CEBP Prevention Award Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ntais, C.
Right arrow Articles by Ioannidis, J. P.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ntais, C.
Right arrow Articles by Ioannidis, J. P.A.
Cancer Epidemiology Biomarkers & Prevention Vol. 14, 176-181, January 2005
© 2005 American Association for Cancer Research

Association of GSTM1, GSTT1, and GSTP1 Gene Polymorphisms with the Risk of Prostate Cancer: A Meta-analysis

Christos Ntais1, Anastasia Polycarpou1 and John P.A. Ioannidis1,2,3

1 Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine; 2 Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece; and 3 Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts

Requests for reprints: John P.A. Ioannidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. Phone: 265-109-7807; Fax: 265-109-7867. E-mail: jioannid{at}cc.uoi.gr.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The glutathione S-transferase (GST) gene superfamily encodes for enzymes involved in conjugation of electrophilic compounds to glutathione. Several polymorphisms in the GST genes have been implicated as risk factors for prostate cancer. We did a meta-analysis of 11 studies with GSTM1 genotyping (2,063 prostate cancer cases and 2,625 controls), 10 studies with GSTT1 genotyping (1,965 cases and 2,554 controls), and 12 studies with GSTP1 genotyping (2,528 cases and 3,076 controls). The random effects odds ratio was 1.08 [95% confidence interval (95% CI), 0.93-1.25, no significant between-study heterogeneity] for the GSTM1 null versus nondeleted genotype and 0.90 (95% CI, 0.73-1.12; P = 0.03 for heterogeneity) for the GSTT1 null versus nondeleted genotype. Overall, the random effects odds ratio was 1.05 (95% CI, 0.90-1.21; P < 0.01 for heterogeneity) for the GSTP1-Val versus GSTP1-Ile allele. For all three polymorphisms, there was a trend for the presence of an association in the earliest published studies, but this did not seem to be validated in subsequent research. For GSTT1, larger studies gave different results than smaller ones. The meta-analysis shows that these three polymorphisms are unlikely to be major determinants of susceptibility to prostate cancer on a wide population basis.

Key Words: GST • prostate cancer • polymorphism • glutathione S-transferase • meta-analysis


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The glutathione S-transferase (GST) gene superfamily consists of four gene classes (A, M, T, and P) encoding for enzymes which catalyze the conjugation of electrophilic compounds to glutathione (1). These enzymes are also believed to play a crucial role in the protection of DNA from oxidative damage (2). GSTM1 and GSTT1 have different substrate specificities in detoxification of carcinogenic polycyclic aromatic hydrocarbons (1). Moreover, GSTT1 may also catalyze the activation of certain xenobiotics to genotoxic metabolites, such as dichloromethane and other halogenated alkanes (3, 4); thus, the net effect (protection or susceptibility) in relationship to carcinogenesis, if any, is difficult to predict. GSTM1 activity is absent in ~40% to 60% of the Caucasian population as a result of the inheritance of two null alleles (5). Similarly, GSTT1 activity is absent (homozygous gene deletion) in ~20% to 30% of Caucasians (5). GSTP1 is a major enzyme involved in the inactivation of cigarette smoke carcinogens, such as benzo [a]pyrene diol epoxide, and other toxic constituents, such as acrolein (1). GSTP1 expression has been studied in preneoplastic and neoplastic prostate lesions (6-9). An A313G transition in exon 5 of the GSTP1 gene, which replaces isoleucine at codon 105 with valine (I105V) within the active site of the enzyme, has been identified (10). This substitution is associated with reduced enzymatic activity for certain substrates and altered thermostability (11, 12).

