Carcinogenesis

This Article Abstract FREE Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (97) Request Permissions Google Scholar Articles by Benhamou, S. Articles by Taioli, E. Search for Related Content PubMed PubMed Citation Articles by Benhamou, S. Articles by Taioli, E. Social Bookmarking          What's this?

Carcinogenesis, Vol. 23, No. 8, 1343-1350, August 2002
© 2002 Oxford University Press

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk

Simone Benhamou^1,27, Won Jin Lee², Anna-Karin Alexandrie³, Paolo Boffetta², Christine Bouchardy⁴, Dorota Butkiewicz⁵, Jurgen Brockmöller⁶, Margie L. Clapper⁷, Ann Daly⁸, Vita Dolzan⁹, Jean Ford¹⁰, Laura Gaspari¹¹, Aage Haugen¹², Ari Hirvonen¹³, Kirsti Husgafvel-Pursiainen¹³, Magnus Ingelman-Sundberg³, Ivan Kalina¹⁴, Masahiro Kihara¹⁵, Pierre Kremers¹⁶, Loïc Le Marchand¹⁷, Stephanie J. London¹⁸, Valle Nazar-Stewart¹⁹, Masako Onon-Kihara²⁰, Agneta Rannug³, Marjorie Romkes²¹, David Ryberg¹², Janeric Seidegard²², Peter Shields²³, Richard C. Strange²⁴, Isabelle Stücker²⁵, Jordi To-Figueras²⁶, Paul Brennan² and Emanuela Taioli¹¹

¹ INSERM U521, EMI 00–06, Evry, France,
² International Agency for Cancer Research, Lyon, France,
³ Karolinska Institutet and National Institute for Working Life, Stockholm, Sweden,
⁴ Geneva Cancer Registry, Switzerland,
⁵ Centre of Oncology, Gliwice, Poland,
⁶ Georg-August-University, Göttingen, Germany,
⁷ Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA,
⁸ University of Newcastle, UK,
⁹ University of Ljubljana, Slovenia,
¹⁰ Columbia College of Physicians and Surgeons, New York, USA,
¹¹ Ospedale Maggiore IRCCS, Milan, Italy,
¹² National Institute of Occupational Health, Oslo, Norway,
¹³ Finnish Institute of Occupational Health, Helsinki, Finland,
¹⁴ P.J. Safarik University, Kosice, Slovakia,
¹⁵ Kyoto University School of Public Health, Kyoto, Japan,
¹⁶ Institut de Pathologie, Liège, Belgium,
¹⁷ University of Hawaii, Honolulu, Hawaii USA,
¹⁸ National Institute for Environmental Health Sciences, Research Triangle Park, North Carolina, USA,
¹⁹ Oregon Health Sciences University, Oregon, USA,
²⁰ Nagasaki University Graduate School of Medicine, Nagasaki, Japan,
²¹ University of Pittsburgh, Pennsylvania, USA,
²² Lund University, Lund, Sweden,
²³ Georgetown University Medical Center, Washington, DC, USA,
²⁴ Keele University, Staffordshire, UK,
²⁵ INSERM U170, Villejuif, France and
²⁶ Hospital Clinic Provincial, Barcelona, Spain

	Abstract

Top Abstract Introduction Materials and methods Results Discussion References

 
Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07–1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98–1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.

Abbreviations: CI, confidence interval; GST, glutathione S-transferase; OR, odds ratio

	Introduction

Top Abstract Introduction Materials and methods Results Discussion References

 
Numerous tobacco carcinogens are activated or detoxified by xenobiotic metabolizing enzymes (XMEs). Inherited differences in the XME-related metabolic capacity are potentially important sources of inter-individual variation in the susceptibility to development of smoking-related cancers. To date, five glutathione S-transferases (GSTs) classes have been described in humans, of which enzymes belonging to three of the classes, i.e. GST-M (µ) class, GST-P () class and GST-T () class, are involved in the detoxification of electrophilic metabolites of several potential carcinogens present in tobacco smoke, including benzo[a]pyrene and other polycyclic aromatic hydrocarbons (1). The homozygous deletion of GSTM1 gene (null genotype) results in a total lack of enzyme and is present in 50% of Caucasian and Asian populations, and 25% of African populations (Garte et al., personal communication). It is therefore conceivable that carriers of the null genotype are at increased risk of lung cancer because of a reduced ability to detoxify environmental carcinogens.

