Relationship between Obesity and Serum Markers of Oxidative Stress and Inflammation in Japanese

The present study was conducted to assess the relationship between obesity and serum levels of C-reactive protein ‍(CRP), carotenoids, oxidized LDL (oxLDL), oxidized LDL antibodies (oLAB), and leptin in Japanese residents. ‍The subjects were 158 males and 158 females aged 40-79 years, and living in Hokkaido, Japan, who attended a ‍health examination screening. Serum levels of CRP, oxLDL, oLAB, and leptin were measured by enzyme-linked ‍immunosorbent assay (ELISA) and serum carotenoid levels were measured by high-performance liquid ‍chromatography (HPLC). Body mass index (BMI) was calculated as body weight (kg) divided by height (m) squared ‍and obesity was defined as BMI of 25 or more (kg/m2). ‍Serum levels of CRP and leptin were significantly higher in the obese group than in their non-obese counterparts ‍in both genders. Serum levels of â-carotene and â-cryptoxanthin were lower in the obese individuals, especially in ‍females. While values for oxLDL and oLAB did not significantly vary. BMI was positively correlated with logtransformed ‍serum levels of CRP and leptin in both genders (males: r=0.231, p<0.05; females: r=0.305, p<0.001). In ‍females, moreover, BMI was negatively correlated with log-transformed serum levels of â-carotene, zeaxanthin/ ‍lutein, and â-cryptoxanthin (r=-0.244, p<0.01; r=-0.200, p<0.05; r=-0.207, p<0.01, respectively). ‍Significantly higher odds ratios (ORs) for high serum levels of CRP (males: OR=2.12; females: OR=3.96) and ‍leptin (males: OR=3.83; females: OR=9.07) were observed in obese versus non-obese men and women, after adjusting ‍for various confounding factors. Significantly lower adjusted odds ratios for high serum levels of á- and â-carotenes ‍(males: OR=0.23, 0.33; females: OR=0.35, 0.39, respectively) were also observed in the obese as compared to the ‍non-obese group. ‍In conclusion, obesity is highly associated with states of oxidative stress and low-grade inflammation in Japanese ‍residents, suggesting that these latter might play an important role in the association between a high BMI and ‍certain cancers as well as coronary heart disease (CHD). ‍     

Cancer Mortality and Serum Levels of Carotenoids,Retinol, and Tocopherol: a Population-based Follow-up Study of Inhabitants of a Rural Area of Japan

A total of 3,182 subjects (1,239 males and 1,943 females) aged from 39y to 79y, were recruited from the inhabitants ‍of a rural area in Japan who participated in health check-up programs from 1988 to 1995. During the 10.5 year ‍follow-up, 287 deaths (175 males and 112 females) from all causes, 134 (81 males and 53 females) from cancer of all ‍sites, 31 from lung cancer, 21 from colorectal cancer, 20 from stomach cancer, and 62 from other cancers, were ‍identified among the cohort subjects. Fasting serum samples were taken at the time of the health check-ups, and ‍serum levels of carotenoids, retinol and tocopherols were separately determined by HPLC. Statistical analyses were ‍performed using Cox’s proportional hazard model after adjusting for sex, age, and other confounding factors. High ‍serum levels of á- and â- carotenes and lycopene were found to marginally significantly or significantly reduce the ‍risk for mortality rates of cancer of all sites and of colorectal cancers. High serum levels of â-cryptoxanthin also ‍showed an inversely relation with the risk of mortality from lung and stomach cancers, but this was not statistically ‍significant. High intake of green-yellow vegetables contributing to serum levels of á- and â- carotenes, as well as ‍lycopene, may reduce the risk of cancer mortality, especially from colorectal cancer, in rural Japanese.     