Molecular epidemiologic studies have presented inconclusive results concerning a potential role of the GSTM1 (13-23), GSTT1 (15-24), and GSTP1 (10, 15-21, 25-28) polymorphisms in prostate cancer susceptibility. Single studies may have been underpowered to detect modest effects. Given the amount of accumulated data, a quantitative synthesis of the evidence and analysis of the between-study heterogeneity was deemed important to perform.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Identification and Eligibility of Relevant Studies and Data Extraction
We considered all studies that examined the association of the GSTM1, GSTT1, and GSTP1 polymorphisms with prostate cancer. Sources included MEDLINE, EMBASE, and the HuGENet database (last search update 4/2004). The search strategy was based on combinations of "prostate cancer," "glutathione S-transferase," "GST," "polymorphism," "allele," and "genetics." References of retrieved articles were also screened.

The meta-analysis was designed on the same principles as previous meta-analyses of candidate genetic risk factors for prostate cancer done by our team (29-31). Methodology is given in detail in previous publications (29-31). In brief, studies of unrelated prostate cancer cases and prostate cancer-free controls [with or without benign prostatic hyperplasia (BPH)] were eligible. Cases with prostate cancer were eligible regardless of whether they had a first-degree relative with prostate cancer or not. Among overlapping reports, we retained the one with largest sample size.

Meta-analysis
The analysis for GSTM1 and GSTT1 polymorphisms compared cases against controls for the contrast of the null (homozygous deletion of the gene) versus the nondeleted genotype (heterozygous or homozygous presence of the gene), as originally proposed (15). The analysis for the GSTP1 polymorphism was based on the contrast of alleles.

The odds ratio (OR) was used as the metric of choice. For each genetic contrast, we estimated the between-study heterogeneity across all eligible comparisons using the {chi}2-based Q statistic (considered significant for P < 0.10; ref. 32). Data were combined using both fixed effects (Mantel-Haenszel) and random effects (DerSimonian and Laird) models (32). Random effects incorporate an estimate of the between-study variance and provide wider 95% confidence intervals (95% CI), when the results of the constituent studies differ among themselves. Random effects are reported unless stated otherwise. Subgroup analyses estimated race-specific ORs.

Cumulative meta-analysis (33) and recursive cumulative meta-analysis (34, 35) evaluated whether the summary ORs changed over time as data accumulated (36). Inverted funnel plots and the Begg-Mazumdar diagnostic (nonparametric {tau} correlation coefficient; ref. 37) evaluated whether the magnitude of the observed association was related to each study's variance (38). Finally, we evaluated whether the summary results were different when the analyses were limited to studies that confirmed histologically all prostate cancer cases and specifically screened all controls to rule out prostate cancer.

Analyses were conducted in SPSS 11.0 (SPSS, Inc., Chicago, IL), StatXact (Cytel Inc., Boston, MA), and Meta-Analyst (Joseph Lau, Boston, MA). All Ps are two tailed.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Eligible Studies
Excluding overlapping data, we identified 17 eligible reports (10, 13-28) with 11, 10, and 12 studies on GSTM1 (13-23), GSTT1 (15-24), and GSTP1 (10, 15-21, 25-28), respectively. There was a considerable diversity of ethnic groups. Twelve reports (13-20, 23-26) selected prostate cancer patients based on a histologic diagnosis from biopsy or prostatectomy, whereas the other five (10, 21, 22, 27, 28) did not clarify the exact diagnostic criteria. Three reports (17, 19, 27) mentioned positive family history of prostate cancer in 12.4%, 13.7%, and 100% of patients, respectively, whereas the remaining did not comment on family history. Controls did not have a clinical diagnosis of prostate cancer at study entry, but the amount of additional screening to exclude prostate cancer differed substantially across studies (Table 1).


View this table:
[in this window]
[in a new window]

  		Table 1. Characteristics of studies included in the meta-analyses

 
With four exceptions (14-16, 25) where the mean age of controls and cases differed by ≥3 years, the reported mean or median age of cases and controls was very similar (difference, ≤2 years) and specific matching for age was described in six studies (20-23, 27, 28). One study also matched for smoking status (28). Only three reports (17, 20, 28) mentioned specifically blinding of the personnel who did the genotyping. All studies used PCR. The distribution of genotypes in control groups was consistent with Hardy-Weinberg equilibrium for the GSTP1 polymorphism in all studies.

