Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
    • Progress and Priorities
    • Collections
      • COVID-19 & Cancer Resource Center
      • Disparities Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Informing Public Health Policy
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
    • Progress and Priorities
    • Collections
      • COVID-19 & Cancer Resource Center
      • Disparities Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Informing Public Health Policy
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Short Communications

Role of Polymorphisms in Codons 143 and 160 of the O6-Alkylguanine DNA Alkyltransferase Gene in Lung Cancer Risk

Tajinder B. Kaur, John M. Travaline, John P. Gaughan, John P. Richie Jr., Steven D. Stellman and Philip Lazarus
Tajinder B. Kaur
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John M. Travaline
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John P. Gaughan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John P. Richie Jr.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven D. Stellman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip Lazarus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published March 2000
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

O6-Alkylguanine DNA alkyltransferase (AGT) plays an important role in the repair of alkylating agent-induced DNA damage and protection from the carcinogenic effects of environmental agents. To examine the importance of the AGT codon 143 and codon 160 polymorphisms in risk for lung cancer and to assess the prevalence of these polymorphisms in different racial groups, we performed genotype analysis of lung cancer patients and matched controls. The prevalence of the AGT143Val allele in controls was 0.07 in Caucasians and 0.03 in African Americans. The AGT143Val allele was not detected in an unmatched Asian control cohort. The prevalence of the AGT160Arg variant allele was 0.01 in Caucasians, 0.02 in African Americans, and 0.03 in Asians. A marginally significant association was observed between the AGT codon 143 (isoleucine/valine) genotype and risk for lung cancer (odds ratio = 2.1; 95% confidence interval = 1.01–4.7). The prevalence of the AGT160Arg variant allele was similar in lung cancer cases versus matched controls. These results suggest that the AGT codon 143 polymorphism may play an important role in risk for lung cancer.

Introduction

The AGT3 DNA repair enzyme repairs O6-alkylguanine adducts induced in DNA by a variety of alkylating agents, including environmentally important N-nitroso compounds such as dimethylnitrosoamine and N-methyl-N′-nitro-N-nitrosoguanidine (1, 2, 3) . Cells lacking AGT are more sensitive to mutagenesis and demonstrate increased cytotoxicity when exposed to alkylating agents (2 , 4 , 5) . The repair of alkylguanine adducts may be directly correlated with cellular expression or activity of AGT (2 , 6, 7, 8, 9) . Increased AGT activity has been associated with decreased susceptibility to tumor induction by alkylating agents in transgenic mice (10 , 11) . DNA adducts induced by the tobacco-specific nitrosamine NNK are substrates for AGT (12 , 13) , and the defective repair of O6-alkylguanine by AGT in target cells and tissues may play a role in tumor induction in rodents treated with NNK (14) . These data are consistent with the fact that reduced capacity to repair O6-methylguanine adducts has been correlated with increased risk for lungcancer (7) .

The human AGT is a ubiquitous protein that irreversibly transfers an alkyl group from the O6 position of an adducted guanine to an internal cysteine residue at position 145 of the AGT protein. Mutations at the cysteine acceptor site or at positions in close proximity to this site can inactivate or significantly decrease AGT activity (3 , 15, 16, 17) . Two AA-altering polymorphisms in close proximity to the cysteine acceptor site (at codons 143 and 160) have recently been identified in the AGT gene (18 , 19) . Although functional studies have not yet been performed for the AGT143Val allele, this polymorphism is located almost adjacent to the alkyl acceptor Cys145 in the active site of the AGT enzyme. The polymorphism in codon 160 results in a Gly→Arg AA change in the AGT protein that codes for an AGT160Arg variant isoform, which exhibits significantly decreased activity in the repair of bulky alkylated DNA adducts as compared with the AGT160Gly wild-type isoform (20) . The overall goal of the present study was to assess the polymorphic prevalence of the codon 143 (Ile/Val) and codon 160 (Gly/Arg) genotypes in different racial groups and to examine the potential importance of these polymorphisms as potential risk factors for lung cancer.

Materials and Methods

Subjects.

This study was a retrospective case-control study using a 1:1 matched pair design for the purposes of minimizing differences due to age, sex, and race. Based on preliminary studies suggesting that the prevalence of the AGT codon 143 (Ile/Val) genotype is 21% (19) , power calculations using a 1:1 matching showed that 94 cases would be required to detect an OR of 2.5 for the AGT codon 143 (Ile/Val) genotype with 80% power at the 0.05% significance level. Due to the variation in the prevalence of the AGT codon 160 (Gly/Arg) genotype in different studies (18 , 19 , 21) , no power calculations were made for this polymorphism.

Cases (n = 139) were Caucasian or African American patients diagnosed with primary lung cancer and were identified between 1997 and 1999 at TUH (Philadelphia, PA). Diagnosis of lung cancer was provided by pathology confirmation (performed in the TUH Pathology Department), and all pathology-confirmed lung cancer patients who visited the Pulmonary Division at TUH were considered potentially eligible cases for our study. All of the cases entered into the study were recruited within 11 months after diagnosis, with 93% of all eligible cases recruited into the study. Of those eligible cases not recruited, three died before potential contact due to advanced disease. The histological distribution of lung cancer types was as follows: (a) adenocarcinoma (n = 38); (b) squamous cell carcinoma (n = 37); (c) small cell carcinoma (n = 31); (d) non-small cell carcinoma (n = 25); and (e) others (n = 8). Controls were individually matched to cases and were comprised of inpatients treated at TUH whose admitting diagnosis was unrelated to smoking. Exclusions for controls included cardiovascular disease, peripheral vascular disease, stroke and syncope, cirrhosis, emphysema, chronic bronchitis, chronic obstructive pulmonary disease, and other tobacco-related cancers (including bladder, esophageal, laryngeal, oral cavity, pancreatic, liver, and kidney cancer). The main diseases diagnosed in the matched control subjects were trauma and other ambulatory dysfunctions (34%), musculoskeletal (19%), gastrointestinal (11%), respiratory (10%), infectious (8%), and renal (6%). Eligible controls were, on average, recruited within 2 months of case recruitment by screening of TUH admission rosters for inpatients. The eligible control pool was restricted to subjects with the same age at diagnosis (± 5 years), race, and sex as cases. A detailed questionnaire containing questions on demographics and lifelong smoking habits was administered to all subjects. Tobacco use was categorized as described previously (22) . Smokers were classified as having smoked at least 1 cigarette/day for a minimum of 1 year (0.05 py). As a separate control group, we recruited 36 noncancerous, “healthy” TUH employees of Asian descent. These subjects were recruited to assess the prevalence of AGT polymorphic alleles in the Asian population and were not included in the lung cancer case-control study described above.

Genotype Analysis.

Buccal cell samples were collected from all subjects for the analysis of polymorphic genotypes, as approved by the TUH institutional review board. Informed consent was obtained from all subjects, with a consent rate of 98% for cases and 80% for controls who were asked to participate. Buccal cell samples were collected and processed, and DNA was isolated as described previously (22) . Because AGT codons 143 and 160 are both within exon 5 of the AGT gene, a single PCR amplification was performed for the screening of both codon 143 and codon 160 polymorphisms. PCRs were performed using 300 ng of sense (5′-TGACCCTTCCAGGTCCCCAT-3′) and antisense (5′-CACGTGTGTGTCGCTCAAAC-3′) primers homologous to exon 5 sequences of the AGT gene to generate a 262-bp fragment. A standard PCR was performed as described previously (22) with a primer annealing step of 58°C for 45 s. A separate PCR amplification was also performed for a DNA specimen (chosen at random) using a codon 143 Val-encoding sense primer (5′-TGACCCTTCCAGGTCCCCATCCTCGTCC-3′) that contains a guanine (underlined nucleotide in the primer sequence) at the polymorphic nucleotide site of AGT codon 143. This PCR amplimer was used as a positive control for the homozygous codon 143 (Val/Val) genotype during single-nucleotide primer extension analysis. The AGT codon 160 Gly/Arg polymorphism was screened by PCR-RFLP analysis by digestion with BspEI (New England Biolabs, Beverly, MA). The AGT codon 143 Ile/Val polymorphism was screened using 50–100 ng of PCR product isolated after electrophoresis in low-melting point agarose using a modified single-nucleotide primer extension procedure similar to that described previously (23) . Separate reactions were performed using either [α-32P]dATP or[α -32P]dGTP (10 mCi/ml and 3000 Ci/mmol for both radiolabeled nucleotides; New England Nuclear, Boston, MA) for each low-melting point agarose-purified PCR-amplified DNA sample. Samples were subjected to one incubation cycle consisting of 95°C for 3 min, 60°C for 30 s, and 72°C for 40 s before sample processing and electrophoresis. All genotyping analysis was repeated for at least 20% of the specimens, and selected PCR-amplified DNA samples (n = 2 for both the wild-type and heterozygous genotypes for each polymorphism) were examined by dideoxy DNA sequencing to confirm AGT genotyping results.

