CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals.

The CYP1A1 and glutathione S-transferase enzymes (e.g., GSTM1 and GSTP1) are involved in the activation and conjugation of polycyclic aromatic hydrocarbons (PAHs), respectively, and are controlled by genes that are polymorphic. The CYP1A1*2 allelic variant has been associated with elevated urinary 1-hydroxypyrene (1-OHP), a proposed marker for internal dose of activated PAHs, in coke-oven workers. We investigated whether this association could be observed at low exposure levels, such as those experienced by the general population. We conducted a cross-sectional study among 188 individuals (106 Japanese, 60 Caucasians, and 22 Hawaiians) who were selected as controls in a population-based case-control study and provided lifestyle information, a 12-h urine specimen, and a blood sample. 1-OHP was analyzed by high-performance liquid chromatography after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping. Smokers excreted twice as much 1-OHP (geometric mean, 0.51 nmol/12 h) as nonsmokers (geometric mean, 0.27 nmol/12 h; P = 0.006). Overall and among nonsmokers, 1-OHP urinary levels did not differ by CYP1A1, GSTM1, or GSTP1 genotypes. However, after adjusting for age, ethnicity, and number of cigarettes per day, smokers with at least one CYP1A1*2 variant allele excreted 2.0-fold more 1-OHP than smokers with the wild-type genotype (P = 0.02). Similar results were obtained for the CYP1A1*3 variant allele. The present data add to the growing evidence suggesting that individuals with the (linked) CYP1A1*2 or *3 variant alleles have a greater capacity to activate PAHs from tobacco smoke and occupational exposure and, as a result, are at greater risk for PAH-related cancers, especially certain respiratory cancers.     

CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure

Certain human biotransformation enzymes have been implicated in the formation and scavenging of the ultimate reactive metabolites, the diolepoxides, from polycyclic aromatic hydrocarbons (PAHs). In the present study, performed on aluminum smelter workers, we have analyzed airborne PAH, the pyrene metabolite 1-hydroxypyrene (1-OHP) in urine, and genotypes for biotransformation enzymes involved in PAH metabolism. The aim was to evaluate the correlation between external exposure and biomarkers of exposure and to investigate to what extent genetic polymorphism in metabolic enzymes can explain interindividual variation in urinary 1-OHP levels. DNA was prepared from blood samples from 98 potroom workers and 55 controls and altogether eight polymorphisms in the CYP1A1, mEH, GSTM1, GSTP1 and GSTT1 genes were analyzed. The 1-OHP excretion was found to correlate significantly (P 100-fold) and univariate and multivariate regression analyses were used to find the variables that could determine differences in excretion. The variation could, to some degree, be explained by differences in exposure to airborne particulate-associated PAHs, the use of personal respiratory protection devices, smoking habits and genetic polymorphisms in the cytochrome P450 1A1, GSTM1 and GSTT1 enzymes. The part of the variance that could be explained by differences in biotransformation genotypes seemed to be of the same order of magnitude as the variance explained by differences in exposure. In the control group as well as in the occupationally exposed group, the highest 1-OHP levels were observed in individuals carrying the CYP1A1 Ile/Val genotype who were also of the GSTM1 null genotype. The results show that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that it may also to some extent reflect the interindividual variation in susceptibility to PAHs.     

Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1, GSTM1, and GSTT1, and gastric cancer risk in Korean

Purpose

We investigated the effects of aflatoxin B1 (AFB1) intake, genetic polymorphisms of AFB1 metabolic enzymes, and interactions between the polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in Korean.

Methods

The participants in the study included 477 gastric cancer patients and 477 age- and sex-matched control subjects. Direct interviews and a structured questionnaire were used to determine the level of exposure to AFB1, and the GoldenGate assay and multiplex polymerase chain reaction were used for genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1, epoxide hydrolase 1, and glutathione S-transferase genes.

Results

The probable daily intake of AFB1 was significantly higher among gastric cancer patients than among control subjects (cases vs. controls: 1.91 ± 0.87 vs. 1.65 ± 0.72 ng/kg bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval 1.43–2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not associated with gastric cancer, with the exception of CYP1A2. Moreover, there was no interaction between AFB1 intake and the genotypes of metabolic enzymes that affect gastric cancer risk.

Conclusions

Our results suggest that dietary AFB1 exposure might be associated with a risk of gastric cancer. However, the effect of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms of AFB1 metabolic enzymes.     

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk

Genetic polymorphisms of the genes encoding for the xenobiotic metabolizing enzymes result in individual variations in the efficiency of detoxification of environmental carcinogens, and have been extensively associated with variable risk for lung neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP based assays, we investigated the distribution of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in Greek lung cancer patients (N=122) and healthy controls (N=178). The frequency of CYP1A1 m1 homozygous genotype was 0.04 in patients and 0.02 in controls (detected in 4.10% of patients and in 1.69% of controls, respectively), that of GSTM1 null genotype was 0.52 in patients and 0.54 in controls, whereas those of GSTT1 null genotype was 0.17 and 0.11, in patients and controls, respectively. The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD). The GSTT1 null genotype correlated with advanced age of the patients at the time of diagnosis. Three combinations of rare genotypes - in subjects carrying simultaneously deviations from the common genotype in more than one gene - were over-represented in lung cancer patients, compared to control population, and were furthermore significantly associated with history of heavy tobacco consumption in lung cancer patients. The results imply involvement of specific genotype combinations of CYP1A1, GSTM1 and GSTT1 alleles in the development of lung cancer in heavy smokers.     

CYP1A1, GSTM1, and GSTT1 polymorphisms and breast cancer risk in Brazilian women

The frequency of CYP1A1 (CYP1A1*2A), GSTM1, and GSTT1 polymorphisms, as well as the main risk factors associated with breast cancer were studied in Brazilian women, with malignant breast cancer (n=128), or age-matched controls (n=256). Only a family history of breast cancer presented a significant risk (OR=3.00, CI=1.27-7.06). Among non-whites, the CYP1A1*2A allele was underrepresented among patients. Statistical analysis indicated that this polymorphism may decrease the risk of breast cancer among these individuals, particularly after adjusting for the risk presented by selected risk factors (OR=0.30, 95% CI=0.12-0.76).     

Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1: relation to the incidence rate of cervical carcinoma

BACKGROUND: The authors established the genotype frequencies of cytochrome P450 (CYP1A1/MspI, CYP2E1/PstI, and CYP2E1/DraI), glutathione-S-transferase (GSTM1 and GSTT1), and p53 (exon 4/AcclI and intron 3/16-base pair duplication) gene polymorphisms in cervical carcinoma patients and controls and evaluated the association between the specific genotype or genotype combinations of these polymorphisms and the risk of cervical carcinoma. METHODS: In this case-control study, the genotypes of 181 human papillomavirus (HPV)-16 or HPV-18 positive cervical carcinoma patients and 1-to-1 age-matched controls were determined using a polymerase chain reaction-based technique. RESULTS: Among these polymorphisms, the individuals carrying arginine/proline genotypes of p53 showed a 9.5-fold increase of cervical carcinoma risk (95% confidence interval [CI], 4.9-18.6) compared with those individuals carrying arginine/arginine genotypes. The frequency of overall GSTT1 null genotypes also was significantly higher in cervical carcinoma patients compared with that of GSTT1 positive genotypes (P = 0.003; odds ratio [OR] = 1.9; 95% CI, 1.2-2.9). The genotype combination of p53 and GST played a more important role in describing the relative risk of cervical carcinoma. The individuals carrying both the arginine/proline genotype of p53 and the null genotype of GSTT1 showed a 3.5-fold increase of cervical carcinoma risk (95% CI, 1.8-7.1) compared with those individuals carrying both the arginine/arginine genotype of p53 and the GSTT1 positive genotype. In the patients who were stratified into the two age groups, the null genotypes of GSTT1 (69.1% vs. 45.5%; P = 0.016) and GSTM1 (61.8% vs. 40.0%; P = 0.028) in cervical carcinoma were significantly overrepresented in the younger age subgroup (age 40 years or younger) compared with those of controls. Especially in this age group, the individuals carrying both null genotypes of GSTT1 and GSTM1 showed a 17.8-fold increase of cervical carcinoma risk (95% CI, 2.2-141.0) compared with the individuals carrying both positive genotypes of GSTT1 and GSTM1. CONCLUSIONS: The results of the current study suggested that the arginine/proline genotype of p53, independently or in conjunction with the GSTT1 null genotype, could affect the genetic susceptibility for cervical carcinoma, and HPV positive women carrying both null genotypes of GSTT1 and GSTM1 have an increased risk of cervical carcinoma developing before age 40 years.     

Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: a case-control study in the Grampian region of Scotland

Cytochrome P-450 CYP1A1 is involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs) that are derived from meat intake and tobacco smoking. Expression of the CYP1A1 gene is induced by compounds present in cruciferous vegetables. The glutathione S-transferases play a central role in the detoxification of carcinogens, including PAHs. We investigated the association between colorectal cancer and three variants (CYP1A1*2A, CYP1A1*2C, CYP1A1*4) of the CYP1A1 gene, and homozygosity for the null deletion of the GSTM1 and GSTT1 genes, and the joint effects of these genotypes and smoking, meat intake and intake of green leafy vegetables in a population-based study of 264 cases and 408 controls in Northeast Scotland. There was an inverse association with the CYP1A1*4 (m4) variant (OR 0.3, 95% CI 0.13-0.70). The OR for the CYP1A1*2C (m2) variant was 1.3 (95% CI 0.59-2.91), which is similar to a combined estimate for previous studies (OR 1.2, 95% CI 0.95-1.41). We observed no association with the CYP1A1*2A (m1) variant, or the GSTM1 and GSTT1 polymorphisms. Significant interactions between all 3 CYP1A1 variants and meat intake, and between the m1 and m2 variants and intake of green leafy vegetables, were observed. There was no evidence of interaction between CYP1A1 and smoking, and no evidence of interaction between the GSTM1 or GSTT1 polymorphisms and smoking, meat intake, green leafy vegetable intake, CYP1A1 variants or each other.     

Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: a case-control study in Chinese population

A case-control study of 164 lung adenocarcinoma (AC) patients with 181 age- and gender-matched healthy controls was conducted in order to assess any associations between glutathione- S -transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cyto-chrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp 1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340–0.837)]. Furthermore, 3.0-fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa 1 wild type versus those with combined GSTM1 non-null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa 1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC. (Cancer Sci 2003; 94: 448–452)     

CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people.

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(-) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(-). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR=6.28; m2/GSTM1(-), OR=3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/C, OR=1.39; m2/c2, OR=2.00; val/C, OR=1.45; val/c2, OR=0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(-), 7.38 for m2/val and 3.68 for m2/GSTM1(-), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.     

Ethnic susceptibility to lung cancer: differences in CYP2E1, CYP1A1 and GSTM1 genetic polymorphisms between French Caucasian and Chilean populations.

Many investigators have reported an association between genetic polymorphisms of cytochromes P-450 CYP2E1, CYP1A1 or glutathione S-transferase Mu (GSTM1) and susceptibility to lung cancer. However, pronounced interethnic variations have been described in the frequencies of these polymorphisms, especially between Asians and Caucasians. The present study was set up to establish CYP2E1 (c1, c2 and C, D), CYP1A1 (m1, m2 and Ile, Val) and GSTM1 (null) allelic frequencies in Chileans (n = 96) who are an admixture of Native Americans and Caucasians (Spaniards). The rare allele frequencies were found to be 0.15 (c2), 0.21 (C), 0.23 (m2), 0.32 (Val) and 0.21 ('null' genotype). These values are significantly higher than those of Caucasians except for the GSTM1 'null' genotype and suggest differences in susceptibility to lung cancer between both populations.     

CYP2E1 、 GSTT1 、GSTM1基因型与食管癌关系

[目的]研究CYP2E1Rsa1,Rsa I,GSTT1,GSTM1基因多态性和烟酒茶嗜好及其相作作用与食管癌刎感性的关系。[方法]在食管癌高发区淮安市进行了一个病例对照组研究（食管癌144例,人群对照233例）,调查地象的烟酒茶嗜好习惯,以PCR扩增,Rsa,I内切酶消化,分析CYP2E1的基因型,以多重PCR驻京GSTT1,GSTM1基因型,[结果]（1）对照组GSTM1基因型频度及饮茶状况分布与食管癌组之间存在显著差异。携带GSTM1正常基因型或有饮茶习惯者发生食管癌的危险性显著降低。（2）在不同烟酒茶嗜好者中,CYP2E1,GSTT1和GSTM1基因型对食管癌发生的影响有所不同。[结论]（1）携带GSTM1正常基因型或饮茶能降低食管癌发生的危险性。（2）在食管癌发生中存在环境因素与遗传因素的相互作用。     

Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk

Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. ITCs down-regulate cytochrome P-450 biotransformation enzyme levels, activate Phase II detoxifying enzymes and induce apoptosis. On the other hand, ITCs also serve as a substrate for GSTs. Experimental evidences suggest that ITCs have anticarcinogenic effect on bladder cancer. Therefore, we evaluated dietary intake of ITCs, GSTM1, GSTT1 and NAT2 polymorphisms, and bladder cancer risk in a case-control study. There were 697 newly diagnosed bladder cancer cases identified from The University of Texas M. D. Anderson Cancer Center and 708 healthy controls matched to cases by age (+/-5), gender and ethnicity. Participants underwent an in-person interview, in which epidemiologic and food frequency questionnaires were administered to collect demographic and dietary intake data. Median ITC intake per day was statistically significantly lower in cases than in controls (0.23 vs. 0.33, p < 0.001). High ITC intake was associated with 29% decreased risk of bladder cancer [Odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.57, 0.89]. The protective effect was more evident in older individuals (> or =64-years-old), men, ever smokers and heavy smokers in stratified analysis. Compared with NAT2 rapid acetylator, NAT2 slow acetylator had an increased risk of bladder cancer in Caucasians (OR = 1.31, 95% CI = 1.02, 1.69). There was no main effect associated with the GSTM1 or GSTT1 genotypes. The protective effect of ITCs against bladder cancer was not modified by GSTM1, GSTT1 or NAT2 genotypes. This is the first epidemiological report that ITCs from cruciferous vegetable consumption protect against bladder cancer.     

Association of GSTM1, GSTT1, GSTP1 and CYP2E1 Single Nucleotide Polymorphisms with Colorectal Cancer in Iran

Colorectal cancer is a major cause of morbidity and mortality both globally and in Iran. The aim of this study was to determine the association between genetic polymorphisms of glutathione S-transferases P1, M1 and T1 (GSTP1, M1, T1) and susceptibility to colorectal cancer (CRC). Genotyping of GSTP1, GSTM1 and GSTT1 was performed by the use of pyrosequencing. One hundred cases and healthy controls were enrolled into this study. Mean GSTT1 polymorphism type was significantly (P < 0.01) higher in cases as compared to controls (P < 0.0001: OR, 2.43: 95% CI, 1.47-4). On the other hand there is no significant association between GSTM1, GSTP1 and colorectal cancer. GSTs measurement may be useful as a colorectal marker in colorectal cancer and biopsies obtained at colonoscopy can be used to measure tumor markers.     

GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk

Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In this study we investigated GSTM1, GSTT1 and GSTP1 status in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. Cases were all patients (n=94) currently with, or with a history of, tumours of the lung, trachea or bronchus. The control group were all other patients (n=165) who were free of benign and malignant tumours both at the time of, or prior to, diagnosis. All patients were interviewed for information on lifestyle risk factors, and DNA extracted from bronchial lavage and blood samples was used for genotyping. GSTM1 null genotype was associated with decreased lung cancer risk (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.29–0.87), particularly among men (OR 0.43, 95% CI 0.21–0.87) and those above the median age (OR 0.33, 95% CI 0.15–0.70). No difference in GSTT1 and GSTP1 genotype distribution was seen between cases and controls. The GSTM1 null genotype was associated with a decreased risk of squamous cell carcinoma: the OR, adjusted for age, sex and pack years was 0.32 (95% CI 0.12–0.82). As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.     

Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator

Oral cancer is the leading cancer type among Southeast Asianmen and is causally associated with the use of tobacco. Geneticpolymorphisms in xenobiotic-metabolizing enzymes modify theeffect of environmental exposures, thereby playing a significantrole in gene–environment interactions and hence contributeto the high degree of variance in individual susceptibilityto cancer risk. This study investigates the role of polymorphismsat CYP1A1, GSTM1 and GSTT1 to oral squamous cell carcinoma (OSCC)in a case–control study involving 155 patients with precancerouslesions, 458 cancer patients and 729 age and habit-matched controls.Genotypes at these loci were determined by polymerase chainreaction (PCR) and PCR-restriction fragment length polymorphismperformed on genomic DNA extracted from peripheral blood lymphocytes.Risk to oral cancer was estimated among different tobacco exposuregroups and doses using logistic regression analysis. GSTM1 nullgenotype conferred 1.29-fold increased risk [95% confidenceinterval (CI), 1.04–1.65] to OSCC. GSTT1 null genotype,however, conferred 0.57 times reduced risk to OSCC (95% CI,0.39–0.83), specifically among tobacco chewers (odds ratio0.27; 95% CI, 0.14–0.53). This risk was further reducedto 0.13 times (95% CI, 0.04–0.46) with increase in lifetimeexposure to tobacco. We also investigated risk conferred bythese genotypes at two different intra-oral sites, buccal mucosaand tongue. We found increased susceptibility to buccal mucosacancer among individuals carrying these genetic markers. Theseresults support the finding that GSTM1 null genotype is a riskfactor to OSCC among Indian tobacco habits; GSTT1 null genotype,however, emerged as a protective factor. Abbreviations: CI, confidence interval; CYP, cytochrome p450; GSH, glutathione; GST, glutathione S-transferase; OR, odds ratio; OSCC, oral squamous cell carcinoma; PAH, polycyclic aromatic hydrocarbon; PCL, precancerous lesion; PCR, polymerase chain reaction; SCE, sister chromatid exchange Received October 18, 2006; revised February 8, 2007; accepted February 11, 2007.     

Influence of CYP1A1, CYP2E1, GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: results from a case-control study in Rio de Janeiro

Xenobiotic metabolizing enzymes are involved in the detoxification of many carcinogens and may be important in modulating cancer susceptibility. CYP1A1, CYP2E1, GSTM3, and NAT2 polymorphisms were determined in peripheral blood DNA of 231 oral cancer patients and 212 hospital controls in Rio de Janeiro, Brazil, using the PCR-RFLP technique. NAT2 polymorphism distribution was different between cases and controls (P=0.035), with an overrepresentation of NAT2( *)11 mutant allele in controls. Risk analysis showed that NAT2 4/4 individuals (OR=1.95, 95% CI=1.05-3.60) and combined GSTM3 and NAT2 heterozygotes (OR=1.94, 95% CI=1.04-3.66) were at increased oral cancer risk. No statistically significant association was observed for CYP1A1 and CYP2E1 polymorphisms. Our results suggest that NAT2 polymorphism, alone or combined with GSTM3, may modulate susceptibility to oral cancer in Rio de Janeiro.     

Polymorphisms in GSTM1, GSTT1 and CYP1A1 and risk of pancreatic adenocarcinoma

A prospective study of 149 unselected incident cases of pancreatic adenocarcinoma and 146 ethnically-matched controls found no associations between GSTM1 (adjusted odds ratio (AOR) 1.14), GSTT1 (AOR: 1.19) and CYP1A1 (AOR: 1.08) polymorphisms and pancreatic cancer susceptibility. Smoking and drinking status did not affect results. These polymorphisms do not appear to be important gene modifiers in pancreatic cancer.     

CYP1A1 CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus

We investigated the genetic polymorphisms of CYPIAI, CYP2EI and GSTMI in Japanese esophageal cancer patients (n = 53) with a histological diagnosis of squamous-cell carcinoma, to determine whether susceptibility to esophageal cancer is associated with these polymorphisms. There were no significant differences in the frequency distribution of any one of the 3 polymorphisms between esophageal cancer patients and 132 healthy Japanese controls. The genotype distributions in tobacco smokers or alcohol drinkers were also quite similar for male patients and male controls. The age at onset of esophageal cancer was also similar for patients with any genotype of the 3 polymorphisms. We conclude that the 3 polymorphisms are unlikely to be associated with esophageal cancer susceptibility. Int. J. Cancer 71:192–195, 1997. © 1997 Wiley-Liss, Inc.