The association between GSTM1 polymorphism, determined by genotyping methods, and lung cancer has been investigated in numerous epidemiological studies. Two recent meta-analyses of case-control studies which had been published until May 1997 (2) and for the years 1985–1998 (3), suggested an association between GSTM1 null genotype and lung cancer; the risks seemed to be higher among Asians and for squamous cell and small cell carcinomas (4). Since these overviews, at least 15 additional case-control studies have examined the relationship of GSTM1 genotype and lung cancer. We have therefore undertaken a new meta-analysis to summarize the results of 43 published studies. Because the GSTM1 genotype is presumed to affect lung cancer risk by influencing detoxification of activated tobacco carcinogens, the potential modifying effect of GSTM1 genotype on the relationship between tobacco smoking and lung cancer is of particular interest. Differences in associations for the GSTM1 null genotype by level of smoking were investigated in some previous studies; however, the statistical power to detect them was generally limited. We therefore investigated the role of GSTM1 genotype as a modifier of the effect of smoking exposure on lung cancer risk in a pooled analysis of individual data from 21 separate studies provided to the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) (5).

	Materials and methods

Top Abstract Introduction Materials and methods Results Discussion References

 
Data collection
A literature search for case-control studies on the association between lung cancer and GSTM1 genotype was conducted using citations in two previous review articles (2,3). For a given study, we retained the most recent results in the case of more than one publication on approximately the same data set. When results of a study were stratified by ethnicity, we treated data of each ethnic group as separate studies. A total of 20 genotype-based case-control studies were identified. We did not retain one study (6) because of outlying results [odds ratio (OR) = 6.7, 95% confidence intervals (CI) 3.0–15.3].

A search using MEDLINE was conducted to identify additional studies published before February 2001, without restriction on language. The results of this search brought the total number of published case-control studies to 43, with a total of 7463 lung cancer patients and 10 789 control individuals (see Appendix for details of individual studies).

View this table: [in this window] [in a new window]   Appendix Summary of the 43 published case-control studies of lung cancer and GSTM1 genotype included in the meta-analysis

 
Furthermore, we used the original data of 21 case-control studies on GSTM1 genotype and lung cancer, with a total of 3940 lung cancer patients and 5515 controls, which were provided by the investigators to the GSEC study, a collaborative project investigating the relationships of several genetic polymorphisms and cancers at different sites (5). Investigators who had previously published case-control studies up to June 2000 were identified through MEDLINE. They were contacted by letter and asked to provide published or unpublished original data on all subjects included in their study(s). The results were published (or partly published) for 17 of the 21 studies on lung cancer and GSTM1 genotype and unpublished for the four remaining studies. For some of the studies, the number of subjects or of genotypes tested provided to the GSEC database differed slightly from those in the published reports.

Statistical analyses
Crude ORs and their 95% CIs associated with GSTM1 null genotype were estimated for each individual study. Meta-analytic techniques that weight the logarithm of the OR of each study by a function of its variance were used to calculate a summary estimate. Both fixed- and random-effects models were used and results of the latter are presented in case of heterogeneity between studies, defined as Q-statistics with P < 0.05 (7). Meta-analyses were performed on the total data set and separately for the major ethnic groups, and after restriction to studies involving population controls. Results of meta-analyses may be biased if not all available studies are included (8). We assessed potential publication bias (tendency for authors to submit or of journals to accept preferentially papers reporting an association over papers reporting no association) by examining funnel plots (9) and using Egger’s test (10). This statistical test detects whether the intercept deviates significantly from zero in a regression of the standardized effect estimates against their precision.

Individual data of lung cancer patients and controls included in the GSEC database were used to investigate the potential modifying effect of GSTM1 genotype on the relationship between smoking and lung cancer, and to test if the association between GSTM1 and lung cancer varies with histology, ethnicity or gender. Individuals were categorized as never- versus ever-smokers; for ever-smokers, smoking exposure was further categorized as <20, 20–39 and 40 pack-years (years smoked times the packs of cigarettes/day) according to the tertile distribution in the control population. Analyses were conducted using unconditional logistic regression models taking into account the potential confounding effects of age (in tertiles), gender, and center on the pooled data set, and after stratification by lung cancer histology, ethnicity and gender; however, the sample sizes were large enough on cross-classification to allow these analyses only for squamous cell carcinoma, small cell carcinoma and adenocarcinoma, and for Caucasian and Asian individuals. Individuals with the GSTM1 present genotype were used as reference category in each category of smoking exposure. Statistical analyses were performed using STATA software (version 6.0).

	Results

Top Abstract Introduction Materials and methods Results Discussion References

 
The ethnicity of cases and controls was detailed in 40 of the studies; most of the subjects in the pooled data set were either Caucasians (55%) or Asians (25%) (Table I). Individual study results of lung cancer risk associated with GSTM1 null genotype are presented in Figure 1. An OR above 1 was found in 31 studies, but the increase in risk was statistically significant in only five of them. The summary OR generated by all the 43 published case-control studies suggested a weak association between GSTM1 null genotype and lung cancer (OR = 1.17, 95% CI 1.07–1.27), but the estimates lacked homogeneity (P = 0.007) (Table I). Stratification by ethnicity showed lack of heterogeneity in the estimates for Caucasians (20 studies, P = 0.5, summary OR = 1.10, 95% CI 1.01–1.19) and heterogeneity for Asians (12 studies, P = 0.001, summary OR = 1.33, 95% CI 1.06–1.67). No significant associations were found in other ethnic groups (Table I). We found no evidence of publication bias based on Begg’s funnel plot (Figure 2) and Egger’s tests on all studies (P = 0.4), or separately for Caucasian (P = 0.8) or Asian (P = 0.7) populations (funnel plots not shown). Additional analyses on 14 studies published in 1999–2000 and not included in the previous overviews yielded a OR = 1.16 (95% CI 1.00–1.33); heterogeneity in the estimates was of borderline significance (P = 0.056).

