Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.     

Loss of Fhit is frequent in stage I non-small cell lung cancer and in the lungs of chronic smokers.

Abnormalities of FHIT, a candidate tumor suppressor gene at 3p14.2, have been found frequently in multiple tumor types including non-small cell lung cancer (NSCLC). To investigate whether FHIT inactivation plays a role in early lung tumorigenesis, Fhit levels were determined by immunohistochemistry in tumors from 87 patients with stage I NSCLC and in 372 bronchial biopsy specimens from 86 chronic smokers without evidence of malignancy. We found that 49% of NSCLC specimens demonstrated significantly decreased staining or lack of staining for Fhit. However, Fhit expression status was not significantly associated with disease-free survival or overall survival. Analysis of a subset of 76 specimens on which microsatellite analysis at the FHIT locus was performed did not show a strong association between loss of heterozygosity at FHIT and Fhit expression, suggesting the presence of complex mechanisms of Fhit inactivation. Of 372 bronchial biopsies from chronic smokers, 86 biopsies (23%) exhibited decreased Fhit expression or lack of Fhit expression. In 37 of 86 (43%) subjects, decreased Fhit expression or lack of expression was observed in at least one biopsy site. Loss of Fhit expression was significantly higher in bronchial metaplastic lesions (23 of 49 lesions, 47%) than in histologically normal bronchial epithelium (63 of 323 specimens, 20%; P < 0.001). Smokers with a metaplasia index of > 15% had a higher frequency of loss of Fhit expression than those with a metaplasia index of < or = 15% (P = 0.015). Interestingly, current smokers had a higher rate of loss of Fhit expression than former smokers (P = 0.02). Our data indicate that Fhit expression is significantly reduced in a substantial number of early-stage NSCLC and preneoplastic lesions in chronic smokers. The association between cigarette smoking and Fhit expression suggests a role for FHIT in the initiation of smoking-related lung tumorigenesis.     

Fumes from meat cooking and lung cancer risk in Chinese women.

Chinese women are recognized to have a high incidence of lung cancer despite a low smoking prevalence. Several studies have implicated domestic exposure to cooking fumes as a possible risk factor, although the exact carcinogens have yet to be identified. Heterocyclic amines are known carcinogens, which have been identified in cooked meat, and also in fumes generated during frying or grilling of meats. We conducted a case-control study of 303 Chinese women with pathologically confirmed, primary carcinomas of the lung and 765 controls to examine the association between exposure to meat cooking and lung cancer risk. Data on demographic background, smoking status, and domestic cooking exposure, including stir-frying of meat, were obtained by in-person interview while in hospital. The response rates among eligible cases and controls were 95.0 and 96.9%, respectively. The proportion of smokers (current or ex-smokers) among cases and controls was 41.7 and 13.1%, respectively. Adenocarcinomas comprised 31.5% of cancers among smokers and 71.6% among nonsmokers. When cases were compared with controls, the odds ratio (OR) for lung cancer (all subtypes) among ex-smokers was 4.3 [95% confidence interval (CI) 2.7-6.8] and that among current smokers was 5.0 (95% CI, 3.4-7.3). Among smokers, women who reported that they stir-fried daily in the past had a significantly increased risk of lung cancer (adjusted OR, 2.0; 95% CI, 1.0-3.8) and among these women, risk was enhanced for those who stir-fried meat daily (OR, 2.7; 95% CI, 1.3-5.5). Women who stir-fried daily but cooked meat less often than daily did not show an elevated risk (OR, 1.0. 95% CI, 0.5-2.4). Risk was further increased among women stir-frying meat daily who reported that their kitchen was filled with oily fumes during cooking (OR, 3.7; 95% CI, 1.8-7.5). These cooking practices on their own did not increase risk among nonsmokers in our study population. Our results suggest that inhalation of carcinogens, such as heterocyclic amines generated during frying of meat, may increase the risk of lung cancer among smokers. Further studies in different settings are warranted to examine this possibility, which may also help to explain the higher risk observed among women smokers compared with men.     

Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus

The FHIT gene, located at chromosome 3p14.2, is a tumor suppressor gene often involved in tumors resulting from exposure to environmental carcinogens. We studied 46 pairs of esophageal primary tumors and corresponding normal squamous mucosa specimens by molecular genetic and immunohistochemical methods to investigate the role of the FHIT gene in esophageal carcinoma. In addition, we studied several different types of lesions, such as carcinoma in situ or dysplasia by immunohistochemistry. Loss of heterozygosity at or around the FHIT gene was observed in 35 (76%) primary tumors. Immunohistochemical detection of Fhit protein in the primary tumors demonstrated that 14 (30%) were positive and 32 (70%) were negative. We observed concordance between loss of Fhit protein and loss of heterozygosity and between loss of Fhit protein and RNA abnormalities. Because the FHIT/FRA3B locus is susceptible to damage by environmental carcinogens, we investigated the correlation between Fhit expression and smoking or alcohol habits. In this relatively small study, the patients who were both heavy users of tobacco and alcohol showed a significantly higher frequency of loss of Fhit expression than those who were light users. Noncarcinomatous squamous epithelium showed positive Fhit reactivity in most cases; however, five showed negative Fhit reactivity. Interestingly, all of these five patients had habits of heavy use of tobacco and alcohol. Eight of 12 carcinomas in situ, 2 of 4 severe dysplasias, 4 of 8 moderate dysplasias, and 3 of 9 mild dysplastic lesions showed negative Fhit reactivity. These findings indicated that loss of Fhit expression may be an early event in the development of human esophageal carcinoma and may occur even in normal-appearing squamous epithelium in some patients heavily exposed to environmental carcinogens.     

Decreased risk of lung cancer in the cotton textile industry of Shanghai

The relationship between lung cancer risk and work in the cotton textile industry was investigated in a large population-based case-control study in urban Shanghai, where the industry is a major employer of men and women. Personal interviews obtained occupational, smoking, and other information from 1405 newly diagnosed lung cancer cases and 1495 controls. A significantly low risk of lung cancer was associated with cotton textile employment [odds ratio (OR) = 0.7,95% confidence interval (CI) = 0.6-0.9]. In men, the decreased risk was observed among both smokers (OR = 0.7, 95% CI = 0.5-1.1) and nonsmokers (OR = 0.3, 95% CI = 0.1-1.0). In women, the risk was also decreased regardless of smoking status (OR = 0.8, 95% CI = 0.4-1.6 among smokers; OR = 0.9, 95% CI = 0.6-1.2 among nonsmokers). In both sexes, the reductions in risk tended to be greater for lung cancer cell types other than adenocarcinoma. Low risks were found regardless of occupations within the cotton textile industry; the OR for workers in textile processing who potentially had greater dust exposure was 0.8 (95% CI = 0.6-1.2), whereas the OR for those in other industry jobs was 0.7 (95% CI = 0.4-1.0). There was little difference in risk according to self-reported exposure to textile dust, and no clear trend with duration of employment or dust exposure. Reasons for the reduced risk of lung cancer in cotton textile workers without a dose response are unclear, although several methodological explanations were considered. The findings, however, appear consistent with prior epidemiological studies and are interesting in light of speculation about tumor-inhibitory factors, such as bacterial endotoxins, that are found in dusts from cotton and other fiber crops.     