Meta-analyses Databases
GSTM1. The eligible studies included 2,098 patients with prostate cancer and 2,728 controls of whom 2,063 and 2,625, respectively, had genotype data. The null genotype was similarly common among controls of Caucasian descent (48%; 95% CI, 45-51) and Asian descent (45%; 95% CI, 39-51). In controls of Caucasian descent, prevalence was relatively similar in most countries (54% in Denmark, 53% in the United States, 50% in the United Kingdom and Portugal, 49% in Austria, and 45% in Germany), but it was surprisingly low in a Chilean study (23%).

GSTT1. The eligible studies included 1,996 patients with prostate cancer and 2,592 controls of whom 1,965 and 2,554, respectively, had genotype data. The overall prevalence of the null genotype was 19% (95% CI, 17-21) and 49% (95% CI, 43-55) in control subjects of Caucasian and Asian descent, respectively. The prevalence rates of the null genotype across the controls of Caucasian descent were 24% in Portugal and United Kingdom, 20% in Austria, 15% in Denmark and the United States, and 13% in Germany.

GSTP1. The eligible studies included 2,574 patients with prostate cancer and 3,122 controls of whom 2,528 and 3,076, respectively, had genotype data. The prevalence of the Val allele was 32% (95% CI, 31-33) and 14% (95% CI, 9-19) in control subjects of Caucasian and Asian descent, respectively. The prevalence rates of the Val allele across the control subjects of Caucasian descent were 38% in Austria; 33% in Portugal; 33% in Sweden, Denmark, and the United States; 30% in the United Kingdom; and 27% in Germany. Overall, the prevalence of Val/Val homozygosity was 11% and 0% in control subjects of Caucasian and Asian descent, respectively. The respective prevalence rates of Ile/Val heterozygosity were 43% and 28%.

Quantitative Synthesis
GSTM1.There was no evidence that the null genotype modified the risk of prostate cancer (Fig. 1A). The summary OR was 1.08 (95% CI, 0.93-1.25, P = 0.34), without statistically significant between-study heterogeneity. No association was observed in subjects of Caucasian (OR, 1.11; P = 0.39, P = 0.04 for between-study heterogeneity) and Asian descent (OR, 1.11, P = 0.61, no significant between-study heterogeneity).



View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. A. Effect of the GSTM1 null versus nondeleted genotype on the risk of prostate cancer. Each comparison is presented by the name of the first author and the year of publication. As, subjects of Asian descent. Point estimate of the OR and the accompanying 95% CI for each comparison. Summary random effects estimate for the comparison along with the respective 95% CI. Values >1, an increased risk for prostate cancer with the null genotype. B. Effect of the GSTT1 null versus nondeleted genotype on the risk of prostate cancer. Values >1, an increased risk for prostate cancer with the null genotype. Otherwise, figure set up as per Fig. 1A. C. Effect of the GSTP1-Val versus GSTP1-Ile allele on the risk of prostate cancer. Values >1, an increased risk for prostate cancer with the Val allele. Otherwise, figure set up as per Fig. 1A.

 
GSTT1. The contrast of genotypes did not suggest any strong genetic effect (Fig. 1B). The summary OR was 0.90 (95% CI, 0.73-1.12; P = 0.34) and there was statistically significant between-study heterogeneity (P = 0.03 for heterogeneity). We also found no evidence of an association in subjects of Caucasian descent (OR, 1.04; P = 0.78, no significant between-study heterogeneity) and Asian descent (OR, 0.91; P = 0.80, P = 0.05 for between-study heterogeneity).

GSTP1. There was no evidence that the Val allele modified the risk of prostate cancer (Fig. 1C). The summary OR was 1.05 (95% CI, 0.90-1.21; P = 0.54) and there was highly significant heterogeneity among the 11 study comparisons (P < 0.01 for heterogeneity). No association was observed in subjects of Caucasian descent (OR, 1.02; P = 0.81, P < 0.01 for between-study heterogeneity) and there was only one study with subjects of Asian descent (OR, 1.25; P = 0.44).