View this table: [in this window] [in a new window]   Table I. Results of meta-analyses of lung cancer risk associated with GSTM1 null genotype

 

View larger version (33K): [in this window] [in a new window]   Fig. 1. ORs (95% CI) of lung cancer associated with GSTM1 null genotype. Results of meta-analysis of 43 published case-control studies. Note: the study by Saarikoski et al. (17) was published on 208 cases and 294 controls (OR = 1.06, 95% CI 0.73–1.54); 138 lung cancer cases included in a previous study (29) were removed from the present analysis.

 

View larger version (11K): [in this window] [in a new window]   Fig. 2. Begg’s funnel plot with 95% CIs of studies on lung cancer and GSTM1 genotype.

 
Selected characteristics of the 21 case-control studies from the GSEC database used to assess the association between GSTM1 genotype and lung cancer across groups of individuals with different smoking exposures are shown in Table II. Substantial amounts of data were available for studies including population controls and for Caucasian individuals (78 and 77% of the pooled data set, respectively). Information on age was provided for 99% of lung cancer patients (mean age ranged from 54–69 years) and 89% of controls (mean age ranged from 36–66 years). Data on smoking status (ever/never) was available for 91% of cases and 82% of controls, and information on pack-years was provided for the majority of ever-smokers (93% of cases and 86% of controls). Smoking was a matching criterion in some studies or was not available in other studies; we were therefore unable to properly examine the associations between lung cancer and smoking in the total database. Logistic regression analysis restricted to studies without selection on smoking habits and with available information on smoking (11,12,13–15,16–22; unpublished data from Clapper et al. and Romkes et al.) yielded, as expected, a significant increase in lung cancer risks with increasing levels of smoking: compared with never-smokers, the risk estimates were 5.50 (95% CI 4.17–7.26) for smokers of 20 pack-years, 22.29 (95% CI 17.00–29.22) for smokers of 20–39 pack-years and 35.01 (95% CI: 26.76–45.79) for smokers of 40 pack-years.

View this table: [in this window] [in a new window]   Table II. Characteristics of the 21 case-control studies included in the GSEC database

 
Analyses on the total set of 21 studies in the GSEC database revealed no evidence for increased risk of lung cancer among carriers of GSTM1 null genotype (age-, sex- and center-adjusted OR = 1.08, 95% CI 0.98–1.18) overall or separately for Caucasians (OR = 1.03, 95% CI 0.93–1.14) or Asians (OR = 1.09, 95% CI 0.82–1.45) (Table III). Risk estimates from the pooling of individual data were similar for published (OR = 1.08, 95% CI 0.98–1.18) and unpublished (OR = 1.06, 95% CI 0.79–1.43) studies. Restriction to studies with population controls or hospital controls yielded OR = 1.08 (95% CI 0.97–1.21) and OR = 1.03 (95% CI 0.86–1.23), respectively.

View this table: [in this window] [in a new window]   Table III. ORa of lung cancer (95% CI) associated with GSTM1 null genotype according to smoking status (GSEC database)

 
Adjusted lung cancer risks associated with the GSTM1 genotype according to smoking status are shown in Table III. We found no evidence of interaction between GSTM1 genotype and smoking status. Relative to the GSTM1 positive genotype, the OR for the GSTM1 null genotype were 1.09 (95% CI 0.84–1.42) among never-smokers and 1.09 (95% CI 0.98–1.22) among ever-smokers. Further categorization of smokers by lifetime tobacco consumption (Table IV) did not produce any appreciable increase in risks for carriers of GSTM1 null genotype: OR = 0.94 (95% CI 0.74–1.21) for smokers of 20 pack-years, OR = 1.21 (95% CI 0.97–1.50) for smokers of 20–39 pack-years, and OR = 1.20 (95% CI 1.00–1.45) for smokers of 40 pack-years (Table IV). Likewise, stratification by sex, histology (squamous cell, small cell or adenocarcinoma) or ethnicity (Caucasians or Asians) did not reveal differences in risks associated with GSTM1 genotypes (Table IV).