The Risk of Helicobacter Pylori Infection and Atrophic Gastritis from Food and Drink Intake: a Cross-sectional Study in Hokkaido

One-hundred and fifteen subjects were diagnosed with Helicobacter pylori (HP) infection and 93 subjects with ‍atrophic gastritis (AG) from tests of HP antibodies or serum levels of pepsinogen I and pepsinogen II involving 210 ‍inhabitants, who participated in the health check-up program. Logistic regression analysis found that refreshing ‍(isotonic) beverages significantly reduced the risk of HP infection (odds ratio: 0.767, 95%C.I.: 0.616-0.956). A higher ‍frequency of intake for margarine (odds ratio: 1.413, 95%C.I.: 1.080-1.848), cheese (odds ratio: 1.416, 95%C.I.: ‍1.044-1.920), Tsukemono (odds ratio: 1.277, 95%C.I.: 1.000-1.631) or Cola-beverages (odds ratio: 1.471, 95%C.I.: ‍1.051-1.239) showed a significantly increased risk of AG. In addition, high serum values of â-carotene (odds ratio: ‍0.691, 95%C.I.: 0.498-0.958), linoleic acid (odds ratio: 0.594, 95%C.I.: 0.382-0.924), and ã-linolenic acid (odds: 0.987, ‍95%C.I.: 0.976-0.998) were found to reduce the risk of AG, but not HP infection. Furthermore, these results suggest ‍that a more frequent intake of margarine, Tsukemono (pickled vegetables), or Cola-beverages may be a risk factor ‍for AG, while foods rich in carotenes, such as, â-carotene and n-6PUFAs, such as ã-linolenic acid, may reduce the ‍risk of AG.     

Serum g-glutamyl Transpeptidase and Alkaline Phosphatase of People in Khon Kaen,the Northeastern Thailand

Serum ã-glytamyl transpeptidase (GGT) and alkaline phosphatase (ALP) of the normal population in Northeastern ‍Thailand were measured. The median serum GGP and ALP levels of females was significantly lower than the values ‍for males, i.e., 21 (range=9-260) versus 32 (range=9-459) and 73 (range= 20-428) versus 83 (range=13-171) U/L, ‍respectively. Serum ALP level tended to increase with age in both male and female populations, whereas serum ‍GGT level did not show any age dependence. Serum GGT and ALP levels of cigarette smokers were significantly ‍higher than those of the non-smokers. Alcohol, coffee or tea drinking also resulted in higher serum GGT value ‍whereas serum ALP values were not changed. Betal nut chewing caused only lower serum GGT but not serum ALP ‍values. The total population in Ban Fang district seemed to have lower serum GGT than those in Chonnabot district. ‍The results from our study give the base line data of serum GGT and ALP in a Thai population. We also confirm the ‍association of serum GGT with cigarette smoking, alcohol and coffee/tea drinking which are risk factors of cancer. ‍     

Inhibitory Effects of Crude α-Mangostin,a Xanthone Derivative,on Two Different Categories of Colon Preneoplastic Lesions Induced by 1, 2-dimethylhydrazine in the Rat

The purpose of this study was to examine whether crude á-mangostin (a major xanthone derivative in mangosteen ‍pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved ‍in rat colon carcinogenesis. The crude preparation was obtained by simple recrystallization of an ethylacetate ‍extract of mangosteen pericarps. A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental ‍groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body ‍weight) once a week for 2 weeks. Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed ‍a diet containing 0.02% and 0.05% crude á-mangostin, respectively, for 5 weeks. Rats in group 4 also received the ‍diet containing 0.05% crude á-mangostin, while rats in group 5 served as untreated controls. The experiment was ‍terminated 5 weeks after the start. Dietary administration of crude á-mangostin at both doses significantly inhibited ‍the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude á-mangostin, P<0.01 for ‍0.05% crude á-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with ‍0.05% crude á-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and â-catenin accumulated crypts ‍(BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of ‍colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect ‍occurred in a dose dependent manner of the crude á-mangostin. This finding that crude á-mangostin has potent ‍chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might ‍result in suppression of tumor development. ‍     

