Article

A novel polymorphism rs1329149 of CYP2E1 and a known polymorphism rs671 of ALDH2 of alcohol metabolizing enzymes are associated with colorectal cancer in a southwestern Chinese population.

Department of Hygienic Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
Cancer Epidemiology Biomarkers &amp Prevention (Impact Factor: 4.56). 09/2009; 18(9):2522-7. DOI:10.1158/1055-9965.EPI-09-0398
Source: PubMed

ABSTRACT To screen for tagging single nucleotide polymorphisms (tagSNP) in the major alcohol metabolizing enzymes: ADH1B, ALDH2, and CYP2E1, and to evaluate the association between these tagSNPs and colorectal cancer (CRC) in a southwestern Chinese population.
A hospital-based case-control study of 440 CRC patients and 800 cancer-free controls was conducted. Personal information was collected by a Semi-Quantitative Food Frequency Questionnaire. The tagSNPs were screened in the HapMap with Haploview by setting the minor allele frequency at 0.03 with the highest score of r(2) form each block. Genotypes were identified by using the SNPLex System. Both crude and adjusted odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risk of each SNP.
Sixteen tagSNPs were selected, and 13 were successfully genotyped. A novel CYP2E1 locus rs1329149 and a known ALDH2 locus rs671 were found to be significantly associated with CRC risk. The adjusted OR was 1.86 (95% CI, 1.12-3.09) for the rs671 A/A genotype and 4.04 for the rs1329149 T/T genotype (95% CI, 2.44-6.70), compared with their common homozygous genotypes. Interaction was found between alcohol consumption and gene polymorphisms on CRC, the adjusted OR was 7.17 (95% CI, 2.01-25.53) for drinking habits combined with rs671 A/A or rs1329149 T/T genotype.
The results of this study suggest that rs671 A/A and the first reported locus rs1329149 T/T genotypes increase the susceptibility to CRC, and gene-environmental interaction between the two loci and alcohol use existed for CRC in Southwestern Chinese. Larger studies are warranted to verify our findings.

0 0
 · 
0 Bookmarks
 · 
70 Views
  • [show abstract] [hide abstract]
    ABSTRACT: We aimed at investigating the risk of bladder cancer at different levels of alcohol consumption by conducting a meta-analysis of epidemiological studies. In October 2010, we carried out a systematic literature search in the Medline database, using PubMed. We identified 16 case-control and 3 cohort studies, including a total of 11 219 cases of bladder cancer, satisfying the inclusion criteria for this meta-analysis. Moderate alcohol intake was defined as <3 drinks per day (i.e. <37.5 g of ethanol per day) and heavy intake as ≥3 drinks/day. Pooled estimates of the relative risks (RR) and the corresponding 95% confidence intervals (CI) were calculated using random effects models. Compared with non-drinkers, the pooled RRs of bladder cancer were 1.00 (95% CI 0.92-1.09) for moderate and 1.02 (95% CI 0.78-1.33) for heavy alcohol drinkers. When we excluded four studies that did not adjust for tobacco smoking, the corresponding estimates were 0.98 (95% CI 0.89-1.07) and 0.97 (95% CI 0.72-1.31). This meta-analysis of epidemiological studies provides definite evidence on the absence of any material association between alcohol drinking and bladder cancer risk, even at high levels of consumption.
    Annals of Oncology 10/2011; 23(6):1586-93. · 7.38 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: A large number of common disorders, including cancer, have complex genetic traits, with multiple genetic and environmental components contributing to susceptibility. A literature search revealed that even among several meta-analyses, there were ambiguous results and conclusions. In the current study, we conducted a thorough meta-analysis gathering the published meta-analysis studies previously reported to correlate any random effect or predictive value of genome variations in certain genes for various types of cancer. The overall analysis was initially aimed to result in associations (1) among genes which when mutated lead to different types of cancer (e.g. common metabolic pathways) and (2) between groups of genes and types of cancer. We have meta-analysed 150 meta-analysis articles which included 4,474 studies, 2,452,510 cases and 3,091,626 controls (5,544,136 individuals in total) including various racial groups and other population groups (native Americans, Latinos, Aborigines, etc.). Our results were not only consistent with previously published literature but also depicted novel correlations of genes with new cancer types. Our analysis revealed a total of 17 gene-disease pairs that are affected and generated gene/disease clusters, many of which proved to be independent of the criteria used, which suggests that these clusters are biologically meaningful.
    Human genomics 06/2013; 7(1):14.
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants.
    PLoS ONE 01/2013; 8(11):e80158. · 3.73 Impact Factor

Full-text

View
3 Downloads
Available from
Mar 28, 2014