Coffee and metabolic phenotypes: A cross-sectional analysis of the Japan multi-institutional collaborative cohort (J-MICC) study.

BACKGROUND AND AIMS: To date, the relationship between coffee consumption and metabolic phenotypes has hardly been investigated and remains controversial. Therefore, the aim of this cross-sectional study is to examine the associations between coffee consumption and metabolic phenotypes in a Japanese population. METHODS AND RESULTS: We analyzed the data of 26,363 subjects (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Coffee consumption was assessed using a questionnaire. Metabolic Syndrome (MetS) was defined according to the Joint Interim Statement Criteria of 2009, using body mass index (BMI) instead of waist circumference. Subjects stratified by the presence or absence of obesity (normal weight: BMI <25 kg/m2; obesity: BMI ≥25 kg/m2) were classified by the number of MetS components (metabolically healthy: no components; metabolically unhealthy: one or more components) other than BMI. In multiple logistic regression analyses adjusted for sex, age, and other potential confounders, high coffee consumption (≥3 cups/day) was associated with a lower prevalence of MetS and metabolically unhealthy phenotypes both in normal weight (OR 0.83, 95% CI 0.76-0.90) and obese subjects (OR 0.83, 95% CI 0.69-0.99). Filtered/instant coffee consumption was inversely associated with the prevalence of MetS and metabolically unhealthy phenotypes, whereas canned/bottled/packed coffee consumption was not. CONCLUSION: The present results suggest that high coffee consumption, particularly filtered/instant coffee, is inversely associated with the prevalence of metabolically unhealthy phenotypes in both normal weight and obese Japanese adults.

Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Coffee, green tea and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

BACKGROUND: Coffee and green tea, two popular drinks in the Japanese, have recently drawn much attention as potential protective factors against the occurrence of liver cancer. METHODS: We systematically reviewed epidemiologic studies on coffee, green tea and liver cancer among Japanese populations. Original data were obtained by searching the MEDLINE (PubMed) and Ichushi databases, complemented with manual searches. The evaluation was performed in terms of the magnitude of association in each study and the strength of evidence ('convincing', 'probable', 'possible', or 'insufficient'), together with biological plausibility. RESULTS: We identified four cohort and four case-control studies on coffee and liver cancer and six cohort and one case-control studies on green tea and liver cancer. All cohort and case-control studies on coffee reported a weak to strong inverse association, with a summary relative risk (RR) for one cup increase being 0.72 (95% confidence interval [CI] 0.66-0.79). Conversely, all studies but two cohort studies on green tea reported no association, with a corresponding summary RR of 0.99 (95% CI 0.97-1.01, P = 0.37). CONCLUSION: Coffee drinking 'probably' decreases the risk of primary liver cancer among the Japanese population whereas the evidence on an association between green tea and liver cancer is 'insufficient' in this population.

Green tea consumption and mortality in Japanese men and women: a pooled analysis of eight population-based cohort studies in Japan.

The aim of our study was to assess the association between green tea consumption and all-cause and cause-specific mortality in a pooled analysis of eight Japanese population-based cohort studies. Pooled hazard ratios (HR) and 95% confidence intervals (CI), derived from random effects models, were used to evaluate the associations between green tea consumption, based on self-report at baseline, and risk of all-cause and cause-specific mortality. During a mean follow-up of 17.3 years, among 313,381 persons, 52,943 deaths occurred. Compared with individuals who consumed < 1 cup/day, those in the highest consumption category (≥ 5 cups/day) had a decreased risk of all-cause mortality [the multivariate-adjusted HR was 0.90 (95% CI 0.87-0.94) for men and 0.82 (0.74-0.90) for women]. A similar inverse association was observed for heart disease mortality [HR 0.82 (0.75-0.90) for men, and 0.75 (0.68-0.84) for women], and cerebrovascular disease mortality [HR 0.76 (0.68-0.85) for men, and 0.78 (0.68-0.89) for women]. Among women, green tea consumption was associated with decreased risk of total cancer mortality: 0.89 (0.83-0.96) for the 1-2 cups/day category and 0.91 (0.85-0.98) for the 3-4 cups/day category. Results for respiratory disease mortality were [HR 0.75 (0.61-0.94)] among 3-4 cup daily consumers and [HR 0.66 (0.55-0.79)] for ≥ 5 cups/day. Higher consumption of green tea is associated with lower risk for all-cause mortality in Japanese, especially for heart and cerebrovascular disease. Moderate consumption decreased the risk of total cancer and respiratory disease mortality in women.

Coffee consumption and mortality in Japanese men and women: A pooled analysis of eight population-based cohort studies in Japan (Japan Cohort Consortium).

Coffee consumption is increasing globally. We aimed to assess the effect of coffee consumption on the risk of all-cause and cause-specific mortality in a pooled analysis of eight population-based cohort studies in Japan (Japan Cohort Consortium). Data came from eight Japanese cohort studies (144,750 men and 168,631 women). During a mean follow-up time of 17 years, 52,943 deaths occurred. More specifically, 19,495 cancer deaths, 7321 deaths due to heart disease, 6387 cerebrovascular, 3490 respiratory disease and 3382 injuries and accidents. A random effects model was applied to obtain pooled hazard ratios (HRs) and 95% confidence intervals (95%CIs). In both sexes, coffee consumption up to 5 cups/day was overall protective in relation to all-cause mortality, with the association attenuating in the highest category of coffee consumption (≥5 cups/day). In men, a similar inverse association was observed for major causes of mortality except cancer. In women, coffee consumption decreased the risk for mortality due to heart disease in the 1-2 cups/day category, but increased the risk in the ≥5 cups/day category. Coffee consumption was not associated with cancer in both sexes. Results were similar among male current smokers and female never-smokers. Based on available data, this pooled analysis suggests that coffee consumption under five cups per day may be beneficial for reducing the risk of mortality due to major causes.

The Utility of Indigo Carmine and Lipiodol Mixture for Preoperative Pulmonary Nodule Localization before Video-Assisted Thoracic Surgery.

PURPOSE: To evaluate the safety and efficacy of a mixture of indigo carmine and lipiodol (MIL) as a marker of pulmonary nodule before video-assisted thoracic surgery (VATS). MATERIALS AND METHODS: One hundred sixty-eight sessions of pulmonary marking were performed using MIL before VATS for 184 nodules (mean size, 1.2 ± 0.6 cm; range, 0.3-3.6 cm) on 157 patients (83 men and 74 women; median age, 66 years). The mean distance between the lung surface and the nodule was 0.8 ± 0.7 cm (range, 0-3.9 cm). MIL was injected near the nodule using a 23-gauge needle. Mean number of 1.2 ± 0.4 (range, 1-3) punctures were performed in a session for the target nodules, with mean number of 1.1 ± 0.3 (range, 1-3). Successful targeting, localization, and VATS were defined as achievement of lipiodol accumulation at the target site on computed tomography, detection of the nodule in the operative field by fluoroscopy or visualization of dye pigmentation, and complete resection of the target nodule with sufficient margin, respectively. RESULTS: The successful targeting rate was 100%, and the successful localization rate was 99.5%, with dye pigmentation for 160 nodules (87.0%) and intraoperative fluoroscopy for 23 nodules (12.5%). Successful VATS was achieved for 181 nodules (98.4%). Two nodules (1.1%) were not resectable, and surgical margin was positive in 1 nodule (0.5%). Complications requiring interventions occurred in 5 sessions (3.0%) and included pneumothorax with chest tube placement (n = 3) and aspiration (n = 2). No complication related to the injected MIL occurred. CONCLUSIONS: MIL was safe and useful for preoperative pulmonary nodule marking.

Coffee Consumption and All-Cause and Cardiovascular Mortality　- Three-Prefecture Cohort in Japan.