Japanese Versus Mediteranean Diets and Cancer

Morbidity and mortality statistics, including incidences of fat-related cancers (FRCs), and dietary intake and ‍sources of fats and oils were compared for Japanese, Mediterranean and American people. Incidences of FRCs, ‍except for steeply increasing colon cancer, have remained low in Japan. Similarly, Mediterranean people enjoy ‍relatively low risks of FRCs compared with American people. The low risks of FRCs in Japanese may be explained ‍by limited intake of fats and oils as a whole, and a low ratio of n-6 polyunsaturated fatty acids (PUFAs) versus n- ‍3 PUFAs through consumption of the latter from marine foods. They also frequently consume vegetables and ‍fruit, and dietary fiber. Mediterranean people moderately consume fats and oils from a large amount of olive ‍oil, containing not only oleic acid but also polyphenols (including flavonoids), á-tocopherol and carotenoids ‍(including â-carotene), which are antioxidants and anti-carcinogenic as in red wine, vegetables (including herbs) ‍and fruit. The diet also features medium intake of fish and shellfish along with cereals/pasta/bread. From the ‍standpoint of intake of total fat, the low risks of FRCs in Japanese seem "plausible," while the low risks in ‍Mediterranean people may be termed "paradoxical." In summary, limited consumption of fats and oils, moderate ‍intakes of marine foods, and vegetables and fruit, in line with a modest intake of energy may be advocated for ‍promoting health, prolonging life and prevention of lifestyle-related diseases including FRCs.     

Risk Factors for Esophageal Cancer: a Case-control Study in South-western China

Esophageal cancer is a crucial cancer in China. Yanting in Sichuan Province was a key area with highest esophageal ‍cancer mortality in China, but little evidence on esophageal cancer risk factors has been reported for this area and ‍the etiology remains unclear. To clarify risk factors, a 1:1 matched case-control study was conducted. Totals of 185 ‍eligible esophageal cancer patients and 185 healthy residents matched for sex and age were recruited. Conditional ‍logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for possible risk/ ‍protective factors. All ORs were adjusted by family history of esophageal cancer and occupation, and then further ‍adjusted by other possible confounding factors. Our results showed that smoking and alcohol drinking were risk ‍factors for esophageal cancer with dose-response. The ORs (95% CI) compared with never smokers and drinkers ‍were 4.06 (1.55-10.6) and 2.49 (1.06-5.85), respectively. The OR was further increased to 8.86 (95%CI, 3.82-20.5) for ‍both smoking and drinking in combination. Eating food rapidly (OR=5.84, 95%CI, 2.05-16.7), drinking shallow ‍ground water (OR=4.18, 95%CI, 1.30-13.4) and frequent intake of picked vegetables (OR=2.12, 95%CI, 1.00-4.49) ‍appeared to increase the risk, while frequent intake of fresh fruit (OR=0.42, 95%CI, 0.19-0.89), fresh vegetables ‍(OR= 0.62, 95%CI, 0.32-1.17) and eggs (OR=0.59, 95%CI, 0.25-1.39) decreased the risk. In conclusion, smoking and ‍alcohol drinking are common in Yanting and main contributors to esophageal cancer. Consumption of fresh fruit ‍and eggs are not common and high consumption of these two foods as well as fresh vegetables may decrease the risk ‍of esophageal cancer in this area. In addition, drinking shallow ground water and eating food rapidly, as well as ‍frequent intake of pickled vegetables, are also factors increasing the risk. ‍ ‍     

A Population-based Case-control Study of Risk Factors and Genetic Polymorphisms of ALDH2 and P4502E1 for Hepatocellular Carcinoma in Nagoya,Japan

