Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Dietary melatonin and liver cancer incidence in Japan: From the Takayama study.

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.

Body mass index and lung cancer risk: Pooled analysis of 10 prospective cohort studies in Japan.

Mounting evidence suggests that body mass index (BMI) is inversely associated with the risk of lung cancer. However, relatively few studies have explored this association in Asian people, who have a much lower prevalence of obesity than Caucasians. We pooled data from 10 prospective cohort studies involving 444,143 Japanese men and women to address the association between BMI and the risk of lung cancer. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in each cohort using the Cox proportional hazards model. A meta-analysis was undertaken by combining the results from each cohort. Heterogeneity across studies was evaluated using Cochran's Q and I2statistics. During 5,730,013 person-years of follow-up, 6454 incident lung cancer cases (4727 men and 1727 women) were identified. Baseline BMI was inversely associated with lung cancer risk in men and women combined. While leanness (BMI <18.5) was associated with a higher risk of lung cancer (HR 1.35; 95% CI, 1.16-1.57), overweight and obesity were associated with a lower risk, with HRs of 0.77 (95% CI, 0.71-0.84) and 0.69 (95% CI, 0.45-1.07), respectively. Every 5 kg/m2 increase in BMI was associated with a 21% lower risk of lung cancer (HR 0.79; 95% CI, 0.75-0.83; p < 0.0001). Our pooled analysis indicated that BMI is inversely associated with the risk of lung cancer in the Japanese population. This inverse association could be partly attributed to residual confounding by smoking, as it was more pronounced among male smokers.

Dietary polyamine intake and all-cause and cause-specific mortality in Japanese adults in the Takayama study.

Epidemiological studies on the potential health effects of dietary polyamines are scarce. The present study aimed to estimate habitual intake of polyamines (putrescine, spermidine and spermine) and examine whether spermidine intake is inversely associated with all-cause and cause-specific mortality in a population-based cohort study in Japan. The study included 13 355 men and 15 724 women aged 35 years and older. Diet was assessed via a validated FFQ at the baseline in 1992. The intake of polyamines was estimated mainly using databases of polyamine content in foods consumed among Japanese population. Sex-specific hazard ratios (HR) and 95 % CI for all-cause and cause-specific mortality were estimated according to polyamine quartiles. During 16 years of follow-up, 2901 deaths in men and 2438 in women occurred. The intake of any polyamine was not significantly associated with all-cause or cause-specific mortality after controlling for covariates in men and women. There was a suggestive positive association between spermidine intake and cancer mortality in women: HR for the highest v. lowest quartile were 1·38 (95 % CI (0·99, 1·93); Ptrend = 0·02). Our results did not provide support for the notion that dietary spermidine has beneficial effects on mortality. Further studies on dietary polyamines and longevity, as well as the morbidity of specific diseases, including cancer, are needed across populations with different dietary habits.

Real-world utilization of lenvatinib and pembrolizumab combination therapy for the treatment of endometrial cancer in the USA.

Aim: Describe treatment and dosing patterns of lenvatinib and pembrolizumab combination therapy (lenva+pembro) among endometrial cancer (EC) patients in US clinical practice. Materials & methods: Retrospective cohort study among adults with EC initiating lenva+pembro in second line (2L) or third line and later (≥3L) between 17 September 2019 and 30 June 2021. Results: 110 patients initiated lenva+pembro in 2L and 135 patients in ≥3L. Majority of patients initiated lenva+pembro at label-recommended starting doses/interval. Less than half changed lenvatinib dose over time. At median follow-up of 7.3 and 8.7 months, median (95% CI) duration of therapy was 5.1 (4.7-6.1) and 5.8 (4.2-7.3) months for patients in 2L and ≥3L, respectively. Conclusion: Lenva+pembro was mostly initiated at label-recommended dose.