BACKGROUND: Coffee, which contains various bioactive compounds, is one of the most popular beverages. Further accumulation of evidence is needed, however, to confirm whether coffee consumption would be effective in preventing cardiovascular disease in the general Japanese population. Methods and Results: We evaluated the association between coffee consumption frequency (never, sometimes, 1-2 cups/day, 3-4 cups/day and ≥5 cups/day) and mortality from all causes, heart disease, and cerebrovascular disease, in 39,685 men and 43,124 women aged 40-79 years at baseline, in a 3-prefecture cohort study. The coffee consumption frequency was assessed on questionnaire. Cox proportional hazards regression modeling was used to assess the association between coffee consumption frequency and all-cause and cardiovascular disease mortality with adjustment for potential confounders. During 411,341 and 472,433 person-years in men and women, respectively, a total of 7,955 men and 5,725 women died. Coffee consumption frequency was inversely associated with all-cause mortality in both genders (P for trend<0.001). In addition, the risks of mortality from cerebrovascular disease in men (P for trend<0.001), and heart disease in women (P for trend=0.031) were inversely associated with coffee consumption. CONCLUSIONS: In this Japanese population, coffee drinking has a preventive effect on all-cause and on cardiovascular mortality in men and/or women.

Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan.

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person-years, 6,711 incident colorectal cancer cases were identified. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82-1.03 in men and pooled HR 0.90, 95% CI 0.76-1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64-0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.

A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study.

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

Coffee and green tea consumption and subsequent risk of acute myeloid leukemia and myelodysplastic syndromes in Japan.

Although coffee and green tea are suggested to reduce the risk of some types of cancers, only a few epidemiological studies have investigated their effect on the risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here, we investigated the association of coffee and green tea consumption and the risk of AML and MDS in a large-scale population-based cohort study in Japan. A total of 95,807 Japanese subjects (45,937 men and 49,870 women; age 40-69 years at baseline) were followed to the end of 2012, for an average of 18 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between coffee and green tea consumption at baseline and the risk of AML and MDS were assessed using a Cox proportional hazards model with adjustment for potential confounders. During 1,751.956 person-years, we identified 85 AML cases and 70 MDS cases. Our findings showed no significant association between coffee consumption and the risk of AML, or between green tea consumption and the risk of AML or MDS. In contrast, we observed a decreasing dose-response relationship between coffee consumption and the risk of MDS among men (almost none: reference, 1-4 times/week: HR = 0.83, 95% CI: 0.43-1.62; ≥1cups/day: HR = 0.47, 0.22-0.99, p for trend = 0.049). Stratified analysis by smoking status suggested that the observed relative risk for AML and MDS of coffee drinkers relative to non-coffee drinkers might be due to residual confounding by smoking. These findings deserve further investigation in future studies.

Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study.

Background: The aim of this study was to investigate the association of coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan.Methods: In this analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their coffee and green tea consumption were followed up until December 31, 2012, for an average of 18 years. HRs and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders as a measure of association between the risk of malignant lymphoma and multiple myeloma associated with coffee and green tea consumption at baseline.Results: During the follow-up period, a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Overall, our findings showed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma for both sexes.Conclusions: In this study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma.Impact: Our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers Prev; 26(8); 1352-6. ©2017 AACR.

Coffee consumption and the risk of colorectal cancer by anatomical subsite in Japan: Results from the HERPACC studies.

Consumption of coffee, a popular beverage worldwide, has been associated with lower colorectal cancer (CRC) risk. Although CRC exhibits different biological characteristics by anatomical subsite, the possibly heterogeneous impact of coffee on CRC by anatomical subsite has remained unclear. Here, we conducted two case-control studies to examine the association between coffee consumption and CRC risk as well as risk by anatomic subsite among Japanese using data from the Hospital-based Epidemiological Research Program at Aichi Cancer Center I and II (HERPACC-I and II). Subjects were enrolled in HERPACC-I between 1988 and 2000 and in HERPACC-II between 2001 and 2005. Coffee consumption was measured with a self-administered questionnaire. A conditional logistic regression model was used to calculate odds ratios (ORs) of CRC with coffee consumption, adjusted for potential confounders of age, smoking, alcohol drinking, red meat intake, BMI, exercise, family history of CRC, and diabetes mellitus history. We estimated summary ORs by pooling study-specific ORs with a fixed effects model. In total, 2,696 CRC cases and 13,480 non-cancer outpatients as controls were included. Overall, compared to non-drinkers, ORs of less than 1 cup/day, 1-2 cups/day and 3 or more cups/day for CRC were 0.88 (95% CI: 0.77-1.00), 0.90 (95% CI: 0.80-1.01) and 0.78 (95% CI: 0.65-0.92), respectively (trend-p = 0.009). Subsite-specific analysis revealed a significant inverse linear trend between coffee consumption and distal colon cancer (p-trend = 0.048), and a tendency toward a lower risk of rectal cancer (p-trend = 0.068). These findings suggest that coffee consumption might impact the prevention of CRC, especially distal colon cancer.