A population-based case-control study was carried out to investigate risk factors for hepatocellular carcinoma ‍(HCC) in Nagoya, Japan, including hepatitis virus infections, drinking and smoking habits and genetic polymorphisms ‍in aldehyde dehydrogenase2 (ALDH2) and cytochrome P4502E1 (CYP2E1). A total of 84 patients with HCC and 84 ‍sex, age and residence pair-matched controls were recruited for this study. By univariate analysis, hepatitis B virus ‍(HBV) (OR=5.14; 95%CI=2.29-11.6) and hepatitis C virus (HCV)(OR=32.00; 95%CI=7.83-130.7) infections, having ‍a history of blood transfusion (OR=5.25; 95%CI=1.80-15.29), and habitual smoking (OR=2.36; 95%CI=1.17-4.78) ‍were significantly linked to cases; by multivariate analysis, HCV infection (OR=23.5; 95%CI=5.07-108.9) and habitual ‍smoking (OR=5.41; 95%CI=1.10-26.70) were still associated with a significantly increased risk. The c1/c1 genotype ‍of CYP2E1 (odds ratio [OR]= 0.45; 95% confidence interval [CI]=0.21-0.99), detected by Pstl and Rsal digestion was ‍significantly more prevalent in the control group, while 1-1 genotype of ALDH2 (OR=1.24; 95%CI=0.70-2.20) did ‍not demonstrate variation. There were no statistically significant interactions between habitual smoking/drinking ‍and genetic polymorphisms of ALDH2/P4502E1 with reference to HCC development. These findings suggest that ‍viruses, especially HCV infection, and habitual smoking are major independent risk factors, while genetic ‍polymorphisms of ALDH2 and CYP2E1 have only limited contribution to the risk of HCC in Nagoya, Japan.     

Gastric Cancer: the Roles of Diet,Alcohol Drinking,Smoking and Helicobacter pylori in Northeastern Thailand

The incidence of gastric cancer in the countries of South East Asia is variable, ranging from age-standardized ‍rates of 20.9/105 (men) and 10.4/105 (women) in Hanoi, Vietnam to 4.1/105 (men) and 2.1/105 (women) in Khon Kaen, ‍Thailand. The reasons for these differences are unknown. Possible explanations are differences in dietary habits, ‍alcohol drinking, smoking and/or the prevalence of infection with Helicobacter pylori (H. pylori). A case-control ‍study was conducted in Khon Kaen, Thailand, to study the role of these factors in gastric cancer carcinogenesis. 131 ‍gastric cancer cases and 262 matched controls were recruited for the study. Information on dietary habits, alcohol ‍drinking and smoking were collected by a structured questionnaire. Blood samples were available from 111 cases ‍and 232 controls for H. pylori assay. Using an unconditional logistic regression model controlling for age and sex, we ‍assessed the effects of dietary habits, alcohol drinking, smoking and H. pylori infection on the risk of gastric cancer. ‍A high intake of salt (OR=1.8; 95%CI 1.1-3.0) and fermented foods (OR=1.9; 95%CI 1.1-3.3) was found to be ‍associated with an increased risk. Preference for spicy food was not associated with gastric cancer risk in this ‍population. Although there were negative associations between gastric cancer and vegetable and fruit intake, they ‍were rather weak (OR 0.8 for both) and non significant. There were also weak (non-significant) associations with ‍smoking and alcohol consumption, and no association with H. pylori infection (OR=0.6; 95%CI 0.4-1.0). Infection of ‍H. pylori was associated with various indicators of crowding. ‍     

Serum Carotenoid,Retinol and Tocopherol Concentrations and Risk of Cervical Cancer among Chinese Women

