Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China.

A case-control study was carried out to investigate the impact of factors including virus infection, aflatoxin B1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P4502E1 (CYP2E1), on susceptibility to hepatocellular carcinoma (HCC) in Haimen, China. A total of 248 patients with HCC and 248 sex-, age- and residence-matched population-based controls were recruited into the study. Virus infection, and ALDH2 and CYP2E1 gene polymorphisms were assessed in 134 paired cases and controls. By univariate analysis, hepatitis B virus (HBV) infection (odds ratio [OR]=9.75; 95% confidence interval [CI]=4.71-20.2), history of intravenous injection (OR=1.50; 95%CI=1.02-2.22), average income (OR=0.63; 95%CI=0.43-0.92), frequent intake of foods rich in protein, e.g., egg (OR=0.6; 95%CI=0.42-0.87), chicken (OR=0.53; 95%CI=0.35-0.79), pork (OR=0.67; 95%CI=0.46-0.98) and fresh fish (OR=0.58; 95%CI=0.39-0.87) significantly differed between cases and controls. However, peanut intake (OR=0.66; 95%CI=0.43-1.01), source of drinking water, including tap (OR=1.33; 95%CI=0.81-2.20), deep well (OR=0.94; 95%CI=0.56-1.55), shallow well (OR=0.85; 95%CI=0.55=1.30), river (OR=0.95; 95%CI=0.65-1.38), ditch (OR=1.09; 95%CI=0.76-1.55) and pond water (OR=1.0; 95%CI=0.14-7.10) were not significantly associated with risk. Univariate analysis also indicated that the 1-1 genotype of ALDH2 (OR=1.38; 95%CI=0.86-2.23) as well as the Pst1- and Rsa1-digested c1/c1 genotype of CYP2E1 (OR=1.36; 95%CI=0.81-2.28), was slightly more frequent in the case group. On multivariate analysis, HBV infection (OR=13.9; 95%CI=5.78-33.6) and history of intravenous injection (OR=2.72; 95%CI=1.24-6.00) were still associated with significantly increased risk of HCC, while frequent intake of fresh fish (OR=0.32; 95%CI=0.12-0.86) decreased this risk. These findings suggest that whereas peanut intake, water sources as well as genetic polymorphisms in ALDH2 and CYP2E1 do not significantly correlate with the risk of HCC, HBV infection is a main risk factor, and dietary items rich in protein, especially fresh fish, might protect against the risk of HCC in Haimen, China.     

Hepatitis B and C Viruses Infection, Lifestyle and Genetic Polymorphisms as Risk Factors for Hepatocellular Carcinoma in Haimen, China

A case‐control study was carried out to investigate the impact of factors including virus infection, aflatoxin B1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P4502E1 (CYP2E1), on susceptibility to hepatocellular carcinoma (HCC) in Haimen, China. A total of 248 patients with HCC and 248 sex‐, age‐ and residence‐matched population‐based controls were recruited into the study. Virus infection, and ALDH2 and CYP2E1 gene polymorphisms were assessed in 134 paired cases and controls. By univariate analysis, hepatitis B virus (HBV) infection (odds ratio [OR]=9.75; 95% confidence interval [CI] =4.71–20.2), history of intravenous injection (OR=1.50; 95%CI=1.02–2.22), average income (OR=0.63; 95% CI=0.43–0.92), frequent intake of foods rich in protein, e.g., egg (OR=0.6; 95% CI=0.42–0.87), chicken (OR=0.53; 95% CI=0.35–0.79), pork (OR=0.67; 95% CI=0.46–0.98) and fresh fish (OR=0.58; 95% CI=0.39–0.87) significantly differed between cases and controls. However, peanut intake (OR=0.66; 95% CI=0.43–1.01), source of drinking water, including tap (OR=1.33; 95% CI=0.81–2.20), deep well (OR=0.94; 95% CI=0.56–1.55), shallow well (OR=0.85; 95% CI=0.55‐–1.30), river (OR=0.95; 95% CI=0.65–1.38), ditch (OR=1.09; 95% CI=0.76–1.55) and pond water (OR=1.0; 95% CI=0.14–7.10) were not significantly associated with risk. Univariate analysis also indicated that the 1–1 genotype of ALDH2 (OR=1.38; 95% CI=0.86–2.23) as well as the Pst1‐ and Rsa1‐digested c1/c1 genotype of CYP2E1 (OR=1.36; 95% CI=0.81–2.28), was slightly more frequent in the case group. On multivariate analysis, HBV infection (OR=13.9; 95% CI=5.78–33.6) and history of intravenous injection (OR=2.72; 95% CI=1.24–6.00) were still associated with significantly increased risk of HCC, while frequent intake of fresh fish (OR=0.32; 95% CI=0.12–0.86) decreased this risk. These findings suggest that whereas peanut intake, water sources as well as genetic polymorphisms in ALDH2 and CYP2E1 do not significantly correlate with the risk of HCC, HBV infection is a main risk factor, and dietary items rich in protein, especially fresh fish, might protect against the risk of HCC in Haimen, China.     

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. ‍ ‍     

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.‍ ‍     

Genetic Polymorphism of Drug Metabolizing Enzymes (CYP2E1, GSTP1) and Susceptibility to Bladder Cancer in North India

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous ‍carcinogens and genetic polymorphisms of CYP2E1 and GSTP1 genes have been studied extensively to evaluate the ‍relative risk of various cancers. In the present study, we examined associations with CYP2E1 and GSTP1 gene ‍polymorphisms in sporadic bladder cancers from North Indian patients. The subjects were 106 bladder cancer (Ca- ‍B) cases and 162 age-matched controls. The GSTP1 313 A/G polymorphism was determined by the PCR/RFLP ‍method using peripheral blood DNA. Binary Logistic Regression Model was used for assessing differences in genotype ‍prevalence and their associations between patient and the control group. We observed a non-significant association ‍in Pst1 polymorphism of the CYP2E1 gene; though the A/G genotype (OR = 2.69, 95% CI=1.57- 4.59, P= 0.000) and ‍G/G genotype (OR = 7.68, 95% CI=2.77- 21.26, P= 0.000) of the GSTP1 gene polymorphism alone or in combination ‍with tobacco users were highly significant (OR=24.06; 95% CI: 4.80- 120.42; P =0.000) when compared to the ‍controls. The results of our study demonstrated that the GSTP1 313 G/G polymorphism is a strong predisposing ‍risk factor for bladder cancer in the North Indian population.     

Allele Frequencies of 25 Polymorphisms Pertaining to Cancer Risk for Japanese,Koreans, and Chinese

Allele frequencies are rather constant among different ethnic groups in many genetic polymorphisms, but some ‍polymorphisms vary in the allele frequency depending on the time when the germ-line base exchanges occurred in ‍the history of humans and on the adaptability of the phenotypes to given environment. This review documented the ‍allele frequencies of polymorphisms pertaining to cancer risk for Japanese, Koreans, and Chinese. Twenty-five ‍polymorphisms of 21 genes whose allele frequencies were available for at least two out of the three ethnic groups ‍were selected. They were ALDH2 Glu487Lys, COMT Val158Met, CYP1A1 MspI and Val/Ile, CYP1B1 Leu432Val, ‍CYP2E1 RsaI, CYP17 T-34C, ER C975G, GSTM1, GSTT1, GSTP1 Ile105Val, IL-1B C-511T, IL-1RN 86-bp VNTR ‍(variable number of tandem repeats), MTHFR C677T and A1298C, NAT1, NAT2, NQO1 Pro187Ser, OGG1 Ser326Cys, ‍p21 Ser31Arg, p53 Arg72Pro, TNF-A G-308A and G-238A, and XRCC1 Arg194Trp and Arg399Gln. The allele ‍frequencies were found for 24 in Japanese, 16 in Koreans, and 24 in Chinese. All of the polymorphisms had similar ‍allele frequencies for these ethnic groups, except the following polymorphisms; ALDH2 Glu487Lys whose Lys allele ‍was more common for Japanese and Taiwanese, COMT Val158Met whose Met allele was more common for Japanese, ‍and NAT2 rapid/slow whose slow alleles were more common for Chinese. When compared with the allele frequencies ‍among Caucasians, the following minor alleles were more frequent among Japanese/Koreans/Chinese; ALDH2 478Lys, ‍CYP1A1 m1 and m2, CYP2E1 c2, ER 975G, GSTT1 null, NAT1 *10, NQO1 187Ser, OGG1 326Cys, p21 31Arg, and ‍XRCC1 194Trp, and less frequent in COMT 158Met, GST-P1 105Val, IL-1RN non-4R, MTHFR 1298C, and TNF-A - ‍308A. The differences in genetic background may affect the impact on the lifestyle factors and/or genotypes examined ‍in epidemiological studies. However, the influences of the variations in the allele frequency seemed to be limited ‍among Japanese, Koreans, and Chinese. The substantial differences in the allele frequency from Caucasians could ‍modify the influences of lifestyle factors and polymorphism genotypes, resulting in the inconsistent results of ‍epidemiologic studies. ‍     

Independent and Additive Interaction Between Tumor Necrosis Factor β +252 Polymorphisms and Chronic Hepatitis B and C Virus Infection on Risk and Prognosis of Hepatocellular Carcinoma: a Case-Control Study

To assess the contribution of tumor necrosis factor (TNF)β +252 polymorphisms to risk and prognosis ofhepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patientswith cirrhosis alone, and unrelated healthy controls. TNFβ +252 genotypes were determined by polymerasechain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that TNFβ G/Ggenotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33),and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors forHCC. There was an additive interaction between TNFβ G/G genotype and chronic hepatitis B virus (HBV)/HCVinfection (synergy index=1.15). Multivariate analysis indicated that factors associated with TNFβ G/G genotypeincluded cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI,1.46-29.43), and higher serum α-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with TNFβG/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that TNFβ G/Ggenotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, thereare independent and additive effects between TNFβ G/G genotype and chronic HBV/HCV infection on risk forHCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity andadvanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCVinfected subjects with this genotype should receive more intensive surveillance for early detection of HCC.     

Insulin,Insulin-like Growth Factor-I and Breast Cancer Risk in Japanese Women

To evaluate the effects of glucose metabolism related factors, such as insulin and insulin-like growth-factors ‍(IGFs), on breast cancer development among Japanese women, we conducted a case-referent study comparing 187 ‍women presenting with operable breast cancer and 190 women of the same age having no breast cancer. Odds ratios ‍(OR) and 95% confidence intervals (95%CI) were determined by multiple logistic regression analysis. ‍ In the present study, no association in risk was observed with increasing levels of IGF-I or IGF binding protein- ‍3 (IGFBP-3), before or after adjustment these factors. However, a suggestion of a positive association of an increased ‍breast cancer risk was evident in postmenopausal women with elevated plasma insulin levels, particularly those with ‍BMI>23.07. The OR for plasma insulin in the top tertile was 4.48 (95%CI:1.07-18.7) compared to the bottom tertile. ‍For C-peptide, there was a similar positive association, with a corresponding OR of 2.28. In addition, we observed ‍strong links between plasma insulin, C-peptide levels and estrogen receptor (ER) negative breast cancer, with ORs ‍of 2.79(95%CI:1.09-7.16), and 2.52 (95%CI:0.91-6.97) respectively, for the top versus bottom tertiles. In conclusion, ‍the present study suggested that plasma insulin level is a predictor of postmenopausal breast cancer in obese women ‍and ER negative breast cancer. Additional studies are needed to clarify the role of glucose metabolism pathways in ‍breast cancer development and interaction of IGF systems.     

