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 & Prevention (Impact Factor: 4.32). 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.

Download full-text


Available from: Huan Yang, Mar 28, 2014
  • Source
    • "Selected Asian populations have higher frequencies of ADH1B*2 and ALDH2*2 mutant alleles (up to 40%) than Caucasians (<5%) [34]. ADH1B and ALDH2 polymorphisms have been related to the risk of selected cancers, particularly of the upper aerodigestive tract, in alcohol drinkers [35] [36] [37] of Asian descendents, while studies conducted in European populations found no significant association with ADH1B*1, whereas practically all Europeans were homozygous for ALDH2*1 [38]. However, since we identified only four studies from Asia [6] [13] [16] [17], this finding needs further confirmation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The association between alcohol and leukemia risk has been addressed in several studies in the past two decades, but results have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to quantify the dose–risk relation. Through the literature search up to August 2013, we identified 18 studies, 10 case-control and 8 cohorts, carried out in a total of 7142 leukemia cases. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we performed a dose–risk analysis using a class of nonlinear random-effects meta-regression models. Stratified analyses were carried out on leukemia subtypes and groups, in order to identify possible etiologic differences. Compared with nondrinkers, the relative risks (RRs) for all leukemia were 0.94 [95% confidence interval (CI), 0.85–1.03], 0.90 (95% CI, 0.80–1.01) and 0.91 (95% CI, 0.81–1.02) for any, light (≤1 drink/day) and moderate to heavy (>1 drink/day) alcohol drinking, respectively. The summary RRs for any alcohol drinking were 1.47 (95% CI, 0.47–4.62) for acute lymphoblastic leukemia, 0.94 (95% CI 0.77–1.15) for chronic lymphocytic leukemia, 1.02 (95% CI, 0.86–1.21) for acute myeloid leukemia and 0.93 (95% CI 0.75–1.14) for chronic myeloid leukemia. The subgroup analysis on geographical area for all leukemia combined showed RRs of 0.84 (95% CI, 0.76–0.93), 0.92 (95% CI, 0.83–1.01) and 1.32 (95% CI, 1.02–1.70) for studies conducted in America, Europe and Asia, respectively. We did not find an increased risk of leukemia among alcohol drinkers. If any, a modest favorable effect emerged for light alcohol drinking, with a model-based risk reduction of approximately 10% in regular drinkers.
    Cancer Epidemiology 06/2014; 38(4):339-345. DOI:10.1016/j.canep.2014.06.001 · 2.56 Impact Factor
  • Source
    • "At the level of , Forward LR analysis was applied to select variables, and the results are shown in Table 2. Gene rs671, rs1329149, age, and alcohol consumption correlate with the morbidity of colorectal cancer. Based on OR, all of these four factors are risk factors for the pathogenesis of colorectal cancer, which is consistent with results in the literature (Yang et al., 2009). Next, the interactions between these factors were analyzed by combining crossover analysis and logistic regression methods. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Analysis of gene-gene and gene-environment interactions for complex multifactorial human disease faces challenges regarding statistical methodology. One major difficulty is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes or environmental exposures. Based on our previous case-control study in Chongqing of China, we have found increased risk of colorectal cancer exists in individuals carrying a novel homozygous TT at locus rs1329149 and known homozygous AA at locus rs671. In this study, we proposed statistical method- crossover analysis in combination with logistic regression model, to further analyze our data and focus on assessing gene-environmental interactions for colorectal cancer. The results of the crossover analysis showed that there are possible multiplicative interactions between loci rs671 and rs1329149 with alcohol consumption. Multi- factorial logistic regression analysis also validated that loci rs671 and rs1329149 both exhibited a multiplicative interaction with alcohol consumption. Moreover, we also found additive interactions between any pair of two factors (among the four risk factors: gene loci rs671, rs1329149, age and alcohol consumption) through the crossover analysis, which was not evident on logistic regression. In conclusion, the method based on crossover analysis-logistic regression is successful in assessing additive and multiplicative gene-environment interactions, and in revealing synergistic effects of gene loci rs671 and rs1329149 with alcohol consumption in the pathogenesis and development of colorectal cancer.
    Asian Pacific journal of cancer prevention: APJCP 05/2012; 13(5):2031-7. DOI:10.7314/APJCP.2012.13.5.2031 · 2.51 Impact Factor
  • Source
    • "and CYP2E1 genes show genetic polymorphisms that vary markedly in frequency among different ethnic and racial groups. In most of the studies, these gene polymorphisms have been associated with increased genetic susceptibility to several types of chemical-induced diseases, including several types of cancer related to alcohol consumption (Yokoyama et al., 2002; Brennan et al., 2004; Yang et al., 2009) and alcohol dependence (Edenberg, 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The most well-known metabolic pathways from ethanol to acetaldehyde include alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system that involves cytochrome P450 2E1 (CYP2E1). Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH). The genetic variation of ADH1B, ALDH2, and CYP2E1 is different among racial populations and cause difference in elimination rates of alcohol. The aim of this study was to determine the polymorphisms of ADH1B (rs1229984; Arg47His), ALDH2 (rs671; Glu487Lys), CYP2E1*6 (rs6413432; T7632A), and CYP2E1*7B (rs6413420; G-71T) in unrelated healthy Turkish population and compare it with other populations. ADH1B and ALDH2 polymorphisms were analyzed with an allele-specific polymerase chain reaction (PCR) assay, and CYP2E1*6 and CYP2E1*7B polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. ADH1B polymorphism analysis yielded the genotype distribution as 83.9% ADH1B*1/1 and 16.1% ADH1B*1/2, and no individuals with ALDH2*1/2 and ALDH2*2/2 genotypes were found in Turkish population. The genotype frequencies for CYP2E1*6 polymorphism were found as 85.3% for homozygote common, 14.1% for heterozygote, and 0.6% for homozygote uncommon. For CYP2E1*7B polymorphism, the genotype frequencies were determined to be 86.5% G/G, 13.5% for G/T; however, no individuals with homozygote uncommon genotype were detected. According to our study results, the genotype distributions of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B in Turkish population were similar compared with Caucasian and some European populations, whereas differed significantly from East Asian populations. This study may be useful in epidemiological studies of the influence of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B polymorphisms on diseases, including several types of cancer related to alcohol consumption and alcohol dependence.
    Alcohol (Fayetteville, N.Y.) 08/2010; 44(5):415-23. DOI:10.1016/j.alcohol.2010.06.002 · 2.04 Impact Factor
Show more