Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.

AIMS: Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. METHODS: A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of ＜60 ml/min/1.73 m2. Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. RESULTS: During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. CONCLUSIONS: A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.

The prevalence of current smokers and alcohol drinkers among cancer survivors and subjects with no history of cancer among participants in a community-based cardiometabolic screening program in Miyagi prefecture, Japan: a comparison with nationally representative surveys in other countries.

BACKGROUND: We determined the prevalence of current cigarette smokers and alcohol drinkers among cancer survivors and subjects with no history of cancer in Japan and compared the findings with nationally representative studies in other countries. METHODS: We conducted a cross-sectional study of baseline data from a prospective cohort study. A self-administered questionnaire was surveyed during 2013-2015 with residents aged ≥20 years attending a community-based cardiometabolic screening program in Miyagi prefecture in north-eastern Japan. Subjects with past cancer histories were classified as cancer survivors. Sex-specific, age-standardized prevalence of current smokers, and drinkers were calculated. Age-adjusted prevalence ratios (PRs: the cancer survivors' rate divided by the rate of subjects with no history of cancer) and 95% confidence intervals (CIs) were estimated with log-binomial regressions. RESULTS: 36,786 subjects, including 2760 cancer survivors, responded and provided usable information (58.9% of recruited subjects). For men, the age-standardized prevalence of current smokers and drinkers among survivors was 18.8% and 74.4%, respectively, with an age-adjusted PR (95%CI) of 0.76 (0.66-0.86, p < 0.001) and 0.95 (0.91-0.98, p = 0.002), respectively. For women, the figures were 6.1%, 37.9%, 0.84 (0.67-1.06, p = 0.138) and 0.96 (0.90-1.03, p = 0.313), respectively. The U.S., the U.K, and Australian studies generally showed no substantially lower prevalence of current smokers or drinkers in survivors than in subjects with no history of cancer (PR ≥ 0.75), while Korean studies did (PR < 0.75). CONCLUSIONS: A considerable proportion of Japanese cancer survivors, especially men, remained currently smoking and drinking. Consistent with Western studies, the rates were not substantially lower than those among subjects with no history of cancer.

The Major Source of Antioxidants Intake From Typical Diet Among Rural Farmers in North-eastern Japan in the 1990s.

BACKGROUND: Previous Japanese studies have led to the erroneous conclusion of antioxidant capacity (AOC) intakes of the overall Japanese diet due to limitations in the number and types of food measured, especially in rice and seafood intake. The aims of the study were to construct an AOC database of foods representative of the typical Japanese diet and to clarify the high contributors to AOC intake from the overall diet of the Japanese population. METHODS: Commonly consumed foods were estimated using 3-day dietary records (DRs) over the four seasons among 55 men and 58 women in Japan. To generate an AOC database suitable for the typical Japanese diet, hydrophilic (H-)/lipophilic (L-) oxygen radical absorbance capacity (ORAC) values of foods in each food group were measured via validated methods using the food intake rankings. Subsequently, we estimated the AOC intake and the AOC characteristics of a typical Japanese diet. RESULTS: Of 989 food items consumed by the participants, 189 food items were measured, which covered 78.8% of the total food intake. The most commonly consumed types of antioxidant-containing food were tea, soybean products, coffee, and rice according to H-ORAC, and soybean products, fish and shellfish, vegetables, and algae according to L-ORAC. CONCLUSIONS: The characteristics of high AOC intake in rice and seafood more appropriately reflected the Japanese-style diet. Further studies are expected to clarify the association between food-derived AOC and its role in preventing or ameliorating lifestyle-related diseases.

Cigarette smoking and the risk of head and neck cancer in the Japanese population: a systematic review and meta-analysis.

OBJECTIVE: Although cigarette smoking is a well-established risk factor for head and neck cancer, the impact of smoking on head and neck cancer might vary among geographic areas. To date, however, no systematic review of cigarette smoking and head and neck cancer in the Japanese population has yet appeared. METHODS: We conducted a systematic review of previous epidemiological studies for cigarette smoking and head and neck cancer among Japanese. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was conducted to obtain summary estimates for the overall magnitude of association. RESULTS: We identified five cohort studies and 12 case-control studies. Four of five cohort studies and 11 of 12 case-control studies showed a strong positive association between cigarette smoking and head and neck cancer. Nine of 12 studies indicated a dose-response relationship between cigarette smoking and the risk of head and neck cancer. Meta-analysis of 12 studies indicated that the summary relative risk for ever smokers relative to never smokers was 2.43 (95% confidence interval: 2.09-2.83). Summary relative risks for current and former smokers relative to never smokers were 2.68 (2.08-3.44) and 1.49 (1.05-2.11), respectively. CONCLUSIONS: Cigarette smoking is a convincing risk factor for head and neck cancer in the Japanese population.

Food intake and the risk of endometrial endometrioid adenocarcinoma in Japanese women.

The present study examined the association between food intake and endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control study in Japanese women. One hundred sixty-one cases and 380 controls who completed a questionnaire regarding demographic, lifestyle, and food frequency questionnaire were analyzed. Odds ratio (OR) between selected food intakes and EEA were calculated by logistic regression analysis. After adjustment putative confounding factors, the higher intakes of vegetables [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.26-0.83], peanuts (OR = 0.48, CI = 0.27-0.86), fish (OR = 0.52, CI = 0.29-0.93), boiled egg (OR = 0.24, CI = 0.33-0.92), instant noodles (OR = 1.94, CI = 1.12-3.34), instant food items (OR = 2.21, CI = 1.31-3.74), and deep-fried foods (OR = 2.87, CI = 1.58-5.21) were associated with a risk for EEA. The inverse association with a risk of EEA was also seen in higher intakes (g/1000 kcal) for vegetables (0.45, CI = 0.25-0.81) and fish (0.53, CI = 0.30-0.94) as compare to lower intake. Higher intake of vegetables, peanuts, fish, and boiled egg was associated with a reduced risk for EEA, whereas instant noodles, instant food items, and deep-fried foods was associated with an increased risk for EAA as compared to lower levels of intake.

Evaluation of the prevalence of iodine intakes above the tolerable upper intake level from four 3-day dietary records in a Japanese population.

The Japanese population routinely consumes iodine-rich seaweed, thereby probably making Japan the nation with the highest iodine intake worldwide. The present study aimed to estimate the duration of dietary records (DRs) needed to calculate the usual iodine intake and to ascertain the frequency of iodine intakes above the tolerable upper intake level (UL) in the Dietary Reference Intakes for Japanese. Four 3-d DRs for the 4 seasons within a year were collected for 55 men and 58 women. On the basis of analysis of variance, the total variance in iodine intake was classified into inter-individual and intra-individual components. The frequency of appearance for high iodine intakes was estimated. The most commonly consumed types of iodine-containing food items were seaweed, milk and milk products, fish and shellfish, and tofu. The percentage contribution of intra-individual variance was markedly greater than that of inter-individual variance, and the excessive iodine intake was intermittent rather than continuous. The duration for which dietary records were required to assess the usual intake of iodine within 10% of their true mean was 6,276 d for men and 4,953 d for women. The period that transpired until a value was exceeded once was 6.3 d/occurrence for values above UL (2,200 µg), 8.5 d/occurrence for values above 3,000 µg, 9.8 d/occurrence for values above 4,000 µg, 11.2 d/occurrence for values above 5,000 µg, and 16.7 d/occurrence for values above 10,000 µg. To avoid errors in interpretation, it is inappropriate to assess the habitual nutrient intake of a nutrient that is intermittently consumed at maximal levels. It is important to assess the iodine intake in consideration of the range of the nutrient intake and of the time period in which the upper limit is exceeded.

Vitamin C supplementation in relation to inflammation in individuals with atrophic gastritis: a randomised controlled trial in Japan.