Bias Diagnostics
GSTM1. The magnitude of the summary OR had not been stable over time and it had changed considerably per year with an apparent continuous dissipation of the postulated effect (by random effects, summary OR for null versus nondeleted genotype was 1.32 at the end of 1998, 1.30 in 1999, 1.15 in 2000, 1.13 in 2001, 1.07 in 2003, and 1.08 in 2004). The effect size was not related to study variance (P = 0.39). Analyses limited to studies with rigorous selection of cases and controls yielded similar results [9 comparisons (3,625 subjects); OR, 1.14; 95% CI, 1.00-1.30, no significant between-study heterogeneity].

GSTT1. The magnitude of the summary OR continuously diminished over time (by random effects, summary OR for null versus nondeleted genotype was 1.30 at the end of 1999, 1.15 in 2000, 0.94 in 2001, 0.91 in 2003, and 0.90 in 2004). Moreover, there was evidence that larger studies showed different results than smaller studies (P = 0.09 for the tau correlation between the natural logarithm of the OR and the study variance). Analyses limited to studies with rigorous selection of cases and controls excluded any effect [8 comparisons (3,403 subjects); OR, 0.98; 95% CI, 0.77-1.25; P = 0.05 for between-study heterogeneity].

GSTP1. The magnitude of the summary OR had not been stable over time and it had changed considerably after the first year (by random effects, summary OR for Val versus Ile was 1.56 at the end of 1997, 1.11 in 1999, 0.99 in 2000, 1.00 in 2001, 1.02 in 2002, and 1.05 in 2003). The effect size was not related to study variance (P = 0.31). Analyses limited to studies with rigorous selection of cases and controls yielded similar results [8 comparisons (6,726 alleles); OR, 1.04; 95% CI, 0.86-1.25; P < 0.01 for heterogeneity].


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The current evidence does not show any increased risk for prostate cancer conferred by these three common GST polymorphisms and the 95% CIs are narrow enough to exclude a large genetic effect. Whereas a trend for potential genetic effects was suggested in early data for all three polymorphisms, this was not validated with subsequent research. Postulated genetic associations for prostate cancer need to be carefully validated across several studies, because early and small genetic association studies may come up with spurious findings (36, 38-40).

The biochemical evidence for a putative relationship of these GST polymorphisms with prostate cancer is also equivocal. These enzymes may regulate pathways that prevent damage from several carcinogens (1-4). However, it is unlikely that specific environmental carcinogens whose effect might also be modifiable by GST genotype have a high attributable fraction for prostate cancer. For GSTT1 in particular, protective and susceptibility effects to cancer may counterbalance each other. In addition to metabolism of chemical carcinogens, GST enzymes metabolize steroid hormones, compounds found in the diet, and other agents potentially involved in prostate carcinogenesis. Furthermore, GST enzymes are involved in the intracellular transport of steroid hormones (41) and the isomerization of androst-5-ene-3,17-dione to androst-4-ene-3,17-dione, the immediate precursor of testosterone (1). However, the exact role of steroid hormones in the pathogenesis of prostate cancer has been a contentious issue (42, 43). Polymorphisms in genes coding for enzymes of the androgen biosynthesis and metabolism pathway have also been postulated as prostate cancer determinants (44, 45), but meta-analyses have yielded mostly negative results (29, 30).

The GST polymorphisms have also been studied extensively in terms of susceptibility for other malignancies. Previous meta-analyses on these polymorphisms yielded negative results for breast (46) and colon cancer (47), whereas others have suggested the possible presence of modest associations for head and neck (48), lung (49), and bladder cancer (50). Nevertheless, even in the latter cases, the summary ORs have been small (in the range of 1.17-1.44).

Some analytic issues should also be considered. First, some nondifferential misclassification bias is possible. Most studies could not exclude latent prostate cancer cases in the control group. Furthermore, control groups included a large, often unknown proportion of subjects with BPH. BPH may be also affected by these same polymorphisms, but susceptibility to prostate enlargement is a different issue than susceptibility to cancer. We could not address whether these GST polymorphisms may have an effect on the clinical behavior of prostate cancer or other clinicopathologic attributes. The meta-analysis cannot exclude the possibility that other polymorphisms in GST genes may still be useful to pursue. Moreover, we could not address gene-gene and gene-environmental interactions. The latter may be important for genes that code proteins with detoxifying function, but would require detailed information on exposures to various potential carcinogens and individual-level data (51) and would be most meaningful only for common exposures that are found to be strong risk factors for the disease.


   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.

Received 5/11/04; revised 7/23/04; accepted 8/18/04.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Hayes JD, Pulford DJ. 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 1995;30:445–600.[Medline]
  2. Ryberg D, Skaug V, Hewer A, et al. Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis 1997;18:1285–9.[Abstract/Free Full Text]
  3. Hallier E, Schroder KR, Asmuth K, Dommermuth A, Aust B, Goergens HW. Metabolism of dichloromethane (methylene chloride) to formaldehyde in human erythrocytes: influence of polymorphism of glutathione transferase theta (GST T1-1). Arch Toxicol 1994;68:423–7.[CrossRef][Medline]
  4. Sherratt PJ, Pulford DJ, Harrison DJ, Green T, Hayes JD. Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse. Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human. Biochem J 1997;326:837–46.
  5. Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997;6:733–43.[Abstract/Free Full Text]
  6. Sato K. Glutathione transferases as markers of preneoplasia and neoplasia. Adv Cancer Res 1989;52:205–55.[Medline]
  7. Gajewska J, Szczypka M. Role of pi form of glutathione S-transferase (GST-pi) in cancer: a minireview. Mater Med Pol 1992;24:45–9.[Medline]
  8. Lee WH, Morton RA, Epstein JI, et al. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci U S A 1994;91:11733–7.[Abstract/Free Full Text]
  9. Millar DS, Ow KK, Paul CL, Russell PJ, Molloy PL, Clark SJ. Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer. Oncogene 1999;18:1313–24.[CrossRef][Medline]
  10. Harries LW, Stubbins MJ, Forman D, Howard GC, Wolf CR. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997;18:641–4.[Abstract/Free Full Text]
  11. Zimniak P, Nanduri B, Pikula S, et al. Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties. Eur J Biochem 1994;224:893–9.[Medline]
  12. Hu X, Xia H, Srivastava SK, et al. Catalytic efficiencies of allelic variants of human glutathione S-transferase P1-1 toward carcinogenic anti-diol epoxides of benzo[c]phenanthrene and benzo[g]chrysene. Cancer Res 1998;58:5340–3.[Abstract/Free Full Text]
  13. Murata M, Shiraishi T, Fukutome K, et al. Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan. Jpn J Clin Oncol 1998;28:657–60.[Abstract/Free Full Text]
  14. Acevedo C, Opazo JL, Huidobro C, Cabezas J, Iturrieta J, Quinones Sepulveda L. Positive correlation between single or combined genotypes of CYP1A1 and GSTM1 in relation to prostate cancer in Chilean people. Prostate 2003;57:111–7.[CrossRef][Medline]
  15. Autrup JL, Thomassen LH, Olsen JH, Wolf H, Autrup H. Glutathione S-transferases as risk factors in prostate cancer. Eur J Cancer Prev 1999;8:525–32.[Medline]
  16. Steinhoff C, Franke KH, Golka K, et al. Glutathione transferase isozyme genotypes in patients with prostate and bladder carcinoma. Arch Toxicol 2000;74:521–6.[CrossRef][Medline]
  17. Nam RK, Zhang WW, Trachtenberg J, et al. Comprehensive assessment of candidate genes and serological markers for the detection of prostate cancer. Cancer Epidemiol Biomarkers Prev 2003;12:1429–37.[Abstract/Free Full Text]
  18. Kote-Jarai Z, Easton D, Edwards SM, et al. Relationship between glutathione S-transferase M1, P1 and T1 polymorphisms and early onset prostate cancer. Pharmacogenetics 2001;11:325–30.[CrossRef][Medline]
  19. Nakazato H, Suzuki K, Matsui H, et al. Association of genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) with familial prostate cancer risk in a Japanese population. Anticancer Res 2003;23:2897–902.[Medline]
  20. Gsur A, Haidinger G, Hinteregger S, et al. Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 and GSTT1) and prostate-cancer risk. Int J Cancer 2001;95:152–5.[CrossRef][Medline]
  21. Kidd LC, Woodson K, Taylor PR, Albanes D, Virtamo J, Tangrea JA. Polymorphisms in glutathione-S-transferase genes (GST-M1, GST-T1 and GST-P1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study. Eur J Cancer Prev 2003;12:317–20.[Medline]
  22. Kelada SN, Kardia SL, Walker AH, Wein AJ, Malkowicz SB, Rebbeck TR. The glutathione S-transferase-mu and -theta genotypes in the etiology of prostate cancer: genotype-environment interactions with smoking. Cancer Epidemiol Biomarkers Prev 2000;9:1329–34.[Abstract/Free Full Text]
  23. Medeiros R, Vasconcelos A, Costa S, et al. Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms. Prostate 2004;58:414–20.[CrossRef][Medline]
  24. Murata M, Watanabe M, Yamanaka M, et al. Genetic polymorphisms in cytochrome P450 (CYP) 1A1, CYP1A2, CYP2E1, glutathione S-transferase (GST) M1 and GSTT1 and susceptibility to prostate cancer in the Japanese population. Cancer Lett 2001;165:171–7.[CrossRef][Medline]
  25. Luscombe CJ, French ME, Liu S, et al. Glutathione S-transferase GSTP1 genotypes are associated with response to androgen ablation therapy in advanced prostate cancer. Cancer Detect Prev 2002;26:376–80.[CrossRef][Medline]
  26. Jeronimo C, Varzim G, Henrique R, et al. I105V polymorphism and promoter methylation of the GSTP1 gene in prostate adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2002;11:445–50.[Abstract/Free Full Text]
  27. Wadelius M, Autrup JL, Stubbins MJ, et al. Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. Pharmacogenetics 1999;9:333–40.[Medline]
  28. Shepard TF, Platz EA, Kantoff PW, et al. No association between the I105V polymorphism of the glutathione S-transferase P1 gene (GSTP1) and prostate cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev 2000;9:1267–8.[Free Full Text]
  29. Ntais C, Polycarpou A, Ioannidis JPA. Association of CYP17 gene polymorphism with the risk of prostate cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2003;12:120–6.[Abstract/Free Full Text]
  30. Ntais C, Polycarpou A, Ioannidis JPA. SRD5A2 gene polymorphisms and the risk of prostate cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2003;12:618–24.[Abstract/Free Full Text]
  31. Ntais C, Polycarpou A, Ioannidis JPA. Vitamin D receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2003;12:1395–402.[Abstract/Free Full Text]
  32. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med 1997;127:820–6.[Abstract/Free Full Text]
  33. Lau J, Antman EM, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med 1992;327:248–54.[Abstract]
  34. Ioannidis JP, Contopoulos-Ioannidis DG, Lau J. Recursive cumulative meta-analysis: a diagnostic for the evolution of total randomized evidence from group and individual patient data. J Clin Epidemiol 1999;52:281–91.[CrossRef][Medline]
  35. Ioannidis JP, Lau J. Evolution of treatment effects over time: empirical insight from recursive cumulative metaanalyses. Proc Natl Acad Sci USA 2001;98:831–6.[Abstract/Free Full Text]
  36. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet 2001;29:306–9.[CrossRef][Medline]
  37. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.[CrossRef][Medline]
  38. Ioannidis JP, Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG. Genetic associations in big vs. small studies: an empirical evaluation. Lancet 2003;361:567–71.[CrossRef][Medline]
  39. Ioannidis JP. Genetic associations: false or true? Trends Mol Med 2003;9:135–8.[CrossRef][Medline]
  40. Trikalinos T, Ntzani EE, Contopoulos-Ioannidis DG, Ioannidis JP. Establishment of genetic associations for complex diseases is independent of early study findings. Eur J Hum Genet 2004;12:762–9.[CrossRef][Medline]
  41. Listowsky I, Abramovitz M, Homma H, Niitsu Y. Intracellular binding and transport of hormones and xenobiotics by glutathione-S-transferases. Drug Metab Rev 1988;19:305–18.[Medline]
  42. Hsing AW. Hormones and prostate cancer: what's next? Epidemiol Rev 2001;23:42–58.[Free Full Text]
  43. Hsing AW, Reichardt JK, Stanczyk FZ. Hormones and prostate cancer: current perspectives and future directions. Prostate 2002;52:213–35.[CrossRef][Medline]
  44. Ntais C, Polycarpou A, Tsatsoulis A. Molecular epidemiology of prostate cancer: androgens and polymorphisms in androgen-related genes. Eur J Endocrinol 2003;149:469–77.[Abstract]
  45. Makridakis NM, Reichardt JK. Molecular epidemiology of hormone-metabolic loci in prostate cancer. Epidemiol Rev 2001;23:24–9.[Free Full Text]
  46. Egan KM, Cai Q, Shu XO, et al. Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis. Cancer Epidemiol Biomarkers Prev 2004;13:197–204.[Abstract/Free Full Text]
  47. Ye Z, Parry JM. A meta-analysis of 20 case-control studies of the glutathione S-transferase M1 (GSTM1) status and colorectal cancer risk. Med Sci Monit 2003;9:SR83–91.[Medline]
  48. Hashibe M, Brennan P, Strange RC, et al. Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev 2003;12:1509–17.[Abstract/Free Full Text]
  49. Benhamou S, Lee WJ, Alexandrie AK, et al. Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk. Carcinogenesis 2002;23:1343–50.[Abstract/Free Full Text]
  50. Engel LS, Taioli E, Pfeiffer R, et al. Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review. Am J Epidemiol 2002;156:95–109.[Abstract/Free Full Text]
  51. Ioannidis JP, Rosenberg PS, Goedert JJ, O'Brien TR. Commentary: meta-analysis of individual participants' data in genetic epidemiology. Am J Epidemiol 2002;156:204–10.[Free Full Text]



This article has been cited by other articles:


Home page
 Clin. Chem.Home page
C. M. Sturgeon, M. J. Duffy, U.-H. Stenman, H. Lilja, N. Brunner, D. W. Chan, R. Babaian, R. C. Bast Jr., B. Dowell, F. J. Esteva, et al.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers
Clin. Chem., December 1, 2008; 54(12): e11 - e79.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
N. Hokaiwado, F. Takeshita, A. Naiki-Ito, M. Asamoto, T. Ochiya, and T. Shirai
Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells
Carcinogenesis, June 1, 2008; 29(6): 1134 - 1138.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
E. Kellen, M. Hemelt, K. Broberg, K. Golka, V. N. Kristensen, R. J. Hung, G. Matullo, R. D. Mittal, S. Porru, A. Povey, et al.
Pooled Analysis and Meta-analysis of the Glutathione S-Transferase P1 Ile 105Val Polymorphism and Bladder Cancer: A HuGE-GSEC Review
Am. J. Epidemiol., June 1, 2007; 165(11): 1221 - 1230.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
J. M. Cunningham, S. J. Hebbring, S. K. McDonnell, M. S. Cicek, G. B. Christensen, L. Wang, S. J. Jacobsen, J. R. Cerhan, M. L. Blute, D. J. Schaid, et al.
Evaluation of Genetic Variations in the Androgen and Estrogen Metabolic Pathways as Risk Factors for Sporadic and Familial Prostate Cancer
Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 969 - 978.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ntais, C.
Right arrow Articles by Ioannidis, J. P.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ntais, C.
Right arrow Articles by Ioannidis, J. P.A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online