Association of CYP2E1 and NAT2 Polymorphisms with Lung Cancer Susceptibility among Mongolian and Han Populations in the Inner Mongolian Region

Purpose: To explore associations of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibilityamong Mongolian and Han populations in the Inner Mongolian region. Materials and Methods: CYP2E1 andNAT2 polymorphisms were detected by PCR-RFLP in 930 lung cancer patients and 1000 controls. Results: (1)Disequilibrium of the distribution of NAT2 polymorphism was found in lung cancer patients among Han andMongolian populations (p=0.031). (2) Lung cancer risk was higher in individuals with c1, D allele of CYP2E1RsaI/PstI, DraI polymorphisms and slow acetylation of NAT2 (c1 compared with c2, OR=1.382, 95%CI: 1.178-1.587, p=0.003; D compared with C, OR=1.241, 95%CI: 1.053-1.419, P<0.001; slow acetylation compared withrapid acetylation, OR=1.359, 95%CI:1.042-1.768, p=0.056) (3) Compared with c2/c2 and rapid acetylation, c1/c1together with slow acetylation synergetically increased risk of lung cancer 2.83 fold. (4) Smokers with CYP2E1c1/c1, DD, and NAT2 slow acetylation have 2.365, 1.916, 1.841 fold lung cancer risk than others with c2/c2, CCand NAT2 rapid acetylation, respectively. (5) Han smokers with NAT2 slow acetylation have 1.974 fold lungcancer risk than others with rapid acetylation. Conclusions: Disequilibrium distribution of NAT2 polymorphismwas found in lung cancer patients among Han and Mongolian populations. Besides, Han smokers with NAT2slow acetylation may have higher lung cancer risk compared with rapid acetylation couterparts. CYP2E1 c1/c1, DD and NAT2 slow acetylation, especially combined with smoking, contributes to the development of lungcancer. CYP2E1 c1/c1 or DD genotype and NAT2 slow acetylation have strong synergistic action in increasinglung cancer risk.     

Different Risk Relations with Smoking for Non-small-cell lung Cancer: Comparison of TP53 and TP73 Genotypes

Background: The association between TP53/TP73 gene polymorphisms and tobacco smoking was evaluated with ‍regard to risk of non-small cell lung cancer (NSCLC). Methods: A case-control study with 192 histologically confirmed ‍NSCLC cases and 241 non-cancer controls was conducted. Subjects were genotyped for TP53 Arg72Pro and TP73 ‍G4C14 to A4T14 polymorphisms by PCR-based methods. Risk and interactions were assessed as odds ratios (ORs) ‍and 95% confidence intervals (CIs). Results: The analyses according to TP53 genotypes for the risk of tobacco ‍smoking illustrated that risk with heavy smoking was much higher for subjects with the TP53 ProPro genotype ‍(OR: 16.4, 95% CI 1.77-151.7) as compared with those with TP53 ArgArg/ArgPro (3.36, 1.69-6.68). Similar analyses ‍for TP73 genotypes did not show any differences for NSCLC risk. Conclusion: A risk relation of heavy smoking for ‍the NSCLC is suggested with the TP53 but not the TP73 polymorphism. ‍     

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk of primary hepatocellular carcinoma in a chinese population.