This study looked at details of lenvatinib and pembrolizumab combination treatment among patients with endometrial cancer (EC) in the USA. Specifically, these patients had received prior chemotherapy or hormone therapy before starting lenvatinib and pembrolizumab. Most patients started lenvatinib and pembrolizumab at the dose recommended by the product label and received the next pembrolizumab injection within the recommended timeframe. Over time, more than half of the patients did not change the dose of lenvatinib, and most patients had the same dose of pembrolizumab. On average, patients were treated with lenvatinib and pembrolizumab for 5­6 months. This study showed that in general, patients were taking lenvatinib and pembrolizumab for treatment of EC as recommended by product labels.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

BACKGROUND: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. METHODS: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. RESULTS: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. CONCLUSION: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Body mass index and esophageal and gastric cancer: A pooled analysis of 10 population-based cohort studies in Japan.

The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population-based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person-years of follow-up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5-kg/m2 increase 0.57, 95% CI 0.50-0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00-1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m2 ) relative to BMI <25 kg/m2 was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80-2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05-1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study-the largest in an Asian country-provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype- or subsite-specific carcinogenic impact of BMI in a Japanese population.

Cigarette Smoking, Smoking Cessation, and Bladder Cancer Risk: A Pooled Analysis of 10 Cohort Studies in Japan.

BACKGROUND: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. METHODS: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. RESULTS: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18-1.82) and current smokers (HR 1.96; 95% CI, 1.62-2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67-3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97-1.63). CONCLUSION: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.

Association of dietary fibre intake with subsequent fasting glucose levels and indicators of adiposity in school-age Japanese children.

OBJECTIVE: To evaluate the relationships of fibre intake with subsequent BMI sd-score, waist-to-height ratio and serum fasting glucose levels among school-age Japanese children. DESIGN: This is a prospective study of school-age Japanese children. Participants were followed from 6-7 to 9-10 years of age (follow-up rate: 92·0 %). Fibre intake was assessed using a validated FFQ. Serum fasting glucose was measured by a hexokinase enzymatic method. Using a general linear model, the associations between dietary fibre intake at baseline and BMI sd-score, waist-to-height ratio, and serum levels of fasting glucose at follow-up were evaluated after considering potential confounding factors. SETTING: Public elementary schools in a city in Japan. PARTICIPANTS: A total of 2784 students. RESULTS: The estimated means for fasting glucose at 9-10 years of age were 86·45, 85·68, 85·88 and 85·58 mg/dl in the lowest, second, third and highest quartile of fibre intake at 6-7 years of age, respectively (P = 0·033, trend P = 0·018). Higher fibre intake at 6-7 years of age was associated with lower waist-to-height ratio at 9-10 years of age (trend P = 0·023). The change in fibre intake was inversely associated with concurrent change of BMI sd-score (trend P = 0·044). CONCLUSION: These results suggest that dietary fibre intake may be potentially effective to limit excess weight gain and lower glucose levels during childhood.

Sleep-related factors and circulating levels of sex hormones in premenopausal Japanese women.

Sleep disruption and circadian disruption have been proposed to be risk factors of breast cancer. The present study examined the associations of sleep-related factors, referring to night shift work, sleep habits, and sleep disturbances, with the plasma levels of sex hormones in premenopausal Japanese women. Study participants were 432 women who had regular menstrual cycles less than 40 days long. Information on their history of night shift work and sleep disturbances was obtained using a self-administered questionnaire. Information on their sleep habits, such as usual wake-up times, bedtimes, and ambient light level while sleeping, was obtained in an interview. The participants' height and weight were measured. Plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), FSH, and LH were also measured. After controlling for the phase of the menstrual cycle and other covariates, more years of night shift work ≥ once a week during the past 10 years was significantly associated with a lower SHBG and a higher free estradiol level. Shorter sleep duration was significantly associated with the higher total, bioavailable, and free testosterone levels. Sleep disturbance by awaking after sleep onset was significantly associated with a high free estradiol level. The data suggest that long-term night shift work, short sleep duration, and arousal during sleep are associated with higher estradiol or testosterone levels in premenopausal women.

Associations of the timing of sleep and meals with the presence of gastroesophageal reflux disease in community-dwelling women in Japan.