Background: Despite many epidemiological studies on the effects of dietary antioxidant micronutrients on riskof cervical cancer, the findings remain uncertain and little evidence is available for serum nutrient markers. Thepresent study aimed to examine the relationship between serum carotenoid, retinol and tocopherol concentrationsand risk of cervical cancer among Chinese women. Materials and Methods: We conducted a hospital-based casecontrolstudy in which 358 adults (158 incident cases and 200 controls) were recruited from Xinjiang, China.Serum levels of carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin), retinol,and tocopherols (α-tocopherol and γ-tocopherol) were assessed by reverse-phase high-performance liquidchromatography. Results: We found inverse associations between serum carotenoid (α-carotene, β-carotene, andlutein/zeaxanthin) and tocopherol (α-tocopherol) concentrations and the risk of cervical cancer after adjustingfor potential confounders, but a null association for retinol. The ORs for 1-SD increase were 0.71 (95 % CI: 0.56-0.92; p=0.003) for total carotenoids and 0.75 (95 % CI: 0.60-0.94; p=0.008) for total tocopherols. Conclusions:These results show that higher serum concentrations of some carotenoids and tocopherols are associated witha lower risk of cervical cancer among Chinese women.     

Dietary Habits and Cancer Mortality Among Middle Aged and Older Japanese Living in Hokkaido,Japan by Cancer Site and Sex

Dietary factors are thought to be closely associated with the development of human cancers and hence numerous studies ‍in this area have already been conducted in the United States and other Western countries. Comparatively few prospective ‍studies have been published in Japan, especially for Hokkaido people. The present investigation was therefore performed to ‍assess links between four leading cancers and some of the Japanese common dietary factors through a cohort study (1984- ‍2002) in Hokkaido by analyzing 1,524 men and 1,634 women separately aged 40 and over. Adjusted Cox proportional ‍hazard regression was used to calculate the relative risk (RR) for each dietary factor. For men, two dietary factors, miso ‍soup (RR=0.2, 95% confidence interval (95%CI)=0.1-0.8) and pickled vegetables (RR=0.2, 95%CI=0.1-0.8) were associated ‍with lower risk for stomach and colorectal cancer respectively. For women, three factors, namely salty confectionary (RR=3.5, ‍95%CI=1.1-10.9), black tea (RR=3.8, 95%CI=1.1-13.6), and carbonated drink/juice (RR=3.9, 95% CI=1.4-11.1) appeared ‍related to an elevated risk of stomach cancer. However, further analysis simultaneously with all other adjusted factors ‍indicated only carbonated drink/juice (RR=3.1, 95%CI=1.1-8.9) to present a significant risk factor for stomach cancer. One ‍factor, namely wild edible plants (RR=3.3, 95%CI=1.1-9.8), increased the risk for colorectal cancer in women. None of the ‍dietary components were significantly associated with lung or pancreatic cancers. This study also indicated a wide variation ‍in the impact of dietary factors by sex and cancer site, in line with earlier work, poonting to a necessity for careful interpretation. ‍Further epidemiological investigations by sex with more study subjects and confounding factors will be useful for determining ‍the contribution of individual dietary factors to development of human cancers in Hokkaido, Japan.     

High Serum Level of Retinol and α-Tocopherol Affords Protection Against Oral Cancer in a Multiethnic Population

Background: A comparative cross-sectional study involving oral cancer patients and healthy individuals wasdesigned to investigate associations between retinol, α-tocopherol and β-carotene with the risk of oral cancer.Materials and Methods: This study included a total of 240 matched cases and controls where subjects wereselected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopheroland β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and foodfrequency questionnaire (FFQ) respectively. Results: It was found that results from the two methods applied didnot correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels ofretinol and α-tocopherol among cases (0.177±0.081, 1.649±1.670μg/ml) were significantly lower than in controls(0.264±0.137, 3.225±2.054μg/ml) (p<0.005). Although serum level of β-carotene among cases (0.106±0.159 μg/ml)were lower compared to controls (0.134±0.131μg/ml), statistical significance was not observed. Logistic regressionanalysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and α-tocopherol(OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas norelationship was observed between β-carotene and oral cancer risk. Conclusions: High serum levels of retinoland α-tocopherol confer protection against oral cancer risk.     

Chemopreventive Action of Emblica Officinalis on Skin Carcinogenesis in Mice

Chemoprevention with food phytochemicals is currently regarded as one of the most important strategies for ‍cancer control. Emblica officinalis (Family: Euphorbiaceae) indigenous to India, is valued for its unique tannins and ‍flavanoids, which contain very powerful antioxidant properties. The inhibition of tumor incidences by fruit extract ‍of this plant has been evaluated on two-stage process of skin carcinogenesis in Swiss albino mice, induced by a single ‍application of 7, 12-dimethyabenz(a)anthrecene (100 ìg/ 100 ìl acetone), and two weeks later, promoted by repeated ‍application of croton oil (1% in acetone/thrice a week) till the end of the experiment (16 weeks). The tumor incidence, ‍tumor yield, tumor burdon and cumulative number of papillomas were found to be higher in the control (without ‍EO treatment) as compared to experimental animals (EO treated). The differences in the values of the results of ‍experimental groups were statistically analysed and found to be significant in comparison to the control group (p< ‍0.05). The present study demonstrates the chemopreventive potential of Emblica officinalis fruit extract on DMBA ‍induced skin tumorigenesis in Swiss albino mice. ‍     

The p53 Codon 72 Polymorphism and Risk of Oral Cancer in Southern Thailand

The codon 72 polymorphism of the p53 tumor suppressor gene has been investigated extensively for its association ‍with various cancers around the world. However, its influence has not been elucidated in the Thai population. ‍Therefore, a case-control study with 97 patients and 97 matched controls was conducted to elucidate the association ‍between the polymorphic p53 and oral cancer risk in a Southern Thai population. The frequencies of the Arg/Arg, ‍Arg/Pro, and Pro/Pro genotypes were 36%, 35%, and 29%, respectively in the controls and 33%, 45% and 22%, ‍respectively in the patients. This study shows that there was no significant association between the p53 codon 72 ‍polymorphism and oral cancer risk. There was also no link with respect to smoking or drinking habits. However, ‍our data suggest that for individuals who were younger than 65 years old, the Pro/Pro genotype may offer some ‍protection against oral cancer (OR = 0.13, 95%CI 0.04-1.10). This is the first report on p53 polymorphism and oral ‍cancer in Thailand.‍ ‍     

A Case-control Study of Multiple Myeloma in Japan: Association with Occupational Factors

Recently the incidence rate of multiple myeloma (MM) has increased in Japan. Epidemiologic efforts have suggested ‍that certain occupational and chemical exposures are likely to increase the risk for MM. We therefore performed a ‍case-control study of MM, examining occupational factors. Data for 57 cases and 57 controls were obtained from ‍Sapporo Medical University Hospital and its affiliated hospitals in Hokkaido. Controls were matched to each case ‍by gender, age (+ 5 years) and hospital. Detailed information regarding several factors possibly related to MM was ‍obtained by interviews in hospitals. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated with ‍adjustment for cigarette smoking as confounding factor. The occupational category of agriculture and fishery showed ‍a significant association with increased risk (OR = 5.89, 95%CI = 1.24-28.04). Occupational exposure to chemical ‍products including organic solvents or petroleum showed a significant association with increased risk (OR = 8.05, ‍95%CI = 1.01-64.45). Medical histories of operation for appendicitis and blood transfusion were associated with ‍decreased risk, but not significantly. Our results suggested that occupational exposure to chemicals might play a role ‍in the risk of MM. ‍ ‍     

GSTT1 and GSTM1 Deletions,NQO1 C609T Polymorphism and Risk of Chronic Myelogenous Leukemia in Japanese

We conducted a prevalent case-control study with 51 chronic myelogenous leukemia (CML) cases and 476 controls ‍to investigate the associations between glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1 (GSTM1) ‍deletions, and the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism with risk of chronic myelocytic ‍leukemia in Japanese. For the GSTT1 deletion, when the GSTT1 positive genotype was defined as the reference, the ‍OR for the GSTT1 deletion genotype was 1.32 (95%CI; 0.74-2.36). For the GSTM1 deletion, when the GSTM1 ‍positive genotype was defined as the reference, the OR for the GSTM1 deletion genotype was 0.95 (95%CI; 0.53- ‍1.69). For NQO1 C609T polymorphism, when the NQO1 609CC genotype was defined as the reference, the ORs for ‍the CT genotype, TT genotype, and CT and TT genotypes combined together were 2.37 (95%CI, 1.21-4.67, P=0.012), ‍1.44 (0.55-3.74, P=0.012) and 2.12 (1.10-4.08, P=0.025), respectively. The present study revealed that the risk of CML ‍was modulated little by GSTT1 and GSTM1 deletions, but a statistically significant association between NQO1 C609T ‍polymorphism and CML was observed for Japanese. Incidence case-control studies with a larger statistical power ‍are now required to confirm our findings.     

Relation of the CD36 Gene A52C Polymorphism to the Risk of Colorectal Cancer Among Japanese,with Reference to with the Aldehyde Dehydrogenase 2 Gene Glu487Lys Polymorphism and Drinking Habit

High consumption of white meat (or saturated fatty acids) and alcohol has been demonstrated to have a tendency ‍to increase the risk of colorectal cancer, according to the level of malondialdehyde-deoxyguanosine adducts derived ‍from lipid per-oxidation in the colorectal mucosa. CD36 plays important roles as a long-chain fatty acid translocase ‍and oxidized low-density lipoprotein (LDL) scavenger, while alcohol is metabolized by aldehyde dehydrogenase 2 ‍(ALDH2) and decreases transiently metabolism of dietary fat and serum lipids. To examine associations between the ‍risk of colorectal cancer and the CD36 gene A52C polymorphism according to the ALDH2 gene Glu487Lys ‍polymorphism and drinking habit, a hospital-based case-control study was conducted with 128 colorectal cancer ‍cases and 238 cancer-free controls. Odds ratios (ORs) for the C/C genotype relative to the A/A genotype were 1.70 ‍[95% confidence interval (CI), 0.76-4.11] and 4.24 (95% CI, 1.42-22.66) for men and women, respectively, with the ‍low-activity (Glu/Lys + Lys/Lys) ALDH2 genotype. The high-activity (Glu/Glu) genotype for men and women had no ‍associations. On the other hand, the OR for the C/C genotype with high frequency of drinking habit relative to the ‍A/A genotype with low frequency of drinking habit among men was 3.63 (95% CI, 1.29-13.15). The number of ‍women with a high frequency drinking habit was too small for any corresponding analyses. Our findings suggest a ‍significant interaction between alcohol consumption and the CD36 gene A52C polymorphism related to the metabolism ‍of long-chain fatty acids and oxidized LDL in the etiology of colorectal cancer.     

Effects of Three-month Oral Supplementation of β-Carotene and Vitamin C on Serum Concentrations of Carotenoids and Vitamins in Middle-aged Subjects: A Pilot Study for a Randomized Controlled Trial to Prevent Gastric Cancer in High-risk Japanese Population

Prior to a randomized controlled trial to prevent gastric cancer by oral supplementation of β-carotene and vitamin C in a high-risk Japanese population, we examined the serum response to threemonth oral supplementation of β-carotene (0, 3, 30 mg/day) and vitamin C (0, 50, 1000 mg/day) by a three-by-three factorial design using 54 subjects (age range=40–69 years). Serum concentrations of carotenoids, α-tocopherol, and ascorbic acid were examined at baseline, and one, two, and threemonth points. Both serum β-carotene and ascorbic acid were significantly higher in high-dose groups than in each placebo group during the supplementation. The serum β-carotene increased gradually (597–830% increase) during the study, whereas the serum ascorbic acid reached nearly a steady-state at the one-month point and remained stable thereafter (88–95% increase). No statistically significant interaction between β-carotene and vitamin C supplementations was observed either for serum β-carotene or for serum ascorbic acid. Among carotenoids and α-tocopherol examined, serum lycopene in the high-dose β-carotene group was significantly higher than in the placebo group at all points. No unfavorable change in carotenoids and α-tocopherol was observed in any group.     

