Plasma vitamin D and risk of colorectal cancer: the Japan Public Health Center-Based Prospective Study

We investigated the association between plasma 25(OH)D and the subsequent colorectal cancer incidence risk by a nested case-control study in The Japan Public Health Center-based Prospective Study, covering 375 newly diagnosed cases of colorectal cancer from 38 373 study subjects during a 11.5-year follow-up after blood collection. Two controls were matched per case on sex, age, study area, date of blood draw, and fasting time. In a conditional logistic regression model with matched pairs adjusted for smoking, alcohol consumption, body mass index, physical exercise, vitamin supplement use, and family history of colorectal cancer, plasma 25(OH)D was not significantly associated with colorectal cancer in men or in women. However, the lowest category of plasma 25(OH)D was associated with an elevated risk of rectal cancer in both men (odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0-20) and women (OR, 2.7, 95% CI, 0.94-7.6), compared with the combined category of the other quartiles. Our results suggest that a low level of plasma 25(OH)D may increase the risk of rectal cancer.     

Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite-related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome P450 2E1 in the Japanese population

BACKGROUND: It is believed that acetaldehyde plays an important role in alcohol-related carcinogenesis; although current epidemiologic studies have provided inconsistent findings on the association between alcohol consumption and the risk of lung cancer. METHODS: To clarify the hypothesis that genetic polymorphisms in alcohol-metabolizing enzymes may influence susceptibility to lung cancer, the authors conducted a hospital-based case-control study and examined genetic polymorphisms in the alcohol dehydrogenase 3, aldehyde dehydrogenase 2 (ALDH(2)), and cytochrome P450 2E1 genes in 505 patients with histologically confirmed lung cancer and in a group of 256 noncancer controls who provided complete cigarette and alcohol consumption histories. Genotyping was conducted by polymerase chain reaction-restriction fragment-length polymorphism assay. RESULTS: A significant association was noted between alcohol consumption and lung cancer risk. Thus, using the median value for the controls as the cut-off point, the odds ratios (OR) for light and heavy drinkers were 1.76 and 1.95, respectively (P for trend = .012), compared with nondrinkers. In addition, there was a significant trend toward increased risk of lung cancer in drinkers with ALDH(2) variant alleles (P for trend <.0001). The adjusted OR for heavy drinkers was 6.15 compared with nondrinkers. Regarding associations between histologic type and genotypes, the ALDH(2) variant allele was significantly less common in patients who had adenocarcinoma compared with controls. CONCLUSIONS: The current observations suggested a positive association between alcohol consumption and the risk of lung cancer: Drinking may increase the risk, especially among individuals who have the variant ALDH(2) alleles.     

Tumor suppressor 101F6 and ascorbate synergistically and selectively inhibit non-small cell lung cancer growth by caspase-independent apoptosis and autophagy

101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector-mediated gene transfer significantly inhibited tumor cell growth in 3p21.3-deficient non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The molecular mechanism of 101F6-mediated tumor suppression is largely unknown. A computer-aided structural and functional model predicts the 101F6 protein to be a member of the cytochrome b561 protein family that is involved in the regeneration of the antioxidant ascorbate. 101F6 protein is expressed in normal lung bronchial epithelial cells and fibroblasts but is lost in most lung cancers. Treatment with 101F6 nanoparticle-mediated gene transfer in combination with a subpharmacologic dose (200-500 micromol/L) of ascorbate synergistically and selectively inhibited lung cancer cell growth in vitro. Systemic injection of 101F6 nanoparticles plus the i.p. injection of ascorbate synergistically inhibited both tumor formation and growth in human NSCLC H322 orthotopic lung cancer mouse models (P<0.001). Furthermore, exogenous expression of 101F6 enhanced intracellular uptake of ascorbate, leading to an accumulation of cytotoxic H(2)O(2) and a synergistic killing of tumor cells through caspase-independent apoptotic and autophagic pathways. The antitumor synergism showed by the combination treatment with systemic administration of 101F6 nanoparticles and ascorbate on lung cancer offers an attractive therapeutic strategy for future clinical trials in cancer prevention and treatment.     

Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists,neurologists and dermatologists

Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the physician's specialty. The aim of the present study was to establish the treatment consensus among specialists of the three fields to standardize the patient care. We formed a research team supported by a grant from the Ministry of Health, Labor and Welfare, Japan. Clinical questions (CQ) on the management of PM and DM were raised. A published work search on CQ was performed primarily using PubMed. Using the nominal group technique, qualified studies and results in the published work were evaluated and discussed to reach consensus recommendations. They were sent out to the Japan College of Rheumatology, Japanese Society of Neurology and Japanese Dermatological Association for their approval. We reached a consensus in 23 CQ and made recommendations and a decision tree for management was proposed. They were officially approved by the three scientific societies. In conclusion, a multidisciplinary treatment consensus for the management of PM and DM was established for the first time.     

