White blood cell DNA adducts, smoking, and NAT2 and GSTM1 genotypes in bladder cancer: a case-control study.
We conducted a case-control study on 114 bladder cancer patients and 46 hospital controls. DNA adducts were measured in WBCs by 32P postlabeling and showed no association with smoking habits and the glutathione-S-transferase M1 genotype. A strong association between adduct levels and the N-acetyltransferase (NAT2) genotype was found (P = 0.0002). The NAT2 genotype was associated in a nonstatistically significant way to the case-control status (odds ratio, 1.6; 95% confidence interval, 0.8-3.2). In a logistic regression model, the log of DNA adduct levels was associated in a highly significant way to the risk of bladder cancer (regression coefficient, 0.75; P = 0.0006), independently of smoking habits. Using the median of DNA adducts (RAL, 0.3) as a cutoff point, the odds ratio for the risk of bladder cancer was 4.1 (age-adjusted; 95% confidence interval, 1.9-9.0). Our study suggests that sources other than tobacco smoke contribute to the formation of aromatic DNA adducts in WBCs. The role of WBC-DNA adducts in predicting bladder cancer is still to be clarified.
Peluso
M
M
Servizio di Oncologia Sperimentale, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Airoldi
L
L
Armelle
M
M
Martone
T
T
Coda
R
R
Malaveille
C
C
Giacomelli
G
G
Terrone
C
C
Casetta
G
G
Vineis
P
P
D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000097:blood*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007962:Leukocytes / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000201:enzymology / Q000235:genetics*
D018736:DNA Adducts; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase