Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review.
Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians results in a lack of GSTM1 enzyme activity. Most studies examining the relation between bladder cancer and GSTM1 have reported an increased risk associated with a lack of GSTM1 activity. The authors performed meta- and pooled analyses of published and unpublished, case-control, genotype-based studies that examined this association (17 studies, 2,149 cases, 3,646 controls) and excluded studies conducted in populations with a high prevalence of exposure to known bladder cancer risk factors other than tobacco smoke. Using random effects models in the meta-analysis, the authors obtained a summary odds ratio of 1.44 (95% confidence interval (CI): 1.23, 1.68) for GSTM1 null status with all studies included. Results from studies with at least 100 cases and 100 controls produced a summary odds ratio of 1.42 (95% CI: 1.26, 1.60). Pooled analyses using original data sets from 10 studies (1,496 cases and 1,444 controls) and adjusting for age, sex, and race produced similar results. There was no evidence of multiplicative interaction between the GSTM1 null genotype and ever smoking in relation to bladder cancer, although there was a suggestion of additive interaction (additive interaction = 0.45, 95% CI: -0.03, 0.93). These results indicate that, among populations studied to date, GSTM1 null status is associated with a modest increase in the risk of bladder cancer.
Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7240, USA. engell@mail.nih.gov
Lawrence S
LS
Engel
Emanuela
E
Taioli
Ruth
R
Pfeiffer
Montserrat
M
Garcia-Closas
Pamela M
PM
Marcus
Qing
Q
Lan
Paolo
P
Boffetta
Paolo
P
Vineis
Herman
H
Autrup
Douglas A
DA
Bell
Robert A
RA
Branch
Jürgen
J
Brockmöller
Ann K
AK
Daly
Susan R
SR
Heckbert
Ivan
I
Kalina
Daehee
D
Kang
Takahiko
T
Katoh
Amalia
A
Lafuente
Henry J
HJ
Lin
Marjorie
M
Romkes
Jack A
JA
Taylor
Nathaniel
N
Rothman
D001564:Benzo(a)pyrene / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D016022:Case-Control Studies; D016001:Confidence Intervals; D005060:Europe / Q000453:epidemiology; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007723:Korea / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism
D001564:Benzo(a)pyrene; D002273:Carcinogens; D005982:Glutathione Transferase