Evidence has shown that both C-reactive protein (CRP) and serum amyloid component A (SAA) are increased in individuals with gastritis and stomach cancer. Controlling the level of these biomarkers by inhibiting the gastric infection with high doses of ascorbic acid may reduce the risk of carcinogenesis. A population-based double-blind randomised controlled trial in a Japanese population with atrophic gastritis in an area of high stomach cancer incidence was conducted between 1995 and 2000. Daily doses of 50 or 500 mg vitamin C were given, and 120 and 124 participants completed the 5-year study, respectively. Although serum ascorbic acid was higher in the high-dosage group (1.73 (SD 0.46) µg/l) than in the low-dosage group (1.49 (SD 0.29) µg/l, P< 0.001), at the end of the study, no significant difference was observed for CRP between the low- and high-dosage groups (0.39 (95 % CI 0.04, 4.19) mg/l and 0.38 (95 % CI 0.03, 4.31) mg/l, respectively; P= 0.63) or for SAA between the low- and high-dosage groups (3.94 (95 % CI 1.04, 14.84) µg/ml and 3.85 (95 % CI 0.99, 14.92) µg/ml, respectively; P= 0.61). Vitamin C supplementation may not have a strong effect on reducing infections in individuals with atrophic gastritis.

Health behaviors as predictors for declines in higher-level functional capacity in older adults: the Ohasama study.

OBJECTIVES: To determine the characteristics of health behaviors related to higher-level functional decline in older community-dwelling adults. DESIGN: Prospective. SETTING: Ohasama Town, Japan. PARTICIPANTS: One thousand fifty residents (mean age: 67.5) free of functional decline at baseline. MEASUREMENTS: Health behaviors including smoking status, alcohol consumption, frequency of exercise, sleep duration, dietary habits (supplement use, breakfast, late-night snacking, eating regularly, and eating out), and self-rated health were obtained from a self-administered questionnaire at baseline. Higher-level functional decline was examined using the subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence. RESULTS: During the 7-year follow-up, 27.5% of eligible participants reported decline in higher-level functional capacity. After adjustment for putative confounding factors, health behaviors that were significant predictors for declines in higher-level functional capacity at the 7-year follow-up were current smoking (odds ratio (OR) = 1.58, 95% confidence interval (CI) = 1.06-2.36), sleep duration of 9 hours or longer (OR = 2.15, 95% CI = 1.49-3.11), and poor self-rated health (OR = 1.93, 95% CI = 1.40-2.67). CONCLUSION: Several modifiable health behaviors contribute to higher-level functional decline.

Red meat intake may increase the risk of colon cancer in Japanese, a population with relatively low red meat consumption.

Asian populations have changed from traditional to Westernized diets, with increased red meat intake. They are suggested to be particularly susceptible to the adverse effects of red meat on the development of colorectal cancers, however, few prospective studies of this putative link have been conducted. We examined associations between the consumption of red and processed meat and the risk of subsite-specific colorectal cancer by gender in a large Japanese cohort. During 1995-1998, a validated food frequency questionnaire was administered to 80,658 men and women aged 45-74 years. During 758,116 person-years of follow-up until the end of 2006, 1,145 cases of colorectal cancer were identified. Higher consumption of red meat was significantly associated with a higher risk of colon cancer among women [multivariate hazard ratios (95%CIs) for the highest versus lowest quintiles (HR): 1.48 (1.01, 2.17; trend p=0.03)], as was higher consumption of total meat among men [HR=1.44 (1.06, 1.98; trend p=0.07)]. By site, these positive associations were found for the risk of proximal colon cancer among women and for distal colon cancer among men. No association was found between the consumption of processed meat and risk of either colon or rectal cancer. In conclusion, red meat intake may modestly increase the risk of colon cancer in middle-aged Japanese, although the highest quintile of red meat consumption could be considered moderate by Western standards.

Socioeconomic status and gastric cancer survival in Japan.