View this table: [in this window] [in a new window]   Table IV. ORsa of lung cancer (95% CI) associated with GSTM1 null genotype according to smoking exposure (GSEC database)

 

	Discussion

Top Abstract Introduction Materials and methods Results Discussion References

 
GSTM1 null genotype conferred a 1.17-fold statistically significant increased risk of lung cancer in our meta-analysis of 43 published case-control studies involving >18 000 subjects. Our findings are consistent with the summary meta-analysis ORs of 1.13 and 1.20 reported by Houlston (3) and Vineis et al. (4), respectively. They also suggest that the association might be stronger among Asians. Results of meta-analyses may depend on control selection procedures; however, restriction of the analyses to studies with population controls did not materially alter the present observations on association between the GSTM1 genotype and lung cancer. Meta-analysis based on only published reports will yield biased results if publication bias is operating (8). In the absence of publication bias, funnel plot will resemble a symmetrical inverted funnel. In our analyses, both the funnel plots and statistical tests, although not very powerful, suggest absence of substantial publication bias. However, it is not easy to estimate the extent of publication bias and we cannot rule out that such bias could explain the slight excess risk of lung cancer observed in our meta-analysis.

Lung cancer risk was not significantly associated with GSTM1 null genotype in our analyses of individual data of a subset of 21 case-control studies. Meta-analyses of published results and pooled analyses of original data have advantages and limitations. More valid and precise conclusions regarding a particular exposure–disease relation are expected in pooled analyses because of use of common definitions, coding, cut-points for variables and adjustment for the same confounders. Given that adjustment for age, sex and center was included in the present pooled analysis, it is probable that our results, if anything, are only modestly confounded by these factors. However, other genetic factors (e.g. CYP1A1 genetic polymorphisms), not taken into account in our analyses, may confound the association between lung cancer and GSTM1 genotype. Errors in assigned GSTM1 genotype may also bias the risk estimates; as long as this misclassification is non-differential with respect to case-control status, the bias is toward the null. Frequencies of GSTM1 null genotype in the controls of the major ethnic groups were consistent with that estimated in a very large control series (Garte et al., personal communication), which however comprises our controls. It seems also unlikely that the lack of association between GSTM1 polymorphism and lung cancer may be due to differential misclassifications in GSTM1 genotype among cases and controls. Further analyses were also performed for comparison of results from the 14 studies included in both the meta-analysis and the pooled analysis (11,12,13–21,23–25). The lung cancer risk associated with the GSTM1 null genotype was higher, although not significantly, in the meta-analysis (OR = 1.12, 95% CI 1.02–1.24) than in the pooled analysis (OR = 1.05, 95% CI 0.96–1.16). Control for the effects of age and gender could explain the attenuated lung cancer risk estimate observed in the pooled analysis.

The large amount of available data on smoking-related variables in the GSEC database (87% of all subjects) allowed us to study the potential modifying effect of GSTM1 genotype on the relationship between tobacco smoking and lung cancer. In the pooled analysis of 21 studies, we found no evidence of interaction between GSTM1 genotype and either smoking status or smoking consumption. Analyses of gene–environment interactions raise concerns about adequate statistical power. To date, most of the reported studies on lung cancer had limited power to detect interactions between GSTM1 polymorphism and smoking. In the present analyses, based on over 9000 individuals, we had 80% power to detect an OR for interaction of between 1.5 and 1.6, based on an OR of 10.0 for ever smoking, and an OR of 1.2 for having the GSTM1 null genotype (26). Therefore, lack of differences in risks associated with GSTM1 genotypes across categories of smoking are likely not explained by insufficient power.

In the present study, GSTM1 genotype did not appear to interact with smoking; however, it is possible that gene–gene interactions (e.g. between different types of GSTs) and interactions between genes and other environmental factors may play a role. For instance, recent data from studies in China (27) and the US (28) suggest that dietary isothiocyanates may modify the effect of GSTM1, which catalyzes the rapid elimination of these beneficial compounds. Few of the published studies contain dietary information and thus we were not able to consider this potential diet–gene interaction.

	Notes

 
²⁷ To whom correspondence should be addressed Email: benhamou{at}evry.inserm.fr

	References

Top Abstract Introduction Materials and methods Results Discussion References

 

1. Hayes,J.D. and Pulford,D.J. (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol., 30, 445–600.[ISI][Medline]
2. d’Errico,A., Malats,N., Vineis,P. and Boffetta,P. (1999) Review of studies of selected metabolic polymorphisms and cancer. In Vineis,P., Malats,N., Lang,M., d’Errico,A., Caporaso,N., Cuzick,J. and Boffetta,P. (eds), Metabolic Polymorphisms and Susceptibility to Cancer. IARC Scientific Publications, Vol. 148, IARC, Lyon, France.
3. Houlston,R.S. (1999) Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis. Cancer Epidemiol. Biomark. Prev., 8, 675–682.[Abstract/Free Full Text]
4. Vineis,P., d’Errico,A., Malats,N. and Boffetta,P. (1999) Overall evaluation and research perspectives. In Vineis,P., Malats,N., Lang,M., d’Errico,A., Caporaso,N., Cuzick,J. and Boffetta,P. (eds), Metabolic Polymorphisms and Susceptibility to Cancer. IARC Scientific Publications, Vol. 148, IARC, Lyon, France.
5. Taioli,E. (1999) International collaborative study on genetic susceptibility to environmental carcinogens. Cancer Epidemiol. Biomark. Prev., 8, 727–728.[Free Full Text]
6. Baranov,V.S., Ivaschenko,T., Bakay,B. et al. (1996) Proportion of the GSTM1 0/0 genotype in some Slavic populations and its correlation with cystic fibrosis and some multifactorial diseases. Hum. Genet., 97, 516–520.[ISI][Medline]
7. DerSimonian,R. and Laird,N.M. (1986) Meta-analysis in clinical trials. Control. Clin. Trials, 7, 177–188.[ISI][Medline]
8. Greenland,S. (1998) Meta-analysis. In Rothman,K.J. and Greenalnd,S. (eds), Modern Epidemiology. Lippincott-Raven, Philadelphia.
9. Begg,C.B. and Mazumbar,M. (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088–1101.[ISI][Medline]
10. Egger,M., Smith,G.D., Schneider,M. and Minder,C. (1997) Bias in meta-analysis detected by a simple graphical test. Br. Med. J., 315, 629–634.[Abstract/Free Full Text]
11. Brockmöller,J., Kerb,R., Drakoulis,N., Nitz,M. and Roots,I. (1993) Genotype and phenotype of glutathione S-transferase class µ isoenzymes µ and in lung cancer patients and controls. Cancer Res., 53, 1004–1011.[Abstract/Free Full Text]
12. Alexandrie,A.K., Sundberg,M.I., Seidegard,J., Tornling,G. and Rannug,A. (1994) Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types. Carcinogenesis, 15, 1785–1790.[Abstract/Free Full Text]
13. Kihara,M., Noda,K. and Kihara,M. (1995) Distribution of GSTM1 null genotype in relation to gender, age and smoking status in Japanese lung cancer patients. Pharmacogenetics, 5, S74–S79.
14. London,S.J., Daly,A.K., Cooper,J., Navidi,W.C., Carpenter,C.L. and Idle,J.R. (1995) Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California. J. Natl Cancer Inst., 87, 1246–1253.[Abstract/Free Full Text]
15. Deakin,M., Elder,J., Hendrickse,C. et al. (1996) Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis, 17, 881–884.[Abstract/Free Full Text]
16. Le Marchand,L., Sivaraman,L., Pierce,L., Seifried,A., Lum,A., Wilkens,L.R. and Lau,A.F. (1998) Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens. Cancer Res., 58, 4858–4863.[Abstract/Free Full Text]
17. Saarikoski,S.T., Voho,A., Reinikainen,M., Anttila,S., Karjalainen,A., Malaveille,C., Vainio,H., Husgafvel-Pursiainen,K. and Hirvonen,A. (1998) Combined effect of polymorphic GST genes on individual susceptibility to lung cancer. Int. J. Cancer, 77, 516–521.[ISI][Medline]
18. Salagovic,J., Kalina,I., Stubna,J., Habalova,V., Hrivnak,M., Valansky,L., Kohut,A. and Biros,E. (1998) Genetic polymorphism of glutathione S-transferases M1 and T1 as a risk factor in lung and bladder cancers. Neoplasma, 45, 312–317.[ISI][Medline]
19. Butkiewicz,D., Cole,K.J., Phillips,D.H., Harris,C.C. and Chorazy,M. (1999) GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms in lung cancer patients from an environmentally polluted region of Poland: correlation with lung DNA adduct levels. Eur. J. Cancer Prev., 8, 315–323.[ISI][Medline]
20. Persson,I., Johansson,I., Lou,Y.C., Yue,Q.Y., Duan,L.S., Bertilsson,L. and Ingelman-Sundberg,M. (1999) Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients. Int. J. Cancer, 81, 325–329.[ISI][Medline]
21. Stücker,I., de Waziers,I., Cenee,S., Bignon,J., Depierre,A., Milleron,B., Beaune,P. and Hemon,D. (1999) GSTM1, smoking and lung cancer: a case-control study. Int. J. Epidemiol., 28, 829–835.[Abstract/Free Full Text]
22. Ryberg,D., Skaug,V., Hewer,A., Phillips,D.H., Harries,L.W., Wolf,C.R., Ogreid,D., Ulvik,A., Vu,P. and Haugen,A. (1997) Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis, 18,1285–1289[Abstract/Free Full Text]
23. Jourenkova,N., Reinikanen,M., Bouchardy,C., Husgafvel-Pursiainen,K., Dayer,P., Benhamou,S. and Hirvonen,A. (1997) Effects of glutathione S-transferases GSTM1 and GSTT1 genotypes on lung cancer risk in smokers. Pharmacogenetics, 7, 515–518.[ISI][Medline]
24. To-Figueras,J., Gene,M., Gomez-Catalan,J., Galan,M.C., Fuentes,M., Ramon,J.M., Rodamilans,M., Huguet,E. and Corbella,J. (1997) Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms and lung cancer risk among Northwestern Mediterraneans. Carcinogenesis, 18, 1529–1533.[Abstract/Free Full Text]
25. Malats,N., Camus-Radon,A.M., Nyberg,F. et al. (2000) Lung cancer risk in non-smokers and GSTM1 and GSTT1 genetic polymorphisms. Cancer Epidemiol. Biomark. Prev., 9, 827–833.[Abstract/Free Full Text]
26. Garcia-Closas,M. and Lubin,J.H. (1999) Power and sample size calculations in case-control studies of gene–environment interactions: comments on different approaches. Am. J. Epidemiol., 149, 689–692.[Abstract/Free Full Text]
27. London,S.J., Yuan,J.M., Chung,F.L., Gao,Y.T., Coetzee,G.A., Ross,R.K. and Yu,M.C. (2000) Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung cancer risk: a prospective study of men in Shanghai, China. Lancet, 356, 724–729.[ISI][Medline]
28. Spitz,M.R., Duphorne,C.M., Detry,M.A., Pillow,P.C., Amos,C.I., Lei,L., de Andrade,M., Gu,X., Hong,W.K. and Wu,X. (2000) Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk. Cancer Epidemiol. Biomark. Prev., 9, 1017–1020.[Abstract/Free Full Text]
29. Hirvonen,A., Husgafvel-Pursiainen,K., Anttila,S. and Vainio,H. (1993) The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung. Carcinogenesis, 14, 1479–1481.[Abstract/Free Full Text]
30. Zhong,S., Howie,A.F., Ketterer,B., Taylor,J., Hayes,J.D., Becxkett,G.J., Wathen,C.G., Wolf,C.R. and Spurr,N.K. (1991) Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis, 12, 1533–1537.[Abstract/Free Full Text]
31. Cheng,T.J., Christiani,D.C., Wiencke,J.K., Wain,J.C., Xu,X. and Kelsey,K.T. (1995) Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls. Mutat. Res., 348, 75–82.[ISI][Medline]
32. Moreira,A., Martins,G., Monteiro,M.J. et al. (1996) Glutathione S-transferase mu polymorphism and susceptibility to lung cancer in the Portuguese population. Teratog. Carcinogen. Mutagen., 16, 269–274.
33. Garcia-Closas,M., Kelsey,K.T., Wiencke,J.K., Xu,X., Wain,J.C. and Christiani,D.C. (1997) A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility. Cancer Causes Control, 8, 544–553.[ISI][Medline]
34. Harrison,D.J., Cantlay,A.M., Rae,F., Lamb,D. and Smith,C.A. (1997) Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer. Hum. Exp. Toxicol., 16, 356–360.[ISI][Medline]
35. Woodson,K., Stewart,C., Barrett,M., Bhat,N.K., Virtamo,J., Taylor,P.R. and Albanes,D. (1999) Effect of vitamin intervention on the relationship between GSTM1, smoking, and lung cancer risk among male smokers. Cancer Epidemiol. Biomark. Prev., 8, 965–970.[Abstract/Free Full Text]
36. Belogubova,E.V., Togo,A.V., Kondratieva,T.V., Lemehov,V.G., Hanson,K.P. and Imyanitov,E.N. (2000) GSTM1 genotypes in elderly tumour-free smokers and non-smokers. Lung Cancer, 29, 189–195.[ISI][Medline]
37. Hou,S.M., Ryberg,D., Falt,S., Deverill,A., Tefre,T., Borresen,A.L., Haugen,A. and Lambert,B. (2000) GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients. Carcinogenesis, 21, 49–54.[Abstract/Free Full Text]
38. Nakachi,K., Imai,K., Hayashi,S.I. and Kawajiri,K. (1993) Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res., 53, 2994–2999.[Abstract/Free Full Text]
39. Katoh,T. (1994) The frequency of glutathione-S-transferase M1 (GSTM1) gene deletion in patients with lung and oral cancer. Jpn. J. Ind. Health, 36, 435–439.
40. Kawajiri,K., Watanabe,J., Eguchi,H. and Hayashi,S. (1995) Genetic polymorphisms of drug-metabolizing enzymes and lung cancer susceptibility. Pharmacogenetics, 5, S70–S73.
41. Ge,H., Lam,W.K., Lee,J., Wong,M.P., Yew,W.W. and Lung,M.L. (1996) Analysis of L-myc and GSTM1 genotypes in Chinese non-small cell lung carcinoma patients. Lung Cancer, 15, 355–366.[ISI][Medline]
42. Sun,G.F., Shimojo,N., Pi,J.B., Lee,S. and Kumagai,Y. (1997) Gene deficiency of glutathione S-transferase m isoform associated with susceptibility to lung cancer in a Chinese population. Cancer Lett., 113, 169–172.[ISI][Medline]
43. Hong,Y.S., Chang,J.H., Kwon,O.J., Ham,Y.A. and Choi,J.H. (1998) Polymorphism of the CYP1A1 and glutathione-S-transferase gene in Korean lung cancer patients. Exp. Mol. Med., 30, 192–198.[ISI][Medline]
44. Gao,Y. and Zhang,Q. (1999) Polymorphisms of the GSTM1 and CYP2D6 genes associated with susceptibility to lung cancer in Chinese. Mutat. Res., 444, 441–449.[ISI][Medline]
45. Wang,Y.C., Chen,C.Y., Wang,H.J., Chen,S.K., Chang,Y.Y. and Lin,P. (1999) Influence of polymorphism at p53, CYP1A1 and GSTM1 loci on p53 mutation and association of p53 mutation with prognosis in lung cancer. Chin. Med. J. (Tapei), 62, 395–403.
46. Lan,Q., He,X., Costa,D.J., Tian,L., Rothman,N., Hu,G. and Mumford,J.L. (2000) Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case-control study in Xuan Wei, China. Cancer Epidemiol. Biomark. Prev., 9, 605–608.[Abstract/Free Full Text]
47. Kelsey,K.T., Spitz,M.R., Zuo,Z.F. and Wiencke,J.K. (1997) Polymorphisms in the glutathione S-transferase class mu and theta genes interact and increase susceptibility to lung cancer in minority populations (Texas, United States). Cancer Causes Control, 8, 554–559.[ISI][Medline]
48. Ford,J.G., Li,Y., O’Sullivan,M.M., Demopoulos,R., Garte,S., Taioli,E. and Brandt-Rauf,P.W. (2000) Glutathione S-transferase M1 polymorphism and lung cancer risk in african-americans. Carcinogenesis, 21, 1971–1975.[Abstract/Free Full Text]
49. Harris,M.J., Coggan,M., Langton,L., Wilson,S.R. and Board,P.G. (1998) Polymorphism of the Pi class glutathione S-transferase in normal populations and cancer patients. Pharmacogenetics, 8, 27–31.[ISI][Medline]
50. Tang,D.L., Rundle,A., Warburton,D., Santella,R.M., Tsai,W.Y., Chiamprasert,S., Hsu,Y.Z. and Perera,F.P. (1998) Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers. Carcinogenesis, 19, 1949–1953.[Abstract/Free Full Text]
51. Dresler,C.M., Fratelli,C., Babb,J., Everley,L., Evans,A.A. and Clapper,M.L. (2000) Gender differences in genetic susceptibility for lung cancer. Lung Cancer, 30, 153–160.[ISI][Medline]
52. El-Zein,R., Zwischenberger,J.B., Wood,T.G., Abdel-Rahman,S.Z., Brekelbaum,C and Au,W.W. (1997) Combined genetic polymorphism and risk for development of lung cancer. Mutat. Res., 381, 189–200.[ISI][Medline]
53. Nyberg,F., Hou,S.M., Hemminki,K., Lambert,B. and Pershagen,G. (1998) Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls. Cancer Epidemiol. Biomark. Prev., 7, 875–883.[Abstract]
54. Nazar-Stewart,V., Motulsky,A.G., Eaton,D.L., White,E., Hornung,S.K., Leng,Z.T., Stapleton,P. and Weiss,N.S. (1993) The glutathione S-transferase µ polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res., 53, 2313–2318.[Abstract/Free Full Text]

Received November 19, 2001; revised April 29, 2002; accepted April 30, 2002.

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				P. Vineis, P. Brennan, F. Canzian, J. P. A. Ioannidis, G. Matullo, M. Ritchie, U. Stromberg, E. Taioli, and J. Thompson Expectations and challenges stemming from genome-wide association studies Mutagenesis, September 2, 2008; (2008) gen042v1. [Abstract] [Full Text] [PDF]

				E. Taioli Gene-environment interaction in tobacco-related cancers Carcinogenesis, August 1, 2008; 29(8): 1467 - 1474. [Abstract] [Full Text] [PDF]

				D. W. Bell, B. W. Brannigan, K. Matsuo, D. M. Finkelstein, R. Sordella, J. Settleman, T. Mitsudomi, and D. A. Haber Increased Prevalence of EGFR-Mutant Lung Cancer in Women and in East Asian Populations: Analysis of Estrogen-Related Polymorphisms Clin. Cancer Res., July 1, 2008; 14(13): 4079 - 4084. [Abstract] [Full Text] [PDF]

				S. C. Sanderson, S. E. Humphries, C. Hubbart, E. Hughes, M. J. Jarvis, and J. Wardle Psychological and Behavioural Impact of Genetic Testing Smokers for Lung Cancer Risk: A Phase II Exploratory Trial J Health Psychol, May 1, 2008; 13(4): 481 - 494. [Abstract] [PDF]

				K.-M. Lee, D. Kang, M. L. Clapper, M. Ingelman-Sundberg, M. Ono-Kihara, C. Kiyohara, S. Min, Q. Lan, L. Le Marchand, P. Lin, et al. CYP1A1, GSTM1, and GSTT1 Polymorphisms, Smoking, and Lung Cancer Risk in a Pooled Analysis among Asian Populations Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1120 - 1126. [Abstract] [Full Text] [PDF]

				S. S. Hecht, P. W. Villalta, and J.B. Hochalter Analysis of phenanthrene diol epoxide mercapturic acid detoxification products in human urine: relevance to molecular epidemiology studies of glutathione S-transferase polymorphisms Carcinogenesis, May 1, 2008; 29(5): 937 - 943. [Abstract] [Full Text] [PDF]

				C. Carlsten, G. S. Sagoo, A. J. Frodsham, W. Burke, and J. P. T. Higgins Glutathione S-Transferase M1 (GSTM1) Polymorphisms and Lung Cancer: A Literature-based Systematic HuGE Review and Meta-Analysis Am. J. Epidemiol., April 1, 2008; 167(7): 759 - 774. [Abstract] [Full Text] [PDF]

				P. Vineis, S. Anttila, S. Benhamou, M. Spinola, A. Hirvonen, C. Kiyohara, S. J. Garte, R. Puntoni, A. Rannug, R. C. Strange, et al. Evidence of gene gene interactions in lung carcinogenesis in a large pooled analysis Carcinogenesis, September 1, 2007; 28(9): 1902 - 1905. [Abstract] [Full Text] [PDF]

				A. J. Alberg, J. G. Ford, and J. M. Samet Epidemiology of Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition) Chest, September 1, 2007; 132(3_suppl): 29S - 55S. [Abstract] [Full Text] [PDF]

				P Vineis, F Veglia, S Garte, C Malaveille, G Matullo, A Dunning, M Peluso, L Airoldi, K Overvad, O Raaschou-Nielsen, et al. Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers Ann. Onc., July 1, 2007; 18(7): 1230 - 1242. [Abstract] [Full Text] [PDF]

				A. G. Schwartz, G. M. Prysak, C. H. Bock, and M. L. Cote The molecular epidemiology of lung cancer Carcinogenesis, March 1, 2007; 28(3): 507 - 518. [Abstract] [Full Text] [PDF]

				C. Carlsten and W. Burke Potential for Genetics to Promote Public Health: Genetics Research on Smoking Suggests Caution About Expectations JAMA, November 22, 2006; 296(20): 2480 - 2482. [Full Text] [PDF]

				S. S. Hecht, S. G. Carmella, A. Yoder, M. Chen, Z.-z. Li, C. Le, R. Dayton, J. Jensen, and D. K. Hatsukami Comparison of polymorphisms in genes involved in polycyclic aromatic hydrocarbon metabolism with urinary phenanthrene metabolite ratios in smokers. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1805 - 1811. [Abstract] [Full Text] [PDF]

				J. P A Ioannidis Commentary: Grading the credibility of molecular evidence for complex diseases Int. J. Epidemiol., June 1, 2006; 35(3): 572 - 578. [Full Text] [PDF]

				P. Yang, J. O. Ebbert, Z. Sun, and R. M. Weinshilboum Role of the Glutathione Metabolic Pathway in Lung Cancer Treatment and Prognosis: A Review J. Clin. Oncol., April 10, 2006; 24(11): 1761 - 1769. [Abstract] [Full Text] [PDF]

				J. E. Larsen, M. L. Colosimo, I. A. Yang, R. Bowman, P. V. Zimmerman, and K. M. Fong CYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung Carcinogenesis, March 1, 2006; 27(3): 525 - 532. [Abstract] [Full Text] [PDF]

				S. S. Hecht, M. Chen, A. Yoder, J. Jensen, D. Hatsukami, C. Le, and S. G. Carmella Longitudinal Study of Urinary Phenanthrene Metabolite Ratios: Effect of Smoking on the Diol Epoxide Pathway Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2969 - 2974. [Abstract] [Full Text] [PDF]

				C. M. McBride, I. M. Lipkus, D. Jolly, and P. Lyna Interest in Testing for Genetic Susceptibility to Lung Cancer among Black College Students "At Risk" of Becoming Cigarette Smokers Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2978 - 2981. [Abstract] [Full Text] [PDF]

				S. C. Sanderson and J. Wardle Will Genetic Testing for Complex Diseases Increase Motivation to Quit Smoking? Anticipated Reactions in a Survey of Smokers Health Educ Behav, October 1, 2005; 32(5): 640 - 653. [Abstract] [PDF]