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.     

Cigarette smoking,alcohol consumption and subsequent gastric cancer risk by subsite and histologic type

The effect of cigarette smoking or alcohol consumption on the risk of gastric cancer has not been clarified. We investigated this relationship, considering the anatomic subsite and histologic type of gastric cancer. A total of 19,657 men (aged 40-59 years at baseline), who responded to the baseline questionnaire and reported no serious illness at that time, were followed for 10 years, from January 1990 to December 1999. Gastric cancer was confirmed histologically in 293 men. Smoking was associated with an increased risk of the differentiated type of distal gastric cancer; compared to the group who never smoked, the adjusted rate ratios (RRs) of gastric cancer for past and current smokers were 2.0 (95% CI 1.1-3.7) and 2.1 (95% CI 1.2-3.6), respectively. No association was observed between cigarette smoking and risk of the undifferentiated type of distal gastric cancer except for a suggestive association with cardia cancer. For alcohol consumption, elevated risk was suggested only for cardia cancer of all histologic types, though the relationship failed to reach significance. Among those who drank alcohol at least once per week, RRs for ethanol intake of 2.7-161.0, 162.0-322.0 and 322.5+ g/week compared to those who drank 0-3 times/month were 2.5 (95% CI 0.7-9.5), 3.3 (0.9-11.6) and 3.0 (0.8-11.1), respectively (p(trend) = 0.66). In conclusion, our results confirm that smoking is related to gastric cancer of the differentiated type. Further studies with more cases are needed to detect a positive association between cigarette smoking or alcohol consumption and cardia cancer.     

Development of substituted fatty acid food composition table for the use in nutritional epidemiologic studies for Japanese populations: its methodological backgrounds and the evaluation.

Results of dietary assessment are influenced by quality of food composition tables used for nutrient calculation. The Japanese food composition table has considerable missing values for fatty acid compositions. Substitution is often used for filling missing values. We examined reliability of the following 4 major substitution methods using available values of arbitrarily selected 83 sets of foods from the published fatty acid composition table of Japanese foods: by a different part of the same specie, by a similar specie, by a same specie in the United States' Department of Agriculture food composition table, and by recipe. The mean correlation coefficients of food pairs were 0.97, 0.96, 0.84, and 0.80 respectively. Next, we substituted fatty acid compositions for the 794 missing foods using the 4 substitution methods, and developed the table with 1245 foods including those listed in the original (non-substituted) fatty acid composition table. Lastly, we calculated fatty acid intake levels with the original (non-substituted) and the developed (substituted) tables using 28- or 14-day dietary records of 211 men and women as a sample data, and compared the results. The intakes of all five fatty acid groups increased. The increase was most marked in saturated fatty acids (26% in men and 31% in women in crude values). As a consequence, polyunsaturated to saturated fatty acid ratio decreased from 1.15 to 1.01 in men and from 1.13 to 0.96 in women. The use of the developed fatty acid food composition table may increase the reliability on nutrition-disease association in future nutritional epidemiologic studies for Japanese populations.     

Descriptive Epidemiology of Diabetes Prevalence and HbA1c Distributions Based on a Self-Reported Questionnaire and a Health Checkup in the JPHC Diabetes Study

Background

The present study examined the prevalence of diabetes in Japan during the late 1990s and early 2000s using the Japan Public Health Center-based Prospective Diabetes cohort. We also investigated the distributions of HbA1c values in noncompliant diabetic participants in the cohort.

Methods

A total of 28 183 registered inhabitants aged 46–75 years from 10 public health center areas were included in the initial survey. The 5-year follow-up survey included 20 129 participants. The prevalence of diabetes was estimated using both a self-reported questionnaire and laboratory measurements. Among the participants who reported the presence of diabetes on the questionnaire (self-reported diabetes), the distributions of HbA1c values were described according to their treatment status.

Results

The age-standardized prevalence of diabetes in 55- to 74-year-old adults was 8.2% at the initial survey and 10.6% at the 5-year follow-up. At the initial survey, among participants with self-reported diabetes, the mean HbA1c values in the participants who had never and who had previously received diabetes treatment were 7.01% (standard deviation [SD] 1.56%) and 6.56% (SD 1.46%), respectively. Approximately 15% of the participants who had self-reported diabetes but had never received diabetes treatment had an HbA1c ≥ 8.4%.

Conclusions

The prevalence of diabetes increased in the JPHC cohort between the late 1990s and early 2000s. A certain proportion of participants who were aware of their diabetes but were not currently receiving treatment had poor diabetic control. Efforts to promote continuous medical attendance for diabetes care may be necessary.Key words: diabetes mellitus, prevalence, self-report, HbA1c