BACKGROUND: It has been suspected that circadian rhythms may play a part in the pathogenesis of gastrointestinal diseases including gastroesophageal reflux disease (GERD). The present study aimed to examine the cross-sectional association of the timing of sleep and meals with the presence of GERD in community-dwelling women in Japan. METHODS: In total, 605 women responded to a self-administered questionnaire asking for information on GERD symptoms, sleep habits, sleep disturbances and the timing of meals. GERD symptoms were evaluated using the Frequency Scale for the Symptoms of GERD, and participants with a score of more than seven points were classified as having GERD. RESULTS: In total, 104 (17.2%) women were found to have GERD. Later bedtime on both weekdays and weekends and later midpoint of sleep were significantly associated with the odds ratios (OR) of GERD after controlling for covariates: ORs for each 1 h delay were 1.31 (95% confidence interval [CI] = 1.03-1.68), 1.38 (95% CI = 1.08-1.75) and 1.43 (95% CI = 1.06-1.95). Having lunch at irregular times was significantly associated with the increased OR of GERD (1.99; 95% CI = 1.02-3.91). Longer overnight fasting duration and longer time intervals from the midpoint of sleep to breakfast and lunch were significantly associated with decreased OR of GERD (ORs for each 1 h increase were 0.73 [95% CI = 0.56-0.95], 0.64 [95% CI = 0.46-0.88] and 0.70 [95% CI = 0.51-0.96]). CONCLUSIONS: These data suggest that the timing of sleep and timing of meals relative to the sleep/wake cycle are associated with the presence of GERD.

Sleep duration and risk of cancer incidence and mortality: A pooled analysis of six population-based cohorts in Japan.

Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population-based cohorts with 271 694 participants. During a total follow-up period of about 5.9 million person-years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random-effects meta-analysis. Sleep duration of ≥10 hours (vs 7 hours) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02-1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00-1.39) and women (HR 1.44, 95% CI 1.20-1.73). Sleep duration of ≤5 hours (vs 7 hours) was not associated with cancer incidence and mortality. However, among postmenopausal women, sleep durations of both ≤5 and ≥10 hours (vs 7 hours) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥10 hours is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men.

Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study.

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site-specific cancers in a population-based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE Nε -carboxymethyl-lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries. During a mean follow-up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92-3.10), 1.48 (95% CI: 0.77-2.84), and 2.10 (95% CI: 1.10-3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study.

Altered white matter microstructure and neurocognitive function of HIV-infected patients with low nadir CD4.

Altered white matter microstructure has been reported repeatedly using diffusion tensor imaging (DTI) in HIV-associated neurocognitive disorders. However, the associations between neurocognitive deficits and impaired white matter remains obscure due to frequent physical and psychiatric comorbidities in the patients. Severe immune suppression, reflected by low nadir CD4 T-cell counts, is reported to be associated with the neurocognitive deficits in the patients. In the present study, we examined white matter integrity using DTI and tract-based spatial statistics (TBSS), and neurocognitive functions using a battery of tests, in 15 HIV-infected patients with low nadir CD4, 16 HIV-infected patients with high nadir CD4, and 33 age- and sex-matched healthy controls. As DTI measures, we analyzed fractional anisotropy (FA) and mean diffusivity (MD). In addition, we investigated the correlation between white matter impairments and neurocognitive deficits. Among the three participant groups, the patients with low nadir CD4 showed significantly lower performance in processing speed and motor skills, and had significantly increased MD in widespread regions of white matter in both hemispheres. In the patients with low nadir CD4, there was a significant negative correlation between motor skills and MD in the right motor tracts, as well as in the corpus callosum. In summary, this study may provide white matter correlates of neurocognitive deficits in HIV-infected patients with past severe immune suppression as legacy effects.

Dietary lactose and galactose intakes are associated with a later onset of natural menopause among women in a Japanese community.