Loss of Fhit expression in non-small-cell lung cancer: correlation with molecular genetic abnormalities and clinicopathological features

The FHIT gene is located at a chromosomal site (3p14.2) which is commonly affected by translocations and deletions in human neoplasia. Although FHIT alterations at the DNA and RNA level are frequent in many types of tumours, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of Fhit protein expression with a large number of molecular genetic and clinical parameters in a well-characterized cohort of non-small-cell lung cancers (NSCLCs). Paraffin sections of 99 non-small-cell carcinomas were reacted with an anti-Fhit polyclonal antibody in a standard immunohistochemical reaction. Abnormal cases were characterized by complete loss of cytoplasmic Fhit staining. The Fhit staining results were then correlated with previously obtained clinical and molecular data. Fifty-two of 99 tumours lacked cytoplasmic Fhit staining, with preserved reactivity in adjacent normal cells. Lack of Fhit staining correlated with: loss of heterozygosity (LOH) at the FHIT 3p14.2 locus, but not at other loci on 3p; squamous histology; LOH at 17p13 and 5q but not with LOH at multiple other suspected tumour suppressor gene loci; and was inversely correlated with codon 12 mutations in K-ras. Fhit expression was not correlated overall with a variety of clinical parameters including survival and was not associated with abnormalities of immunohistochemical expression of p53, RB, and p16. All of these findings are consistent with loss of Fhit protein expression being as frequent an abnormality in lung cancer pathogenesis as are p53 and p16 protein abnormalities and that such loss occurs independently of the commitment to the metastatic state and of most other molecular abnormalities.     

Microsomal epoxide hydrolase polymorphisms and lung cancer risk in non-Hispanic whites

Microsomal epoxide hydrolase (mEPHX) is a critical metabolic enzyme involved in the activation and subsequent detoxification of specific tobacco carcinogens. mEPHX harbors polymorphisms in exon 3 and exon 4 that modulate enzymatic activity. The exon 3 polymorphism decreases mEPHX metabolic activity, whereas the exon 4 polymorphism increases activity. We hypothesized that the mEPHX polymorphisms modulate lung cancer risk. Using a case-control study design and restriction fragment length polymorphism polymerase chain reaction assay, we determined the mEPHX polymorphic genotypes of 181 lung cancer cases among non-Hispanic whites and 163 controls (matched for age, sex, ethnicity, and smoking history). Our results showed that the variant allele of mEPHX exon 4 increased the overall lung cancer risk by 56% (odds ratio [OR]=1.56, 95% confidence interval [CI]=0.99-2.46). Additionally, the risk estimates were elevated significantly for younger people (<64 yr) (OR=2.27, 95% CI=1.15-4.50) and current smokers (OR=2.22, 95% CI=1.06-4.65). The variant allele of mEPHX exon 3 had no effect overall (OR=0.88, 95% CI=0.56-1.38), but there was a 53% protective effect (OR=0.47, 95% CI=0.22-0.99) in younger people. When we analyzed the exon 3 and exon 4 polymorphisms together, those people with the high enzymatic activity genotype had an elevated lung cancer risk of 1.72 (95% CI=0.90-3.29). This elevated risk was also evident only in younger people. These findings suggest that these variant alleles of exon 3 and exon 4 of mEPHX modulates lung cancer risk.     

脆性组氨酸三联体与肺癌的临床病理学研究

目的：探讨抑癌基因FHIT在肺癌组织中的表达缺失及其与临床病理因素的关系。方法-采用免疫组织化学S—P法检侧40例肺癌组织中FHIT蛋白表达情况,以癌旁组织作对照。结果：FHIT蛋白表达阴性率在肺癌为65．00％（26／40）,FHIT蛋白在肿瘤组织中的表达明显低于癌旁正常组织（P〈0．05）。其中鳞癌为38．46％（5／13）,腺癌为77．78％（21／27）,其差异有显著性（P=0．01）。FHIT与组织学类型、分化程度及性别有相关性（P〈0．05）。与年龄、肿瘤大小、临床分期、有无淋巴结转移无关（P〉0．05）。结论：FHIT在肺癌中失表达或表达下降可能与肺癌的发生有相关性。     