BACKGROUND: Few studies have investigated the association between socioeconomic status and the survival of cancer patients in Japan. METHODS: We examined whether occupation or educational level was associated with the survival of 725 gastric cancer patients who were diagnosed within an ongoing large population-based cohort study. RESULTS: After adjustment for age at diagnosis, and sex, we found that, compared with professionals or office workers, unemployed subjects (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.27-3.92) and manual laborers (HR, 1.68; 95% CI, 1.07-2.62) had an increased risk of gastric cancer death. After further adjustment for the clinical extent of disease, the increased risk disappeared. Educational level was not associated with the risk. CONCLUSIONS: These findings suggest that a disparity in survival by occupation exists among Japanese gastric cancer patients, largely due to a lower proportion of early disease among the unemployed and manual laborers.

Fruits and vegetables in relation to prostate cancer in Japanese men: the Japan Public Health Center-Based Prospective Study.

Although dietary risk factors may differ between localized and advanced prostate cancer, data on associations between the consumption of fruits and vegetables and risk of localized and advanced cancers are limited. We examined associations between fruit and vegetable consumption and risk of prostate cancer in a Japanese population. During 1995-1998, a validated food frequency questionnaire was administered to 43,475 men aged 45-74 yr. During 321,061 person-years of follow-up until the end of 2004, 339 cases of prostate cancer were identified. Consumption of fruits or total vegetables was not associated with a decreased risk of total prostate cancer, with corresponding multivariate hazard ratios of the highest vs. lowest quartiles of 1.09 (95% CI = 0.77-1.53; trend P = 0.39) for fruits and 1.33 (95% CI = 0.93-1.91; trend P = 0.52) for total vegetables. Also, no association was observed for intake of either fruits or vegetables (total or any subtype) with localized or advanced prostate cancer. This prospective cohort study suggests that consumption of fruits or vegetables may not be associated with the risk of either localized or advanced prostate cancer in Japanese men. However, the possibility of confounding by detection bias on the risk of localized cancer could not be totally ruled out.

Consumption of sodium and salted foods in relation to cancer and cardiovascular disease: the Japan Public Health Center-based Prospective Study.

BACKGROUND: Although the influence of salt, per se, on the risk of cancer or cardiovascular disease (CVD) might differ from that of salt-preserved foods, few studies have simultaneously examined the effects of sodium and salted foods on the risk of either cancer or CVD. OBJECTIVE: We simultaneously examined associations between sodium and salted food consumption and the risk of cancer and CVD. DESIGN: During 1995-1998, a validated food-frequency questionnaire was administered to 77,500 men and women aged 45-74 y. During up to 598,763 person-years of follow-up until the end of 2004, 4476 cases of cancer and 2066 cases of CVD were identified. RESULTS: Higher consumption of sodium was associated with a higher risk of CVD but not with the risk of total cancer: multivariate hazard ratios for the highest compared with lowest quintiles of intake were 1.19 (95% CI: 1.01, 1.40; P for trend: 0.06) for CVD and 1.04 (95% CI: 0.93, 1.16; P for trend: 0.63) for total cancer. Higher consumption of salted fish roe was associated with higher risk of total cancer, and higher consumption of cooking and table salt was associated with higher risk of CVD. Similar results were seen for the risk of gastric or colorectal cancer and stroke. CONCLUSIONS: Sodium intake as a whole salt equivalent may not increase the risk of cancer but may increase that of CVD. In contrast, salted food intake may increase the risk of cancer. Our findings support the notion that sodium and salted foods have differential influences on the development of cancer and CVD.

Protective effect of vitamin C on oxidative stress: a randomized controlled trial.

BACKGROUND: Although a number of reports regarding the role of reactive oxygen species (ROS) as the first step in cancer induction exist, few studies have investigated how vitamin C influences ROS in human plasma. AIM OF THE STUDY: Using the ROS assay system, a method recently established by one of the authors, we aimed to evaluate the effect of vitamin C supplementation on serum ROS among subjects diagnosed with chronic gastritis. METHODS: A total of 244 Japanese subjects with atrophic gastritis were randomized to take 5-year supplementation of either 50 mg or 500 mg of vitamin C. RESULTS: The adjusted difference in the changes of total ROS between baseline and after 5-year supplementation was statistically significant between the intervention groups: 2.70 decrease (corresponds to 1.26% decrease) in the high-dose group and 4.16 increase (corresponds to 3.79% increase) in the low-dose group, p for difference = 0.01. CONCLUSION: Vitamin C was suggested to reduce oxidative stress among subjects with atrophic gastritis.