Statistics.

The risk of lung cancer in relation to AGT genotype and smoking was estimated using conditional logistic regression appropriate for a 1:1 matched pair design to calculate ORs and 95% CIs, adjusting for age, sex, race, and py. The potential association between AGT polymorphisms and lung cancer risk was analyzed for informative case-control pairs using the Pearson’s χ2 test analysis. To analyze the potential association between AGT genotype and lung cancer risk after stratification into smoking categories, multiple logistic regression analysis was performed after adjusting for age, sex, race, and py. Student’s t test (two-tailed) was used for comparing continuous variables such as smoking between cases and controls. All Ps presented are two-sided. The statistical computer software SAS/STAT (version 6.12, fourth edition, Vol. 2; SAS Institute, Inc., Cary, NC) was used to perform all statistical analysis.

Results and Discussion

A total of 56 Caucasian and 83 African-American lung cancer cases and an equal number of individually matched controls were entered into the study. The average age was identical for cases and controls (63 years for African Americans and 66 years for Caucasians), and the male:female ratio was virtually the same for African Americans (55% male) and Caucasians (57% male). For Caucasians, 89% of cases and 71% of controls were ever-smokers (i.e., <0.05 py), whereas 99% of cases and 85% of controls were ever-smokers in the African-American group. Cigarette consumption was significantly higher in cases (48 py for African Americans and 52 py for Caucasians) as compared to controls (30 py for African Americans and 32 py for Caucasians) for both racial groups (P < 0.005 for Caucasians and P < 0.002 for African Americans). The mean age of the unmatched, noncancerous Asian cohort was 37 years, and 58% of these subjects were male. This Asian cohort (n = 36) was 69% Chinese, 14% Korean, 11% Vietnamese, 3% Filipino, and 3% Japanese.

The AGT160Arg allelic prevalence in controls was 0.009 for Caucasians and 0.019 for African Americans (Table 1)⇓ . The AGT160Arg allele was observed in 6% of the Asian cohort (allelic prevalence = 0.029). Both of the Asian subjects with a detectable AGT160Arg allele were of Chinese descent. The prevalence of the AGT143Val allele in controls was 0.073 for Caucasians and 0.031 for African Americans. The AGT143Val allele was not detected in the Asian control group.

View this table:
  • View inline
  • View popup
Table 1

Prevalence of AGT143Val and AGT160Arg alleles in controls

A marginally significant association was observed between the AGT codon 143 (Ile/Val) genotype and increased risk for lung cancer, regardless of whether this analysis was performed by analyzing crude genotyping data (χ2 = 3.98; P = 0.047) or by conditional logistic regression analysis (OR = 2.1, 95% CI = 1.01–4.7; Table 2⇓ ). Similar increases in risk were observed for African Americans (OR = 2.3, 95% CI = 0.73–8.3) and Caucasians (OR = 2.0, 95% CI = 0.78–5.7). A similar prevalence of the AGT160Arg allele was observed for both lung cancer cases and controls for African Americans and Caucasians.

View this table:
  • View inline
  • View popup
Table 2

Prevalence of AGT codon 143 and 160 polymorphic genotypes in lung cancer cases and matched controls

To examine the effects of smoking, the AGT143Val allele and lung cancer risk were examined separately in smokers. Smokers [never-smokers (n = 7) were excluded from this analysis] were categorized into two groups based on lifetime smoking history divided at the median py for all subjects (32 py). Similar risk was observed in both the light-smoking (≤32 py; OR = 1.6, 95% CI = 0.33–7.3) and heavy-smoking (>32 py; OR = 1.7, 95% CI = 0.61–4.7) groups. A test for interaction between genotype and smoking was not significant in our conditional logistic regression model for lung cancer risk.

Many studies have examined the role of genetic polymorphisms in susceptibility to environmental carcinogens. The majority of these studies have focused on polymorphisms present in genes coding for enzymes involved in carcinogen metabolism. Few studies have reported on DNA repair as a mechanism for differential cancer susceptibility. Codon 143 in the AGT gene encodes an AA located within the active site of the AGT protein, two AAs upstream of the alkyl acceptor Cys145. The Ile143 is conserved among all known mammalian AGTs, and although an Ile→Val AA change similar to that observed at AGT codon 143 is conservative in nature, previous studies have shown that the polymorphic Ile→Val AA change at codon 105 of the glutathione S-transferase P1 gene is associated with decreased catalytic activity of the variant glutathione S-transferase π protein (24) . In addition, although not in the active site of the AGT protein, the genetically linked codon 178 Lys→Arg AA change within the AGT143Val variant may alter the function of this protein. Function-activity relationships of the AGT143Val variant must be established for both the codon 143 and codon 178 polymorphic sites to better assess their potential importance in relation to lung cancer risk.

The association between the AGT143Val variant and lung cancer risk observed in this study suggests that decreased activity in the repair of adducts generated by tobacco smoke carcinogens confers increased risk for lung cancer for subjects with this variant allele. Although no difference in attributable risk was observed in subjects at different smoking doses, the AGT143Val variant may interact with tobacco smoke carcinogens to confer risk in all smokers. It is not known whether the AGT143Val exhibits altered activity toward the repair of specific types of adducts similar to that observed for the AGT160Arg variant (20) . If the AGT143Val variant exhibits altered repair activity against methylated adducts, such studies could potentially link AGT polymorphisms and lung cancer susceptibility with adducts induced by alkylating tobacco carcinogens such as NNK (14) . Because only seven cases in our study were never-smokers, a larger study will be required to examine potential associations in smokers versus never-smokers.

In a recent study, the AGT143Val allele was detected in 21% of a small cohort of noncancerous Caucasian controls but was not detected in 60 noncancerous Chinese controls (19) . A difference in AGT143Val allelic prevalences between racial groups was also observed in the present study. The difference in AGT143 genotype prevalence between these two studies is likely due to the low number of Caucasian subjects (n = 28) screened in the earlier study (19) . By contrast, variability in the prevalence of the AGT160Arg allele has been observed between studies of different cohorts of the same race. Imai et al. (18) described the presence of this allele in 3 of 28 healthy Japanese controls. However, this allele was not detected in two studies examining allelic prevalence in Caucasians (19 , 21) , African Americans (21) , and Asians [including Chinese (19) and a small cohort of Japanese (21)] . In the present study, we confirm the existence of the AGT160Arg allele in humans; however, it appears to be present at a low prevalence (i.e., ≤0.03) in multiple racial groups. This is consistent with studies demonstrating the lack of a O6-benzylguanine-resistant AGT phenotype in Caucasians and Japanese (25) . Although the data from the present study suggest that the AGT160Arg allele is not associated with a high degree of attributable risk for lung cancer, the low prevalence of this allele necessitates that a much larger study be performed to obtain sufficient power for an efficient risk assessment analysis.

Acknowledgments

We thank Jong Park for critical comments and review of the manuscript, Mark Pietras and Megan Grossman for excellent technical assistance, and Donald Pollard and Michelle Hayes for assistance in subject identification and recruitment.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • ↵1 Supported in part by NIH Grants CA59917 (to P. L.), DE12206 (to P. L.), and CA68384 (to S. D. S.).

  • ↵2 To whom requests for reprints should be addressed: H. Lee Moffitt Cancer Center, MRC-3E, 12902 Magnolia Drive, Tampa, FL 33612. Fax: (813) 903-6817; E-mail: plazarus{at}moffitt.usf.edu

  • ↵3 The abbreviations used are: AGT, O6-alkylguanine DNA alkyltransferase; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; AA, amino acid; TUH, Temple University Hospital; py, pack-years; OR, odds ratio; CI, confidence interval.;lmm;jmr(v)>

  • Received June 21, 1999.
  • Revision received December 21, 1999.
  • Accepted January 17, 2000.

References

  1. ↵
    Montesano R., Becker R., Hall J., Likhachev A., Lu S. H., Umbenhauer D., Wild C. P. Repair of DNA alkylation adducts in mammalian cells. Biochimie (Paris), 67: 919-928, 1985.
    OpenUrlPubMed
  2. ↵
    Pegg A. E. Mammalian O6-alkylguanine DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res., 50: 6119-6129, 1990.
    OpenUrlFREE Full Text
  3. ↵
    Edara S., Kanugula S., Pegg A. E. Expression of the inactive C145A mutant human O6-alkylguanine DNA alkyltransferase in E. coli increases cell killing and mutations by N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis (Lond.), 20: 103-108, 1999.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Brent T. P. Isolation and purification of O6-alkylguanine DNA alkyltransferase from human leukemic cells. Prevention of chloroethylnitrosourea-induced cross-links by purified enzyme.. Pharmacol. Ther., 31: 121-140, 1985.
    OpenUrlCrossRefPubMed
  5. ↵
    Ludlum D. B. DNA alkylation by the haloethylnitrosoureas: nature of modifications produced and their enzymatic repair or removal. Mutat. Res., 233: 117-126, 1990.
    OpenUrlCrossRefPubMed
  6. ↵
    Sagher D., Karrison T., Schwartz J. L., Larson R., Meier P., Strauss B. Low O6-alkylguanine DNA alkyltransferase activity in peripheral blood lymphocytes of patients with therapy related acute nonlymphocytic leukemia. Cancer Res., 48: 3084-3089, 1988.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    Rudiger H. W., Schwartz U., Serrand E., Stief M., Krause T., Nowak D., Doerjer G., Lehnert G. R. Reduced O6-methylguanine repair in fibroblast cultures from patients with lung cancer. Cancer Res., 49: 5623-5626, 1989.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Aquilina G., Biondo R., Dogliotti E., Meuth M., Bignami M. Expression of the endogenous O6-methylguanine DNA methyltransferase protects Chinese hamster ovary cells from spontaneous G: C to A:T transitions. Cancer Res., 52: 6465-6471, 1992.
    OpenUrl
  9. ↵
    Pegg A. E., Swenn K., Dolan M. E., Moschel R. G. Increased killing of prostate breast, colon and lung tumor cells by the combination of inactivators of O6-alkylguanine DNA alkyltransferase and N,N-bis(2-chloroethyl)-N-nitrosourea. Biochem. Pharmacol., 50: 1141-1148, 1995.
    OpenUrlCrossRefPubMed
  10. ↵
    Dumenco L. L., Allay E., Norton K., Gerson S. L. The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine DNA alkyltransferase. Science (Washington DC), 259: 219-222, 1993.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    Nakatsura Y., Matsukuma S., Nemoto N., Sugano H., Sekiguchi M., Ishikawa T. O6-Methylguanine DNA methyltransferase protects against nitrosamine-induced hepatocarcinogenesis. Proc. Natl. Acad. Sci. USA, 90: 6468-6472, 1993.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    Belinsky S. A., Dolan M. E., White C. W., Maronpot R. R., Pegg A. E., Anderson M. E. Cell-specific differences in O6-alkylguanine DNA alkyltransferase activity and removal of O6-methylguanine in rat pulmonary cells. Carcinogenesis (Lond.), 9: 2053-2058, 1988.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    Wang L., Spratt T. E., Liu X. K., Hecht S. S., Pegg A. E., Peterson L. A. Pyridyloxobutyl adduct O6-[4-oxo-4-(3-pyridyl)butyl]guanine is present in 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone-treated DNA and is a source for O6-alkylguanine DNA alkyltransferase. Chem. Res. Toxicol., 10: 562-567, 1997.
    OpenUrlCrossRefPubMed
  14. ↵
    Peterson L. A., Hecht S. S. O6-Methylguanine is a critical determinant of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res., 51: 5557-5564, 1991.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    Crone T. M., Pegg A. E. A single amino acid change in human O6-alkylguanine DNA alkyltransferase decreasing sensitivity to inactivation by O6-benzylguanine. Cancer Res., 53: 4750-4753, 1993.
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Crone T. M., Goodtzova K., Edara S., Pegg A. E. Mutations in O6-alkylguanine DNA alkyltransferase imparting resistance to O6-benzylguanine. Cancer Res., 54: 6221-6227, 1994.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    Edara S., Goodtzova K., Pegg A. E. The role of tyrosine in O6-alkylguanine DNA alkyltransferase activity. Carcinogenesis (Lond.), 16: 1637-1642, 1995.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Imai T., Oda H., Nakatsuru Y., Ishikawa T. A polymorphism at codon 160 of human O6-methylguanine DNA methyltransferase gene in young patients with adult type cancers and functional assay. Carcinogenesis (Lond.), 16: 2441-2445, 1995.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    Deng C. J., Xie D. W., Zhao Y. J., Wang L. D., Hong J. Y. Identification of a novel genetic polymorphism of human O6-alkylguanine DNA alkyltransferase. Pharmacogenetics, 9: 81-87, 1999.
    OpenUrlPubMed
  20. ↵
    Edara S., Kanugula S., Goodtzova K., Pegg A. E. Resistance of the human O6-alkylguanine DNA alkyltransferase containing arginine at codon 160 to inactivation by O6-benzylguanine. Cancer Res., 56: 5571-5575, 1996.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    Wu M. H., Lohrbach K. E., Olopade O. I., Kokkinakis D. M., Freidman H. S., Dolan M. E. Lack of evidence for a polymorphism at codon 160 of human O6-alkylguanine-DNA alkyltransferase gene in normal tissue and cancer. Clin Cancer Res., 5: 209-213, 1999.
    OpenUrlAbstract/FREE Full Text
  22. ↵
    Park J., Muscat J. E., Ren Q., Schantz S. P., Harwick R. D., Stern J. C., Pike V., Richie J. P., Jr., Lazarus P. CYP1A1 and GSTM1 polymorphisms and oral cancer risk. Cancer Epidemiol. Biomark. Prev., 6: 791-797, 1997.
    OpenUrlAbstract/FREE Full Text
  23. ↵
    Kuppuswamy M. N., Hoffmann J. W., Kasper C. K., Spitzer S. G., Groce S. L., Bajaj S. P. Single nucleotide primer extension to detect genetic diseases: experimental application to hemophilia B (factor IX) and cystic fibrosis genes. Proc. Natl. Acad. Sci. USA, 88: 1143-1147, 1991.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    Ali-Osman F., Akande O., Antoun G., Mao X. J. Molecular cloning, characterization, and expression in Escherichia coli of full length cDNAs of three human glutathione S-transferase π gene variants. J. Biol. Chem., 272: 10004-10012, 1997.
    OpenUrlAbstract/FREE Full Text
  25. ↵
    Gerson S. L., Schupp J., Liu L., Pegg A. E., Srinivasen S. Leukocyte O6-alkylguanine-DNA alkyltransferase from human donors is uniformly sensitive to O6-benzylguanine. Clin. Cancer Res., 5: 521-524, 1999.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
March 2000
Volume 9, Issue 3
  • Table of Contents

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Epidemiology, Biomarkers & Prevention article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Role of Polymorphisms in Codons 143 and 160 of the O6-Alkylguanine DNA Alkyltransferase Gene in Lung Cancer Risk
(Your Name) has forwarded a page to you from Cancer Epidemiology, Biomarkers & Prevention
(Your Name) thought you would be interested in this article in Cancer Epidemiology, Biomarkers & Prevention.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Role of Polymorphisms in Codons 143 and 160 of the O6-Alkylguanine DNA Alkyltransferase Gene in Lung Cancer Risk
Tajinder B. Kaur, John M. Travaline, John P. Gaughan, John P. Richie Jr., Steven D. Stellman and Philip Lazarus
Cancer Epidemiol Biomarkers Prev March 1 2000 (9) (3) 339-342;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Role of Polymorphisms in Codons 143 and 160 of the O6-Alkylguanine DNA Alkyltransferase Gene in Lung Cancer Risk
Tajinder B. Kaur, John M. Travaline, John P. Gaughan, John P. Richie Jr., Steven D. Stellman and Philip Lazarus
Cancer Epidemiol Biomarkers Prev March 1 2000 (9) (3) 339-342;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results and Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Cancer Predisposition Gene Mutations and Pancreatic Cancer
  • Statin Use and Breast Cancer Risk
  • Tamoxifen and Longitudinal Mammographic Density Change
Show more Short Communications
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Epidemiology, Biomarkers & Prevention

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Epidemiology, Biomarkers & Prevention
eISSN: 1538-7755
ISSN: 1055-9965

Advertisement