Dietary heterocyclic amines and the risk of lung cancer among Missouri women

Heterocyclic amines (HCAs) such as 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx,), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are found in meats cooked at high temperatures. In rodents, MeIQx induces lung tumors. The purpose of this study was to investigate lung cancer risk posed by different HCAs in the diet. A population-based case-control study of 593 cases and 623 frequency-matched controls including both nonsmoking and smoking women was conducted in Missouri. An administered food frequency questionnaire with detailed questions on meat consumption, degrees of internal doneness, surface browning/charring, and cooking technique was linked to a database that provided exposure estimates of three HCAs. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. When comparing the 90th and 10th percentiles, significant excess risks were observed for MeIQx (OR, 1.5; CI, 1.1-2.0), but not for DiMeIQx (OR, 1.2; CI, 0.9-1.6) or PhIP (OR, 0.9; CI, 0.8-1.1). MeIQx consumption was associated with increased risk of lung cancer for nonsmokers (OR, 3.6; CI, 1.3-10.3) and light/moderate smokers (OR, 2.1; CI, 1.3-3.3), but not for heavy smokers (OR, 1.0; CI, 0.7-1.5). There was elevated risk with MeIQx intake for subjects with squamous cell carcinomas (OR, 1.9; CI, 1.2-3.1) and "other histological cell types" (OR, 1.6; CI, 1.1-2.5), but not for subjects with small cell carcinomas and adenocarcinomas. Neither DiMeIQx nor PhIP showed an association with smoking categories or lung cancer histology. In conclusion, MeIQx may be associated with lung cancer risk, but DiMeIQx and PhIP are probably not associated with lung cancer risk.     

Lack of interaction between asbestos exposure and glutathione S-transferase M1 and T1 genotypes in lung carcinogenesis.

An interaction between occupational carcinogens and genetic susceptibility factors in determining individual lung cancer risk is biologically plausible, but the interpretation of available studies are limited by the small number of exposed subjects. We selected from the international database on Genetic Susceptibility and Environmental Carcinogens the studies of lung cancer that included information on metabolic polymorphisms and occupational exposures. Adequate data were available for asbestos exposure and GSTM1 (five studies) and GSTT1 (three studies) polymorphisms. For GSTM1, the pooled analysis included 651 cases and 983 controls. The odds ratio (OR) of lung cancer was 2.0 [95% confidence interval (CI) 1.4-2.7] for asbestos exposure and 1.1 (95% CI 0.9-1.4) for GSTM1-null genotype. The OR of interaction between asbestos and GSTM1 polymorphism was 1.1 (95% CI 0.6-2.1) based on 54 cases and 53 controls who were asbestos exposed and GSTM1 null. The case-only approach, which was based on 869 lung cancer cases and had an 80% power to detect an OR of interaction of 1.56, also provided lack of evidence of interaction. The analysis of possible interaction between GSTT1 polymorphism and asbestos exposure in relation to lung cancer was based on 619 cases. The prevalence OR of GSTT1-null genotype and asbestos exposure was 1.1 (95% CI 0.6-2.0). Our results do not support the hypothesis that the risk of lung cancer after asbestos exposure differs according to GSTM1 genotype. The low statistical power of the pooled analysis for GSTT1 genotypes hampered any firm conclusion. No adequate data were available to assess other interactions between occupational exposures and metabolic polymorphisms.     

脆性组氨酸三联体与肺癌的临床病理学研究

目的:探讨抑癌基因FHIT在肺癌组织中的表达缺失及其与临床病理因素的关系.方法:采用免疫组织化学S-P法检侧40例肺癌组织中FHIT蛋白表达情况,以癌旁组织作对照.结果:FHIT蛋白表达阴性率在肺癌为65.00%(26/40),FHIT蛋白在肿瘤组织中的表达明显低于癌旁正常组织(P<0.05).其中鳞癌为38.46%(5/13),腺癌为77.78%(21/27),其差异有显著性(P=0.01).FHIT与组织学类型、分化程度及性别有相关性(P<0.05).与年龄、肿瘤大小、临床分期、有无淋巴结转移无关(P>0.05).结论:FHIT在肺癌中失表达或表达下降可能与肺癌的发生有相关性.     

Smoking and bladder cancer in Spain: effects of tobacco type, timing, environmental tobacco smoke, and gender.

We examined the effects of dose, type of tobacco, cessation, inhalation, and environmental tobacco smoke exposure on bladder cancer risk among 1,219 patients with newly diagnosed bladder cancer and 1,271 controls recruited from 18 hospitals in Spain. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between bladder cancer risk and various characteristics of cigarette smoking. Current smokers (men: OR, 7.4; 95% CI, 5.3-10.4; women: OR, 5.1; 95% CI, 1.6-16.4) and former smokers (men: OR, 3.8; 95% CI, 2.8-5.3; women: OR, 1.8; 95% CI, 0.5-7.2) had significantly increased risks of bladder cancer compared with nonsmokers. We observed a significant positive trend in risk with increasing duration and amount smoked. After adjustment for duration, risk was only 40% higher in smokers of black tobacco than that in smokers of blond tobacco (OR, 1.4; 95% CI, 0.98-2.0). Compared with risk in current smokers, a significant inverse trend in risk with increasing time since quitting smoking blond tobacco was observed (> or =20 years cessation: OR, 0.2; 95% CI, 0.1-0.9). No trend in risk with cessation of smoking black tobacco was apparent. Compared with men who inhaled into the mouth, risk increased for men who inhaled into the throat (OR, 1.7; 95% CI, 1.1-2.6) and chest (OR, 1.5; 95% CI, 1.1-2.1). Cumulative occupational exposure to environmental tobacco smoke seemed to confer increased risk among female nonsmokers but not among male nonsmokers. After eliminating the effect of cigarette smoking on bladder cancer risk in our study population, the male-to-female incidence ratio decreased from 8.2 to 1.7, suggesting that nearly the entire male excess of bladder cancer observed in Spain is explained by cigarette smoking rather than occupational/environmental exposures to other bladder carcinogens.     

Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians.

Reduced DNA repair capacity may influence susceptibility to lung cancer. XRCC1 plays an important role in base excision repair and in rejoining DNA strand breaks. In the XRCC1 gene, two common polymorphisms induce amino acid changes in codon 194 and codon 399 and correlate with levels of genotoxic damage. We examined the relation between these two polymorphisms and susceptibility to lung cancer among 334 incident cases and 704 population controls of African-American and Caucasian ethnicity in Los Angeles County, California. African-American and Caucasian subjects smoking 20+ cigarettes/day and carrying at least one copy of the codon 194 variant allele were at somewhat decreased risk of lung cancer (African-Americans OR=0.2, 95% CI 0.1-0.9; Caucasians OR=0.5, 95% CI 0.2-1.1). Similarly, for the codon 399 polymorphism, there was some evidence of a decreased risk for the homozygous variant genotype among heavier smokers (African-Americans OR=0.3, 95% CI 0.0-2.9; Caucasians OR=0.4, 95% CI 0.2-1.0). These results suggest that genetic variation in XRCC1 might contribute to lung cancer and may interact with the amount smoked.     

Correlation between a single nucleotide polymorphism in the matrix metalloproteinase-2 promoter and risk of lung cancer

Matrix metalloproteinases (MMPs) play an important role in several steps of cancer development. A single nucleotide polymorphism (-1306C-->T) in the MMP2 promoter sequence disrupts an Sp1 site and thus results in strikingly lower promoter activity. We examined the relationship between this polymorphism and risk for lung cancer in 781 cases and 852 age- and sex-matched controls in a Chinese population. We found that the allele frequency of MMP2-1306C was significantly higher among cases than among controls (0.91 versus 0.83). Subjects with the CC genotype had an overall 2-fold increased risk for developing lung cancer [adjusted odds ratio (OR) 2.18; 95% confidence interval (CI), 1.70-2.79] compared with those with the CT or TT genotype. The elevated risk was observed evenly among different subtypes of this cancer. Stratified analysis indicated an additive interaction between the CC genotype and smoking on the elevated risk. The ORs of lung cancer for the CC genotype, smoking, and both factors combined were 2.38 (95% CI 1.64-3.45), 4.26 (95% CI 2.57-8.44), and 7.64 (95% CI 4.74-12.33), respectively. Furthermore, when the data were stratified by the pack-years smoked, this joint effect was more evident and stronger in heavy smokers (OR 10.25, 95% CI 5.80-18.09) than in light smokers (OR 5.55, 95% CI 3.34-9.22). These results demonstrate a significant association between the MMP2 -1306C/T polymorphism and risk of developing lung cancer solely or in a manner of interaction with carcinogen exposure.     

