In vitro BPDE-induced DNA adducts in peripheral lymphocytes as a risk factor for squamous cell carcinoma of the head and neck.
The level of DNA adducts under the same conditions of carcinogen exposure and cell proliferation reflects an integrated measure of carcinogen metabolism and DNA repair. Therefore, such DNA adduct levels have the potential to be a biomarker for susceptibility to chemical carcinogenesis. In a pilot study of 91 patients with squamous cell carcinomas of the head and neck and 115 controls who were frequency matched by age, sex, ethnicity, and smoking status, we applied a newly developed in vitro assay of benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in short-term peripheral lymphocytes cultures. Levels of BPDE-DNA adducts were found to be significantly higher in cases than in controls (mean +/- SD, 76.8 +/- 77.4/10(7) and 47.1 +/- 48.0/10(7) nucleotides, respectively; p < 0.001). Using the median level of control values (35/10(7)) as the cut-off point, about 66% of cases were distributed above this level. Logistic regression analysis revealed that the level of BPDE-induced DNA adducts was an independent risk factor (odds ratio = 2.22; 95% confidence interval = 1.22--4.04) after adjustment for age, sex and smoking status. Further stratified analyses showed that levels of the induced adducts between cases and controls were significantly higher in both age groups, that is, younger or older than 60, as well as in both men and women. Smoking had a positive effect on the induced adducts. The highest level of induced adducts was seen in current smokers, then former smokers and non-smokers. There was a statistically significant dose--response relationship between the quartile levels of BPDE-induced DNA adducts and the risk of head and neck cancer (trend test, p = 0.003). Despite the relatively small sample size, the association of BPDE-induced DNA adducts and cancer risk suggests that this assay has the potential to complement with other biomarkers in identifying individuals at increased risk of developing tobacco-related cancers.
Li
D
D
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. dli@mdanderson.org
Firozi
P F
PF
Chang
P
P
Wang
L E
LE
Xiong
P
P
Sturgis
E M
EM
Eicher
S A
SA
Spitz
M R
MR
Hong
W K
WK
Wei
Q
Q
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism* / Q000494:pharmacology*; D015415:Biomarkers; D002273:Carcinogens / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D018736:DNA Adducts / Q000187:drug effects* / Q000378:metabolism*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects*; D004198:Disease Susceptibility; D005260:Female; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D015415:Biomarkers; D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide