GSTT1 Polymorphism and Prostate Cancer Risk
GSTT1 Polymorphism and Prostate Cancer Risk
A total of 73 studies were retrieved from the databases independently by 2 investigators (T.-B.Z. and Z.-P.J.). The results were compared, and disagreements over 3 articles were resolved by discussion with Y.-H.Q. The information on the first author's surname, year of publication, location of the study, subjects' ethnicity, source of the control group, and the number of cases and controls for the GSTT1 genotype was in agreement. The data were entered into Cochrane Review Manager, version 5, and the results from both investigators were the same. An overview of the selection procedure is presented in Figure 1. Thirty-eight studies reporting on the relationship between GSTT1 polymorphism and prostate cancer susceptibility were ultimately included in this meta-analysis (Figure 1); all reports were published in English ( Table 1 ). The data of interest were extracted as summarized in Table 1 . The included studies contained a total of 9,752 patients with prostate cancer and 10,530 controls.
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Figure 1.
Flow chart for study recruitment into the meta-analysis of the glutathione S-transferase theta 1 gene (GSTT1) polymorphism and prostate cancer relationship, 1999–2012.
The average distribution frequency of the GSTT1 null genotype in the prostate cancer group was 28.36%, and the average frequency in the control group was 25.97%. The average distribution frequency of the GSTT1 null genotype in the case group was similar to the control group (28.36%/25.97% = 1.09). The average distribution of the GSTT1 null genotype frequency in Caucasians was 26.36% for cases and 22.31% for controls.
The results from this meta-analysis showed clear trends with respect to the association between the GSTT1 null genotype and the risk of developing prostate cancer. No association between the GSTT1 null genotype and an increased prostate cancer risk could be established in the overall population (odds ratio (OR) = 1.11, 95% confidence interval (CI): 0.97, 1.27; P = 0.13; Figure 2 and Table 2 ).
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Figure 2.
Results from prospective studies of the glutathione S-transferase theta 1 gene null genotype and prostate cancer risk in the overall population, 1999–2012. The summary estimate (diamond) was calculated using a random-effects model. Odds ratios (ORs) less than 1 favor cases; ORs greater than 1 favor controls. Assessment of heterogeneity: τ = 0.11, χ = 125.36, df = 37 (P < 0.00001), I = 70%. Test for overall effect: Z = 1.51 (P = 0.13). Bars, 95% confidence intervals (CIs).
Conversely, a clear association of the GSTT1 null genotype and prostate cancer risk could be established for Caucasians (OR = 1.24, 95% CI: 1.03, 1.48; P = 0.02; Figure 3 and Table 2 ). These results are in agreement with data from general epidemiologic and clinical observations that show a significantly higher prevalence of prostate cancer in Western and industrialized countries.
(Enlarge Image)
Figure 3.
Results from prospective studies of the glutathione S-transferase theta 1 gene null genotype and prostate cancer risk in the Caucasian population, 1999–2012. The summary estimate presented (diamond) was calculated using a random-effects model. Odds ratios (ORs) less than 1 favor cases; ORs greater than 1 favor controls. Assessment of heterogeneity: τ = 0.13, χ = 73.76, df = 23 (P < 0.00001), I = 69%. Test for overall effect: Z = 2.29 (P = 0.02). Bars, 95% confidence intervals (CIs).
We performed sensitivity analysis for the relationship between the GSTT1 null genotype and prostate cancer risk according to the source of the controls (i.e., population- or hospital-based). We found that the results were similar to those obtained from the main analysis ( Table 2 ). Similarly, sensitivity analysis for the relationship between the GSTT1 null genotype and prostate cancer risk according to sample size of cases or controls (i.e., <100 or ≥100 subjects) produced results that were similar to those of the main analysis ( Table 2 ). Overall, no significant deviations were found between the main analysis and sensitivity analyses.
Publication bias was established for the overall population (Begg P = 0.131, Egger P = 0.406) (Figure 4), for Caucasians (Begg P = 0.673, Egger P = 0.117), for the sample size of cases or controls (≥100 subjects) (Begg P = 0.020, Egger P = 0.013), for population-based controls (Begg P = 0.128, Egger P = 0.025), and for hospital-based controls (Begg P = 0.063, Egger P = 0.144).
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Figure 4.
Begg's funnel plots with pseudo 95% confidence limits. Evaluation of publication bias for the association of the glutathione S-transferase theta 1 gene null genotype with prostate cancer risk in the overall population, 1999–2012. OR, odds ratio; SE, standard error.
Results
Study Characteristics
A total of 73 studies were retrieved from the databases independently by 2 investigators (T.-B.Z. and Z.-P.J.). The results were compared, and disagreements over 3 articles were resolved by discussion with Y.-H.Q. The information on the first author's surname, year of publication, location of the study, subjects' ethnicity, source of the control group, and the number of cases and controls for the GSTT1 genotype was in agreement. The data were entered into Cochrane Review Manager, version 5, and the results from both investigators were the same. An overview of the selection procedure is presented in Figure 1. Thirty-eight studies reporting on the relationship between GSTT1 polymorphism and prostate cancer susceptibility were ultimately included in this meta-analysis (Figure 1); all reports were published in English ( Table 1 ). The data of interest were extracted as summarized in Table 1 . The included studies contained a total of 9,752 patients with prostate cancer and 10,530 controls.
(Enlarge Image)
Figure 1.
Flow chart for study recruitment into the meta-analysis of the glutathione S-transferase theta 1 gene (GSTT1) polymorphism and prostate cancer relationship, 1999–2012.
The average distribution frequency of the GSTT1 null genotype in the prostate cancer group was 28.36%, and the average frequency in the control group was 25.97%. The average distribution frequency of the GSTT1 null genotype in the case group was similar to the control group (28.36%/25.97% = 1.09). The average distribution of the GSTT1 null genotype frequency in Caucasians was 26.36% for cases and 22.31% for controls.
Association of the GSTT1 Null Genotype With Prostate Cancer Susceptibility
The results from this meta-analysis showed clear trends with respect to the association between the GSTT1 null genotype and the risk of developing prostate cancer. No association between the GSTT1 null genotype and an increased prostate cancer risk could be established in the overall population (odds ratio (OR) = 1.11, 95% confidence interval (CI): 0.97, 1.27; P = 0.13; Figure 2 and Table 2 ).
(Enlarge Image)
Figure 2.
Results from prospective studies of the glutathione S-transferase theta 1 gene null genotype and prostate cancer risk in the overall population, 1999–2012. The summary estimate (diamond) was calculated using a random-effects model. Odds ratios (ORs) less than 1 favor cases; ORs greater than 1 favor controls. Assessment of heterogeneity: τ = 0.11, χ = 125.36, df = 37 (P < 0.00001), I = 70%. Test for overall effect: Z = 1.51 (P = 0.13). Bars, 95% confidence intervals (CIs).
Conversely, a clear association of the GSTT1 null genotype and prostate cancer risk could be established for Caucasians (OR = 1.24, 95% CI: 1.03, 1.48; P = 0.02; Figure 3 and Table 2 ). These results are in agreement with data from general epidemiologic and clinical observations that show a significantly higher prevalence of prostate cancer in Western and industrialized countries.
(Enlarge Image)
Figure 3.
Results from prospective studies of the glutathione S-transferase theta 1 gene null genotype and prostate cancer risk in the Caucasian population, 1999–2012. The summary estimate presented (diamond) was calculated using a random-effects model. Odds ratios (ORs) less than 1 favor cases; ORs greater than 1 favor controls. Assessment of heterogeneity: τ = 0.13, χ = 73.76, df = 23 (P < 0.00001), I = 69%. Test for overall effect: Z = 2.29 (P = 0.02). Bars, 95% confidence intervals (CIs).
Sensitivity Analysis
We performed sensitivity analysis for the relationship between the GSTT1 null genotype and prostate cancer risk according to the source of the controls (i.e., population- or hospital-based). We found that the results were similar to those obtained from the main analysis ( Table 2 ). Similarly, sensitivity analysis for the relationship between the GSTT1 null genotype and prostate cancer risk according to sample size of cases or controls (i.e., <100 or ≥100 subjects) produced results that were similar to those of the main analysis ( Table 2 ). Overall, no significant deviations were found between the main analysis and sensitivity analyses.
Evaluation of Publication Bias
Publication bias was established for the overall population (Begg P = 0.131, Egger P = 0.406) (Figure 4), for Caucasians (Begg P = 0.673, Egger P = 0.117), for the sample size of cases or controls (≥100 subjects) (Begg P = 0.020, Egger P = 0.013), for population-based controls (Begg P = 0.128, Egger P = 0.025), and for hospital-based controls (Begg P = 0.063, Egger P = 0.144).
(Enlarge Image)
Figure 4.
Begg's funnel plots with pseudo 95% confidence limits. Evaluation of publication bias for the association of the glutathione S-transferase theta 1 gene null genotype with prostate cancer risk in the overall population, 1999–2012. OR, odds ratio; SE, standard error.
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