Fruit and vegetable consumption and the risk of hypertension determined by self measurement of blood pressure at home: the Ohasama study.

It is well recognized that high fruit and vegetable consumption is associated with a reduction of blood pressure (BP) measured by conventional BP measurement in Western countries; however, there is little evidence about these associations in other regions and there have been no reports on these associations using self-measured BP at home (home BP). The objective of this work was to investigate the associations of fruit and vegetable consumption and their related micronutrients with the reduction of hypertension risk by using home BP in Japanese residents. Data were obtained from 1,569 residents aged 35 and over who measured their home BP in a general population of Ohasama, Japan. Dietary intake was measured using a 141-item food-frequency questionnaire (FFQ) and then subjects were divided into tertiles according to fruit, vegetable, potassium, vitamin C, and beta-carotene consumption. Hypertension was defined as home systolic/ diastolic BP > or = 135/85 mmHg and/or the use of antihypertensive medication. The prevalence of home hypertension was 39.4% for men and 29.3% for women. After adjustment for all potential confounding factors, the highest-tertile consumptions of fruits, vegetables, potassium, and vitamin C were associated with a significantly lower risk of hypertension (45%, 38%, 46%, and 43% lower risk of home hypertension, respectively). In conclusion, this cross-sectional study based on home BP measurement suggests that high-level consumptions of fruits, vegetables, potassium, and vitamin C are associated with a significantly lower risk of hypertension.

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.

Case-control study of coffee consumption and the risk of endometrial endometrioid adenocarcinoma.

This study examined the association between coffee consumption and the risk of endometrial endometrioid adenocarcinoma (EEA) in Japan by a case-control design. The cases consisted of 107 women less than 80 years of age from two medical centers who had been histopathologically diagnosed to have EEA. The controls, selected from the participants of a cancer-screening program, were 214 women, with two controls selected for each case (matched for age and for area of residence). A self-administered questionnaire containing questions to determine dietary and beverage consumption, as well as reproductive history, was distributed to the cases and controls. Conditional logistic regression analysis was used to estimate the odds ratio (OR) of EEA for three levels of coffee consumption with adjustment for potential confounding factors. The multivariate-adjusted OR of EEA for individuals in the highest tertile of coffee consumption (2 to 3 cups or more/day) was 0.4 [95% confidence interval (CI), 0.2-0.9], and that of cases in the intermediate tertile (5 to 6 times/week-1 cup/day) was 0.6 (95% CI, 0.3-1.2), relative to the individuals in the lowest tertile of coffee consumption (3 to 4 times or less/week) (P for trend=0.014). The above association was observed in postmenopausal women (P for trend=0.016), but not in premenopausal women (P for trend=0.90). This study thus revealed an inverse dose-response relationship between coffee consumption and the risk of EEA, and its strong association in postmenopausal women but not in premenopausal women.

Fruit and vegetable intake and risk of total cancer and cardiovascular disease: Japan Public Health Center-Based Prospective Study.

Few studies have investigated the effects of fruit and vegetables on the risk of both cancer and cardiovascular disease (CVD). The authors examined associations between fruit and vegetable consumption and risk of total cancer and CVD in the same Japanese population. During 1995-1998, a validated food frequency questionnaire was administered in nine areas to 77,891 men and women aged 45-74 years. During as many as 459,320 person-years of follow-up until the end of 2002, 3,230 cancer cases and 1,386 CVD cases were identified. Higher consumption of fruit, but not vegetables, was associated with significantly lower risk of CVD: multivariate hazard ratios for the highest versus lowest quartiles of intake were 0.81 (95% confidence interval (CI): 0.67, 0.97; trend p = 0.01) for fruit and 0.97 (95% CI: 0.82, 1.15; trend p = 0.66) for vegetables. Consumption of fruit or vegetables was not associated with decreased risk of total cancer: corresponding hazard ratios were 1.02 (95% CI: 0.90, 1.14; trend p = 0.95) for fruit and 0.94 (95% CI: 0.84, 1.05; trend p = 0.16) for vegetables. This prospective cohort study demonstrated that, in the Japanese population, consumption of fruit is associated with lower risk of CVD, whereas fruit or vegetables may not be associated with lower risk of total cancer.