Maternal smoking and testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.     

Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population

Cytochrome P450 2A6 (CYP2A6) plays an important role in the oxidation of nicotine and in the activation of tobacco-related carcinogens, such as N-nitrosodimethylamine, N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. It has been suggested that individuals with defective CYP2A6 alleles are at a lower risk of becoming smokers and of developing lung and other tobacco-related cancers. We examined the relationship between the CYP2A6 gene deletion and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based case-control study. The CYP2A6 gene deletion was determined by a PCR-based approach in 326 healthy controls, 149 patients with esophageal squamous-cell carcinoma and 151 patients with lung cancer. The allele frequency of the CYP2A6*4 deletion was 8.6% among controls compared with 8.4% among cases with esophageal squamous-cell carcinoma (p = 0.29) or 13.2% among cases with lung cancer (p < 0.01). Individuals who harbored at least one CYP2A6*4 deletion allele were at a 2-fold increased risk of developing lung cancer (95% confidence interval [CI] = 1.2-3.2) compared with those without a defective CYP2A6 allele. This effect was mainly limited to squamous-cell carcinoma and to non-smokers, although a joint effect of CYP2A6 deletion and tobacco smoking on lung cancer risk was observed among heavy smokers. The overall risk of esophageal cancer did not appear to be associated with this CYP2A6 genetic polymorphism (odds ratio [OR] = 1.2, 95% CI = 0.7-2.1). However, stratified analysis suggested an excess risk with borderline significance (OR = 2.1; 95% CI = 1.0-4.5) related to the CYP2A6*4 allele among non-smokers. The distribution of CYP2A6 genotype frequency was not significantly different (p = 0.40) between smokers (n = 174) and non-smokers (n = 152) in this study population. Our results demonstrate that the CYP2A6 gene deletion is associated with an increased risk of lung and esophageal cancer but not with a reduced tendency to smoke.     

Glutathione S-transferases as risk factors in prostate cancer.

Glutathione S-transferases are enzymes involved in the metabolism of carcinogens and in the defence against reactive oxygen species. Genetic polymorphisms have been detected in glutathione S-transferases M1, T1 and P1, and some of these polymorphisms have been associated with an increased risk of cancer. In a case-control study (153 cases and 288 controls) the effect of these genetic polymorphisms on the risk of prostate cancer was investigated. Homozygote deletion of either GSTM1 or GSTT1 was not associated with a statistically significant increased risk, odds ratio (OR) 1.3; 95% confidence intervals (CI) 0.9-1.9 and 1.3; 0.8-2.2, respectively. Deletion of both GSTM1 and GSTT1 gave a near-significant increased risk (OR 1.7; 95% CI 0.9-3.4). Two allelic variants of GSTP1 (codon 105) have been reported. This polymorphism was not linked to an increased risk (OR 0.8; 95% CI 0.5-1.1). Smokers that lack either GSTM1 or GSTT1 activity had a slightly higher risk of prostatic cancer than smokers expressing the genes, OR 1.4 (95% CI 0.6-3.3) and 1.6 (0.6-3.9), respectively. Our results show that differences in enzymes involved in the metabolism of carcinogens slightly modify prostate cancer risk, especially in people exposed to carcinogens that are detoxified by these enzymes.