Adjusted ORs for p,p'-DDT, HCB, and beta-HCH were less than 1. For p,p'-DDE, adjusted OR for the highest versus lowest quartile was 1.48 (95% confidence interval 0.70-3.13; p for trend=0.25). A stratified analysis by menopausal status showed positive associations for p,p'-DDT and p,p'-DDE in premenopausal but not postmenopausal women, although without statistical significance. Our data do not support the hypothesis that plasma levels of p,p'-DDT, p,p'-DDE, HCB, and beta-HCH are associated with an overall increased risk of breast cancer among Japanese women.

Daily total physical activity level and premature death in men and women: results from a large-scale population-based cohort study in Japan (JPHC study).

PURPOSE: The impact of daily total physical activity level on premature deaths has not been fully clarified in non-Western, relatively lean populations. We prospectively examined the association between daily total physical activity level (METs/day) and subsequent risk of all-cause mortality and mortalities from cancer, heart disease, and cerebrovascular disease. METHODS: A total of 83,034 general Japanese citizens ages 45-74 years who responded to the questionnaire in 1995-1999 were followed for any cause of death through December 2005. Mutlivariate-adjusted hazard ratios were calculated with a Cox proportional hazards model controlling for potential confounding factors. RESULTS: During follow-up, a total of 4564 deaths were recorded. Compared with subjects in the lowest quartile, increased daily total physical activity was associated with a significantly decreased risk of all-cause mortality in both sexes (hazard ratios for the second, third, and highest quartiles were: men, 0.79, 0.82, 0.73 and women, 0.75, 0.64, 0.61, respectively). The decreased risk was observed regardless of age, frequency of leisure-time sports or physical exercise, or obesity status, albeit with a degree of risk attenuation among those with a high body mass index. A significantly decreased risk was similarly observed for death from cancer and heart disease in both sexes, and from cerebrovascular disease in women. CONCLUSION: Greater daily total physical activity level, either from occupation, daily life, or leisure time, may be of benefit in preventing premature death.

Alcohol and risk of lung cancer among Japanese men: data from a large-scale population-based cohort study, the JPHC study.

OBJECTIVE: Although large-scale studies, including meta-analyses, on the association between alcohol consumption and lung cancer have been reported, the risk of lung cancer in extremely high consumption groups (>or=450 g ethanol/week) in both current smokers and nonsmokers remains unclear. Here, we investigated the association between alcohol consumption and lung cancer incidence. METHODS: We conducted a population-based prospective cohort study in 46,347 Japanese men aged 40-69 years with no history of cancer at baseline in 1990-1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of lung cancer incidence according to alcohol consumption. RESULTS: During the 14-year follow-up period, we documented 651 cases of lung cancer. We found a positive association between alcohol consumption and lung cancer risk confined to current smokers. Compared with occasional drinkers, the multivariate HRs (95% CI) in the highest category (>or=450 g ethanol/week) were 1.31 (0.89-1.94) among total participants, 0.58 (0.26-1.30) (p for trend = 0.49) among nonsmokers, and 1.69 (1.05-2.72) (p for trend = 0.02) among current smokers. CONCLUSIONS: Among this population with a large variation in alcohol consumption, alcohol consumption was not an independent risk factor for lung cancer except for current smokers.

Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias.

BACKGROUND: The etiology of hypospadias is regarded as a complex disorder with both genetic and environmental contributions. Although alterations in androgen activity have been associated with hypospadias, few associations with estrogen activity have been documented. Here, we assessed genetic polymorphisms in estrogen receptor genes and their association with hypospadias. METHODS: Using a case-control study of 59 cases with hypospadias and 286 controls, we examined the association of hypospadias with the following polymorphisms: PvuII and XbaI in ESR1, and 2681-4A>G in ESR2. RESULTS: For the cases, we found a negative association with the G allele containing variants of ESR1 XbaI (OR = 0.52, P < 0.05), and a negative association with the G allele containing variants of ESR2 2681-4A>G (OR = 0.59, P < 0.05). For the cases, we also identified a negative association with the CG haplotype, and a positive association with the CA haplotype, defined by ESR1 PvuII and XbaI (P < 0.05). CONCLUSIONS: These findings suggest that the G allele containing variants of ESR1 XbaI and the G allele containing variants of ESR2 2681-4A>G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk.