Roles of the ALDH2 and ADH1B genotypes on the association between alcohol intake and serum adiponectin levels among Japanese male workers.

BACKGROUND: Adiponectin secreted from adipose tissue is assumed to mediate protective effects on development of metabolic syndrome (MetS) and MetS-related diseases such as cardiovascular diseases and cancer. Relationship between alcohol intake and circulating adiponectin levels is not consistent among the several previous studies. In the present study, we investigated effects of alcohol intake and the alcohol-related polymorphisms on serum adiponectin levels among Japanese male workers. METHODS: We conducted a cross-sectional design study with 541 male workers aged 51.5 ± 5.9 (mean ± SD) years in a Japanese plant. Information on alcohol intake and other lifestyles was obtained by a self-administered questionnaire. Serum total adiponectin (T-Ad), high-molecular-weight adiponectin (HMW-Ad), medium-molecular-weight adiponectin (MMW-Ad), and low-molecular-weight adiponectin (LMW-Ad) levels were measured by the enzyme-linked immune assay system kit. Two genotypes in the alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes were determined using blood sample. In multivariate regression analyses, we adjusted for age, body mass index, smoking, and physical exercise. RESULTS: Among all subjects, high alcohol consumption of 12 units (1 unit contains 22.9 g of ethanol) a week or more was negatively associated with T-Ad levels in the multivariate model, although not significant. When we performed analyses separately for each genotype, high alcohol consumption was negatively associated with T-Ad, HMW-Ad, and LMW-Ad levels only in those with ADH1B *2/*2. Such relationships were not observed in each ALDH2 genotype group. CONCLUSIONS: High alcohol consumption was inversely associated with T-Ad, HMW-Ad, and LMW-Ad levels in those with ADH1B *2/*2 genotype, but not in those with the other ADH1B genotypes. To our knowledge, this is the first study that reports combined effects of the alcohol-related polymorphisms and alcohol intake on serum adiponectin levels. Additional studies are required to confirm the present finding.

Habitual coffee consumption inversely associated with metabolic syndrome-related biomarkers involving adiponectin.

OBJECTIVES: The goal of this cross-sectional study was to assess whether habitual coffee consumption shows beneficial association with metabolic syndrome (MetS) in adults. METHODS: The association of coffee consumption and MetS-related biomarkers including visceral fat area (VFA) and subcutaneous fat area (SFA), total serum adiponectin (T-Ad), low-molecular-weight serum adiponectin (LMW-AD), medium-molecular-weight serum adiponectin (MMW-Ad), and high-molecular-weight serum adiponectin (HMW-Ad) levels were analyzed among 364 Japanese men (36-61 y old) using two models of multivariate regression analyses; model 1 (adjusted for age, alcohol drinking, smoking, and walking status) and model 2 (adjusted for body mass index in addition to model 1 analysis). Participants were categorized into two groups according to their MetS risk score (raised blood pressure and hemoglobin A1c levels, and reduced high-density lipoprotein cholesterol levels). RESULTS: Both light (1-3 cups/d) and moderate (≥4 cups/d) coffee consumption showed significant inverse associations with VFA and VFA/SFA ratio (P < 0.0001). Moderate coffee consumption showed a favorable tendency toward these associations with T-Ad (P = 0.06) and HMW-Ad (P = 0.07) levels in model 1 analysis. In participants with lower MetS risk score (≤1), moderate coffee consumption showed significant associations with T-Ad and HMW-Ad levels (P < 0.05) in both analyses, whereas no significant associations of coffee consumption with adiponectin levels were seen in the men with higher MetS risk scores (≥2). CONCLUSIONS: Habitual moderate coffee consumption shows significant inverse associations with MetS-related biomarkers possibly involving adiponectin, which is inversely related to visceral fat accumulation.

Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography.

With the aim of developing more efficient gastric cancer screening programs for use in Japan, we studied a new screening program that combines serum pepsinogen (PG) testing and barium digital radiography (DR). A total of 17 647 middle-aged male subjects underwent workplace screening over a 7-year period using a combination of PG testing and DR. This program's effectiveness, as well as other characteristics of the program, was analyzed. Forty-nine cases of gastric cancer were detected (comprising 88% early cancer cases). The detection rate was 0.28%, and the positive predictive value was 0.85%. The PG test detected 63.3% of cases, DR detected 69.4% of cases, and both tests were positive in 32.7% of cancer cases. The two methods were almost equally effective, and were considerably more effective than conventional screening using photofluorography. Each screening method detected a distinct gastric cancer subgroup; the PG test efficiently detected asymptomatic small early cancer with intestinal type histology, while DR was efficient at detecting cancers with depressed or ulcerated morphology and diffuse type histology. The cost for the detection of a single cancer was much less than that for conventional screening. In fact, it is possible to further reduce the cost of detecting a single cancer to a cost comparable to that of surgically resecting a single gastric cancer. Thus, it is probable that a highly efficient gastric cancer screening system can be implemented by combining the two screening methods. Such a screening program would be beneficial in a population at high risk for gastric cancer.

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer.

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.