Objective: To investigate the relationship of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genotypes as well as alcohol drinking to the susceptibility of primary hepatocellular carcinoma (HCC). Methods: A case-control study including 208 cases of HCC and 208 controls matched with sex, age and residential area was carried out in Taixing city of Jiangsu province, China. Blood samples were collected and tested for ADH2 and ALDH2 genotypes by PCR-RFLP method. Results: There were no significant differences in the frequency of either ADH2 or ALDH2 genotypes between cases and controls. Compared with no-drinkers possessing ALDH21*1 genotypes, drinkers with ALDH21*2 or ALDH22*2 genotypes and cumulative amount of alcohol consumption >3 (Kg * years) were at a significantly higher risk of developing HCC (OR=3.30, 95%CI: 1.24-8.83). In contrast, there was no significant difference in cancer risk between no-drinkers with ADH21*1 and drinkers with ADH2 1*2 or ADH22*2 genotypes. A dose-dependent positive result was found (P=0.044) between cumulative amount of alcohol consumption and the risk of HCC in individuals carrying ALDH21*2 or ALDH22*2 genotypes. Drinkers with cumulative amount of alcohol consumption >3 (Kg * years) who possessed both inactive ALDH2 (ALDH21*2 or ALDH22*2) and inactive ADH (ADH21*2 or ADH22*2) genotypes were not at a significantly higher risk of HCC (adjusted OR=4.26, 95%CI: 0.63-29.08) compared to no-drinkers possessing ADH21*1 and ALDH21*1 genotypes. Compared with individuals possessing ALDH21*1, with negative HBsAg and cumulative amount of alcohol consumption 3 (Kg * years) had a significantly higher risk of HCC (OR=49.71, 95%CI: 5.51-448.96). Conclusion: These results revealed that it was not ADH2 but ALDH2 polymorphisms that had a significant interaction with heavy alcohol consumption in the development of HCC. This result suggests that to help lower their risk for HCC , persons with ALDH21*2 or ALDH22*2 genotypes should be encouraged to reduce their consumption of alcoholic beverages.     

Multiphasic Epidemiological Analyses on Smoking Habits among Undergraduate Students in Japan

Little is known about the prevalence and dynamics of smoking habits among university students in Japan, and ‍their association with other lifestyle parameters and biological markers. Data on undergraduate students were here ‍extracted from the questionnaire and laboratory tests of the periodic health checkup of Kyoto University in 2000 ‍and 2001. In addition to simple statistics, longitudinal analyses were performed using logistic regression, and the ‍odds ratio (OR) and its 95% confidence interval (CI) were calculated for each item. Among 11,203 subjects, 12.1% ‍had a smoking habit. The smoking rate was higher in men than in women (14.4% vs 2.4%, P<0.001) and increased ‍from 2.5% (freshmen) to 18.3% (seniors) with advance in year. During one year of follow-up, 5.8% of students newly ‍acquired a smoking habit, and 12.4% of smokers abandoned the habit. Compared with students majoring in natural ‍sciences, the majors in humanities or social sciences were more likely to begin smoking (OR=1.32, 95% CI=1.06- ‍1.65). Taking up smoking was more common among those who consumed alcohol (OR=1.98, 95% Cl=1.56-2.51), and ‍skipped breakfast and dined out more frequently (trend P<0.001 for both), but less common among regular exercisers ‍(OR=0.71, 95% Cl=0.56-0.90). Smoking habits tended to be associated with subsequent proteinuria (adjusted OR=1.39, ‍95% Cl=0.96-2.00) and subsequent cough or phlegm (adjusted OR=1.56, 95% Cl=0.91-2.67). This study revealed ‍that the proportion of student smokers increases with the year in university, in association with several other lifestyle ‍parameters. Measures should be taken against smoking behavior focusing on freshmen and considering their lifestyle.     

Relationship between alcohol drinking, ADH2 and ALDH2 genotypes, and risk for hepatocellular carcinoma in Japanese

The polymorphism in the ALDH2 gene plays a central role in Asian alcohol hypersensitivity and has been associated with the risk for esophageal cancer. In the present study, we attempted to examine associations between the ADH2 and ALDH2 polymorphisms, alcohol drinking and hepatocellular carcinoma (HCC) development in a case-control study in Japan. One hundred and two patients with HCC (85 males and 17 females) and 125 control subjects (101 males and 24 females) were enrolled in the study. Higher cumulative amounts of alcohol consumption (drink-years of > or = 40 drinks/day x year) showed a significant association with HCC development (odds ratio, OR = 2.7; 95% CI = 1.3-5.5, adjusted for age and smoking). By contrast, we could find no association of the ALDH2 genotypes with HCC development (adjusted OR for ALDH2*1/*2 = 1.1; 95% CI = 0.6-2.1). Likewise, the ADH2 genotypes were not associated with HCC development (adjusted OR for ADH2*2/*2 = 0.8; 95% CI = 0.5-1.5). The present results do not support a contribution of acetaldehyde, an active metabolite of ethanol, to HCC development and rather indicate a direct involvement of ethanol in hepatocarcinogenesis.     