Coffee drinking and colorectal cancer risk: an evaluation based on a systematic review and meta-analysis among the Japanese population.

OBJECTIVE: It remains unclear whether coffee drinking is associated with colorectal cancer risk. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population. METHODS: Original data were obtained from MEDLINE searches using PubMed or from searches of the 'Ichushi' database, complemented with manual searches. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility. RESULTS: We identified five cohort studies and nine case-control studies. Of these, one cohort study reported a strong inverse association (in women only), whereas three case-control studies reported a strong inverse association with colon or rectal cancer. In meta-analysis, high consumption of coffee was not appreciably associated with colorectal cancer risk among cohort studies, whereas it was associated with significantly lower risk of colorectal or colon cancer among case-control studies. The summary relative risk/odds ratio (95% confidence interval) for the highest versus lowest categories of coffee consumption was 0.95 (0.77-1.17) and 0.78 (0.65-0.95) for cohort and case-control studies, respectively. CONCLUSIONS: The evidence is insufficient to support that coffee drinking increases or decreases the risk of colorectal cancer among the Japanese population.

Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Coffee and green tea consumption is associated with upper aerodigestive tract cancer in Japan.

The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case-control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self-administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk.

Green tea consumption and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

OBJECTIVE: Numerous in vitro and animal studies have shown that green tea has a protective effect against cancer. However, results from epidemiologic studies are conflicting. We evaluated the association between green tea consumption and risk for gastric cancer risk among the Japanese population based on a systematic review of epidemiologic evidence. METHODS: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biologic plausibility. RESULTS: Eight cohort studies and three case-control studies were identified. Overall, we found no preventive effect on gastric cancer for green tea intake in cohort studies. However, a small, consistent risk reduction limited to women was observed, which was confirmed by pooling data of six cohort studies (hazard ratio = 0.79, 95% confidence interval 0.65-0.96 with ≥5 cups/day of green tea intake). Case-control studies consistently showed a weak inverse association between green tea intake and gastric cancer risk. CONCLUSIONS: We conclude that green tea possibly decreases the risk of gastric cancer in women. However, epidemiologic evidence is still insufficient to demonstrate any association in men.

Lung cancer risk and consumption of vegetables and fruit: an evaluation based on a systematic review of epidemiological evidence from Japan.

OBJECTIVE: Clinical trials of ß-carotene supplementation and recent large-scale prospective studies have called into question the protective effects of vegetable and fruit consumption against lung cancer. To re-assess this issue, we reviewed data from Japanese epidemiological studies. METHODS: Original data were obtained from searches of MEDLINE and the Japana Centra Revuo Medicina (Ichushi) database. The associations were assessed based on their magnitude and the strength of the evidence, together with their biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: We identified six cohort studies and four case-control studies on the consumption of vegetables and/or fruit. We focused on fruit and green-yellow vegetables as food items, as they were included in more of the studies, and insufficient data were available on other types of vegetables. Among the three cohort and two case-control studies that reported on green-yellow vegetables, only one of each study type showed a weak inverse association between lung cancer risk and their consumption. Two of the four cohort studies and one (or possibly two) of the four case-control studies demonstrated a weak inverse correlation between lung cancer risk and fruit consumption. Meta-analysis for fruit consumption revealed a summary relative risk that was significantly smaller than unity. CONCLUSIONS: Our analysis of the Japanese epidemiological data showed that fruit consumption possibly decreased the risk of lung cancer, but found insufficient evidence of a link with vegetable consumption. Further prospective studies should assess the effects of consuming these food groups.

Epidermal growth factor receptor mutation status and adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung.