Time spent walking and risk of colorectal cancer in Japan: the Miyagi Cohort study.

Higher levels of physical activity have been consistently associated with a lower risk of colon cancer in earlier epidemiological studies. The specific benefits of walking, however, remain relatively unexplored. In 1990, 20 519 men and 21 469 women in Japan completed a self-administered questionnaire including a question on time spent walking per day. During 7 years of follow-up, 260 cases of colorectal cancer were documented in 305 790 person-years. We used the Cox proportional hazards regression model to estimate the relative risk of incident cancer (colorectal, colon, and rectal) according to three levels of walking. Time spent walking was inversely associated with risk of colorectal cancer incidence in men. Compared with men who walked 0.5 h or less per day, the multivariate relative risks were 1.06 (95% confidence interval 0.72-1.57) for men who walked between 0.5 and 1 h per day, and 0.57 (95% confidence interval 0.38-0.83) for men who walked 1 h or more per day (P for trend=0.003). Time spent walking per day was associated with a lower risk of colon cancer in Japanese men but not in women, and there was no association between time spent walking and the risk of rectal cancer.

Effects of monotherapy of temocapril or candesartan with dose increments or combination therapy with both drugs on the suppression of diabetic nephropathy.

We examined the effects of increasing the recommended initial doses of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), or of switching to combination therapy with both drugs, on diabetic nephropathy. Hypertensive type 2 diabetic patients with urinary albumin excretion (ACR) between 100 and 300 mg/g creatinine (Cre) were assigned to the following five groups in which an antihypertensive drug was administered at a recommended initial dose for 48 weeks, and then either the dose was doubled or an additional drugs was added to regimen for the following 48 weeks: N, nifedipine-CR (N) 20 mg/day (initial dose); T, ACEI temocapril (T) 2 mg/day; C, ARB candesartan (C) 4 mg/day; T+C, T first and then addition of C; C+T, C first and then addition of C. ACR decreased in the T (n=34), C (n=40), T+C (n=37) and C+T (n=35) groups, but not in the N group (n=18). However, the anti-proteinuric effect was less in the T than in the C, T+C or C+T groups, while no differences existed among the latter three. In each group, there were significant linear relationships between attained BP and ACR; however, the regression lines were shifted toward lower ACR level in the renin-angiotensin system-inhibition groups compared with the N group. These results indicate that an ACEI and/or ARB is superior to a CCB in retarding diabetic nephropathy, while the combination of low doses of ACEI and ARB has effects similar to those of high-dose ARB. Even among patients treated with an ACEI and/or ARB, lowering BP is important.

Cigarette smoking and the risk of colorectal cancer among men: a prospective study in Japan.

The association between cigarette smoking and the risk of colorectal cancer remains controversial. We examined this association using a population-based prospective cohort study in Miyagi, Japan. In 1990, we delivered a self-administered questionnaire on cigarette smoking and other health habits to 25 279 men who were 40-64 years of age and lived in 14 municipalities of Miyagi Prefecture. A total of 22 836 men responded (90.3% response rate). During 7 years of follow-up (158 376 person-years), we identified 188 patients of colorectal cancer. Relative risks and 95% confidence intervals were estimated by the Cox proportional-hazards regression analysis with adjustment for potential confounders. The multivariate-adjusted relative risks (95% confidence interval) of colorectal cancer for past smokers and current smokers compared with those who had never smoked were 1.73 (1.04-2.87) and 1.47 (0.93-2.34), respectively. Among current smokers, both a higher number of cigarettes smoked per day and an earlier age at which smoking had started were associated with a significant linear increase in risk (P for trend <0.05). Our findings are consistent with the hypothesis that cigarette smoking is associated with a higher risk of colorectal cancer in men.