Esophageal Cancer Risk by ALDH2 and ADH2 polymorphisms and Alcohol Consumption: Exploration of Gene-Environment and Gene-Gene Interactions

Alcohol drinking is a major risk factor for esophageal cancer in Japan and its impact may be modulated by levels ‍of ALDH2, ADH2 and CYP2E1, three representative alcohol-metabolizing enzymes which display genetic ‍polymorphisms altering individual alcohol-oxidizing capacity and drinking behavior. To assess the actual influence ‍of ADH2 Arg47His, ALDH2 Glu487Lys and CYP2E1 variant c2 allele polymorphisms on esophageal cancer risk ‍with conjunction with alcoholic consumption, the present 1:3 matched case-control study was conducted. The 165 ‍histologically diagnosed Japanese esophageal cancer cases were here compared with 495 randomly selected controls, ‍matched with respect to sex and age. Conditional logistic regression was used to calculated Odds Ratios (ORs) and ‍95% confidence intervals (95% CI). Significant gene-environment interactions between alcohol drinking and both ‍ADH2 and ALDH2 were observed regarding esophageal cancer risk. The ADH2 Arg47His polymorphism showed ‍moderately increased risk (OR for Arg/His and Arg/Arg relative to His/His: 2.01 (1.39-2.90)). In the ALDH2 case, ‍comparing the Glu/Lys with the Glu/Glu genotype, ORs were markedly increased to 9.64 (3.23-28.8) and 95.4 (28.7- ‍317) from 1.88 (0.42-8.37) and 4.62 (0.93-23.1) for moderate drinking and heavy drinking, respectively. No significant ‍alteration in risk was observed with the CYP2E1 polymorphism. In conclusion, the present study revealed a significant ‍gene-environment interaction between alcohol drinking and the ALDH2 polymorphism regarding esophageal cancer ‍risk among a general population in Japan, providing concrete evidence of a role for acetaldehyde in neoplastic ‍development. Interactions between ALDH2 and ADH2 need further clarification.‍ ‍     

Suppressive Effects of Okinawan Food Items on Free Radical Generation from Stimulated Leukocytes and Identification of Some Active Constituents: Implications for the Prevention of Inflammation-associated Carcinogenesis

Okinawa prefecture in Japan is a distinct area characterized by unique traditional food habits and longevity. ‍Prolonged exposure to activated leukocytes, playing pivotal roles in chronic inflammation-associated carcinogenesis, ‍is known to lead to oxidative and nitrosative damage to macromolecules in the body since they are primary sources ‍of free radicals, such as superoxide anion (O2 ‍-) and nitric oxide (NO). In this study, we estimated anti-oxidative and ‍anti-nitrosative activities of Okinawan food items by employing two cellular experimental systems: (1) phorbol ‍ester-induced O2 ‍- generation from differentiated HL-60 human promyelocytic leukemia cells; and (2) ‍lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages. A total of 138 food items, ‍consisting of 42 samples unique to Okinawa and 96 common in the Japanese main island, were purchased at local ‍markets in Okinawa and extracted with chloroform. When tested at a concentration of 100 ìg/ml, 38% (16/42) of ‍the former showed 70% or more inhibition of O2 ‍- generation while 21% (20/96) of the latter did so. In parallel, 64% ‍(27/42) of the former showed significant NO generation suppression in contrast to 48% (46/96) of the latter . Twentyone ‍active species were further tested at a concentration of 20 ìg/ml, and eleven species, including sugar cane, wild ‍turmeric, and zedoary, were indicated to be most promising items with anti-oxidative and anti-nitrosative properties. ‍In addition, some of the active constituents (chebulagic acid, a resveratrol derivative, and sesquiterpenoids) were ‍identified. Our results suggest that food items typical in the Okinawa area have higher cancer preventive potential ‍than those common in Japan.