Galactose and its metabolites, primarily derived from lactose, may have toxic effects on the ovary. We aimed to prospectively examine the associations of galactose and lactose intakes with the onset of natural menopause. The data of a population-based cohort study in a Japanese community (the Takayama study) initiated in 1992 were analysed, with follow-up data collected in 2002. Among the participants of the Takayama study, premenopausal women (n 3115) aged 35-56 years at baseline were included in this study. Dietary intake, including lactose and galactose was assessed only at baseline using a FFQ. The menopausal status and age at menopause were determined based on the participants' self-reports, and natural menopause was defined as the absence of menstruation for 12 months or more. Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95 % CI. A total of 1790 women experienced natural menopause within the 10-year follow-up. Lactose and galactose intakes were associated with a later onset of natural menopause after adjusting for potential confounding factors and the HR (95 % CI) for the highest v. lowest quartile were 0·80 (0·69, 0·92) (P-trend = 0·001) in lactose and 0·86 (0·74, 1·00) in galactose (P-trend = 0·036), respectively. High intakes of lactose and galactose were associated with a later onset of natural menopause. Despite the presumed ovotoxicity effects, lactose and galactose intakes at usual levels may not be deleterious to the ovarian aging process among Japanese community-dwelling women.

Associations of total nut and peanut intakes with all-cause and cause-specific mortality in a Japanese community: the Takayama study.

Numerous epidemiological studies have suggested that nut intake is associated with a reduced risk of mortality. Although diets and lifestyles differ by regions or races/ethnicities, few studies have investigated the associations among non-white, non-Western populations. We evaluated the associations of total nut and peanut intakes with all-cause and cause-specific mortality in a population-based prospective cohort in Japan. Participants (age: ≥35 years at baseline in 1992; n 31 552) were followed up until death or the end of follow-up in 2008. Those with cancer, CHD or stroke at baseline were excluded. Dietary intake was assessed only at baseline by using a validated FFQ. In total, 2901 men died during 183 299 person-years and 2438 women died during 227 054 person-years. The mean intakes of total nuts were 1·8 and 1·4 g/d in men and women, respectively. Although peanut intake accounted for approximately 80 % of the total nut intake, total nut and peanut intakes were inversely associated with all-cause mortality in men after adjusting for all potential confounders. For example, compared with the lowest quartile category, the adjusted hazard ratio (95 % CI) of total nut intake for all-cause mortality in men of the highest quartile category was 0·85 (95 % CI 0·75, 0·96) (Pfor trend = 0·034). Peanut intake was inversely associated with digestive disease mortality in men and CVD mortality in women. Total nut and peanut intakes, even in low amounts, were associated with a reduced risk of mortality particularly in men.

Adult height in relation to the risk of colorectal cancer among the Japanese population: an evaluation based on systematic review and meta-analysis.

OBJECTIVE: The association between adult-attained height and risk of colorectal cancer remains elusive among the Japanese population. We performed a systematic review and meta-analysis of epidemiological studies in Japan. METHODS: We systematically searched the MEDLINE (PubMed) and Ichushi databases and complemented it with manual search to identify eligible studies. We extracted relative risks or odds ratios from the selected studies and conducted meta-analysis to estimate the summary relative risk with 95% confidence interval. We made the final judgment based on a consensus of the research group members considering both epidemiological evidence and biological plausibility. RESULTS: This systematic review identified four cohort and one case-control studies among the Japanese. The meta-analysis of these five studies showed the summary relative risk of 1.21 (95% confidence interval: 1.07-1.35) of overall colorectal cancer for the highest vs. lowest categories of height. In the analysis by the cancer subsite, the association was significant for colon cancer with a summary relative risk of 1.26 (95% confidence interval: 1.10-1.45) but not for rectal cancer 1.05 (95% confidence interval: 0.71-1.54). In the analysis by sex, tall stature was associated with a significantly increased risk of overall colorectal cancer in both sexes; the summary relative risk was 1.21 (95% confidence interval: 1.04-1.41) in men and 1.20 (95% confidence interval: 1.00-1.44) in women, respectively. CONCLUSIONS: The evidence to support that adult-attained height is associated with increased risk of colorectal cancer (colon cancer) among the Japanese population is 'probable'.