CYP2E1 PstI/RsaI polymorphism and interaction with alcohol consumption in hepatocellular carcinoma susceptibility: evidence from 1,661 cases and 2,317 controls

Many studies have suggested that cytochrome P450 2E1 (CYP2E1) gene might be involved in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between Pst I/Rsa polymorphism in the CYP2E1 gene and HCC risk. PubMed and China National Knowledge Infrastructure were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. Fifteen studies (1,661 HCC cases and 2,317 controls) were identified for the data analysis. The overall result showed that there was no statistically significant association between CYP2E1 Pst I/Rsa polymorphism and HCC risk (c2/c2 vs. c1/c1, OR = 0.73, 95% CI 0.50-1.06; c1/c2 vs. c1/c1, OR = 1.00, 95% CI 0.76-1.33; c2/c2+ c1/c2 vs. c1/c1, OR = 0.99, 95% CI 0.77-1.26; c2/c2 vs. c1/c2+ c1/c1, OR = 0.73, 95% CI 0.50-1.06). Further stratified analyses indicated that the habitual alcohol drinkers with c2 alleles were more likely to develop HCC (OR = 1.73, 95% CI 1.19-2.51), compared with the non-habitual drinkers with c1 homozygote. The meta-analysis indicated that CYP2E1 Pst I/Rsa polymorphism was not associated with HCC risk, while the interaction between Pst I/Rsa polymorphism and alcohol consumption increased the risk of HCC.     

N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study

Our aim was to evaluate the role of N-acetyltransferase (NAT2) and glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphisms in hepatocellular carcinoma (HCC) according to cigarette smoking, taking into account hepatitis B (HBV) and C (HCV) viral infection as well as alcohol consumption. A hospital-based case-control study was conducted in 2 areas of north Italy. Cases (n = 200) were patients hospitalized for HCC, and controls (n = 400) were patients admitted for reasons other than liver disease, neoplasms and tobacco- and alcohol-related diseases. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism-based method. The putative risk genotypes NAT2 slow acetylator, GSTM1 null and GSTT1 null were not associated with HCC (OR = 1.3, 95% CI 0.8-2.0; OR = 1.0, 95% CI 0.6-1.5; OR = 0.8, 95% CI 0.4-1.4, respectively). Although not statistically significant, an increase in HCC risk was observed among light smokers (1-20 pack-years) carrying GSTT1 null (OR = 1.7, 95% CI 0.6-4.7) and NAT2 slow acetylator (OR = 1.3, 95% CI 0.6-3.0) genotypes. In conclusion, there was no evidence for a gene-environment interaction in HCC risk for GSTM1, GSTT1 and NAT2 genotypes.     

Relationship between CYP1A1 genetic polymorphisms and renal cancer in China

Aim: To study the potential role of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms in the risk of renal cell cancer in Chinese. Methods: A total of 181 pathologically-proven renal cancers and 350 controls from the second Xiangya Hospital in Changsha were collected during the period from May 2007 to December 2010. CYP1A1 genetic polymorphisms were genotyped using PCR-RFLP. Unconditional logistic regression analysis was performed to analyze their relationship with risk of RCC. Results: Individuals with Val/Val genotypes had a significantly increased risk of RCC compared those with CYP1A1 IIe/IIe (OR=1.69, 95%CI=1.03-2.85). We also found CYP1A1 Wt/Vt and Vt/Vt to confer a significantly greater risk than CYP1A1 Wt/Wt (Wt/Vt: OR=2.14, 95%CI=1.24-3.45; Vt/Vt: OR=1.78, 95%CI=1.31-3.96). In smokers, a high increase risk of RCC was observed in those with CYP1A1 Val allele and Vt allele (Val allele: OR=2.13, 95%CI=1.40-2.57; Vt allele: OR=3.75, 95%CI=2.43-6.79), but no other significant interactions were found. Conclusion: Our study found suggestive evidence that CYP1A1 polymorphisms may play an important role in the etiology of RCC. Cigarette smoking may increase the susceptibility to RCC carcinogenesis in individuals with a high-risk genotype.     

Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming >or=3 "go"s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) = 13.5; 95% confidence interval (CI) 3.3-54.3] or CLD patients (adjusted OR = 7.0; 95% CI 2.5-19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 "go"s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR = 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR = 0.8 or 1.0; p interaction = 0.03 or 0.13). However, this gene-alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/*2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers.     

Variables Associated with Recurrence in Breast Cancer Patients -the Shaukat Khanum Memorial Experience

From a cohort of female breast cancer patients registered at the Shaukat Khanum Memorial Cancer Hospital ‍and Research Center, in Lahore, Pakistan, during the time period extending from December 1994 to December ‍2002, 700 subjects who were followed up in time, were selected. Those who presented with benign tumors, carcinoma ‍in situ, or metastases were excluded from the analyses. Age, tumor size, nodal status, menopause, estrogen receptor ‍(ER), and progesterone receptor (PR) status, at the time of presentation, were determined. Tumors were classified ‍according to the TNM classification (American Joint Commission on Cancer (AJCC)-sixth edition), and subsequently, ‍grouped into T1/T2 and T3/T4. Lymph nodes were categorized as N0 (node-negative) and N1, N2, and N3 combined ‍(node-positive). The odds ratio (OR) for developing recurrence in T3/T4 versus T1/T2 was determined to be 2.06 ‍(95% confidence interval (CI) 1.39-3.05, p < 0.001); the OR for node-positive relative to node-negative was found to ‍be 2.54 (95 % CI 1.61-4.0, p < 0.001). Furthermore, the association between the odds of developing recurrence in ‍ER-positive compared to ER-negative was represented by an OR of 0.61, (95 % CI 0.40-0.94 (p=0.02)). These findings ‍are consistent with the observations that ER-positive, node-negative, and T1/T2 lesions have a decreased risk of ‍recurrence. Also, ER-positive patients may have a better response to hormonal treatment than those who are ERnegative. ‍     

Methionine Synthase Reductase Gene A66G Polymorphism is Associated with Risk of Colorectal Cancer

A hospital-based case-control study was conducted to evaluate the significance of methionine and folate related ‍polymorphisms, with 72 colon and 70 rectal cancer cases and 241 non-cancer controls. The polymorphisms examined ‍were in the genes for methionine synthase reductase (MTRR A66G), methionine synthase (MTR A2756G) and ‍methylenetetrahydrofolate reductase (MTHFR C677T and A1298C). An unconditional logistic regression model ‍was applied for estimating the odds ratios (ORs) and 95% confidence intervals (CIs). The age-sex adjusted OR for ‍the MTRR GG genotype as compared with the AA and AG genotypes was 2.77 (95% CI: 1.39-5.53, p = 0.004), whereas ‍adjusted ORs for other polymorphisms were not statistically significant. When the ORs for environment factors ‍(smoking, alcohol consumption, body-mass-index, and physical exercise) were calculated according to each ‍polymorphism, no substantial difference was observed except with the MTRR polymorphism. The ORs for the MTRR ‍GG genotype seemed to be modified by the extent of environmental exposure. In conclusion, the present study ‍showed that the GG genotype of MTRR A66G is a risk factor for colorectal cancer in Japanese, while MTHFR and ‍MTR polymorphisms are not. The conclusions, however, need further evaluation in terms of micronutrient status ‍and additional confirmatory studies are required with datasets for various ethnic groups.