PURPOSE: Adjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur. PATIENTS AND METHODS: The EGFR mutational status of 187 patients with resected lung adenocarcinomas was determined using a polymerase chain reaction-based assay for EGFR exons 19 and 21; the results were then correlated with the effect of adjuvant uracil-tegafur chemotherapy on survival. The antiproliferative effect of fluorouracil (FU) on adenocarcinoma cell lines with EGFR wild-type or mutant type status was examined by measuring the inhibitory concentrations at 50% (IC(50)s). RESULTS: Among the 187 patients, 68 received uracil-tegafur as adjuvant chemotherapy, and 119 were not treated with any chemotherapeutic agents. EGFR mutations were present in 79 patients (43%). Overall, the adjuvant chemotherapy with uracil-tegafur significantly prolonged survival compared with the control group (hazard ratio = 0.38; P = .005). The survival benefit of adjuvant chemotherapy with uracil-tegafur was also examined after stratifying the patients according to EGFR mutation status. Adjuvant chemotherapy significantly prolonged survival among patients with EGFR wild-type tumors (hazard ratio = 0.34; P = .013) but not among patients with EGFR mutant tumors. In an in vitro experiment, the IC(50)s of EGFR mutant cells to FU were higher than those of wild-type cells, indicating that EGFR wild-type cells are more sensitive to FU than mutant cells. CONCLUSION: EGFR status influenced the effect of adjuvant chemotherapy with uracil-tegafur. Adjuvant chemotherapy could be customized based on EGFR status.

Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese.

Dietary intake of fish rich in n-3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been proposed to decrease cancer risk. In contrast to results from laboratory studies, however, protective effects for breast cancer have proved equivocal in epidemiological studies. In the present case-control study, we examined associations between breast cancer risk and fatty acid compositions in erythrocyte membranes as biomarkers for those intakes. Dietary information and blood samples were collected from 103 incident breast cancer cases and 309 non-cancer controls (matched by age and season) and erythrocyte fatty acids were measured using accelerated solvent extraction and gas-liquid chromatography. Dietary intake of n-3 HUFAs demonstrated a negative association with risk (the highest to the lowest tertile, odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27-0.98; p(trend)<0.05), but there was no association with those of saturated fatty acids (SFAs) and meat. Moreover, risk was inversely associated with erythrocyte compositions of EPA (OR, 0.27; 95% CI, 0.14-0.53; p(trend)<0.0001), DHA (OR, 0.06; 95% CI, 0.02-0.16; p(trend)<0.0001) and n-3 HUFAs (OR, 0.11; 95% CI, 0.05-0.24; p(trend)<0.0001), and positively with that of SFAs (OR, 12.29; 95% CI, 4.94-30.57; p(trend)<0.0001) and the ratio of SFAs/n-3 HUFAs (OR, 14.65; 95% CI, 5.67-37.82; p(trend)<0.0001). In conclusion, we showed that erythrocyte compositions of specific fatty acids derived from fish intake, as biomarkers, are associated with lower risk of breast cancer, but further studies are needed to investigate mechanisms linked to the etiology.

Coffee consumption and the risk of endometrial cancer: Evidence from a case-control study of female hormone-related cancers in Japan.

Coffee has become a popular beverage worldwide. Caffeine, a major ingredient of coffee, has been proposed to have a favorable affect on the modulation of circulating estrogen levels and therefore may be of importance in developments on hormone-related cancers. However, epidemiological evidence is limited and inconsistent. We examined the relationship between intake of coffee and hormone-related cancer risk among Japanese women using data from the hospital-based epidemiological research program at Aichi Cancer Center (HERPACC). In total, 2122 breast, 229 endometrial and 166 ovarian cancer cases were included, and 12 425 women, confirmed as free of cancer, were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A statistically significant inverse association between risk of endometrial cancer and coffee consumption was noted in Japanese women, with no clear association evident for breast and ovarian cancer risk. Compared to non-drinker, the OR of daily drinking of 1-2 cups and 3 or more cups per day for endometrial cancer were 0.64 (95% CI: 0.43-0.94) and 0.41 (95% CI: 0.19-0.87), respectively, and the linear trend was also statistically significant (P < 0.01). However, there was no statistically significant association between caffeine intake and endometrial cancer. In summary, the results of the present study suggest that coffee consumption reduces the risk of endometrial cancer in Japanese subjects. Given the scarcity of studies of coffee intake and endometrial cancer and other hormone-dependent cancer risk, additional investigations are warranted.