Reduced DNA repair capacity for removing tobacco carcinogen-induced DNA adducts contributes to risk of head and neck cancer but not tumor characteristics.
OBJECTIVE
Although cigarette smoking and alcohol use are known risk factors for squamous cell carcinoma of head and neck (SCCHN), only a few exposed individuals develop this disease, suggesting an individual susceptibility. In this study, we investigated the associations between genetically determined DNA repair capacity (DRC) for removing tobacco-induced DNA adducts and risk of SCCHN and tumor characteristics.


METHODS
We measured DRC in cultured T lymphocytes using the host-cell reactivation assay in a hospital-based case-control study of 744 SCCHN patients and 753 age-, sex-, and ethnicity-matched cancer-free controls recruited from The University of Texas M.D. Anderson Cancer Center.


RESULTS
Patients with SCCHN had significantly lower mean DRC (8.84% +/- 2.68%) than controls (9.97% +/- 2.61%; P < 0.0001), and the difference accounted for approximately 2-fold increased risk of SCCHN [adjusted odds ratio (OR), 1.91; 95% confidence interval (CI), 1.52-2.40] after adjustment for other covariates. Compared with the highest DRC quartile of controls, this increased risk was dose dependent (second highest quartile: OR, 1.40; 95% CI, 0.99-1.98; third quartile: OR, 1.87; 95% CI, 1.34-2.62; and fourth quartile: OR, 2.76; 95% CI, 1.98-3.84, respectively; P(trend) < 0.0001). We also assessed the performance of DRC in risk prediction models by calculating the area of under the receiver operating characteristic curve. The addition of DRC to the model significantly improved the sensitivity of the expanded model. However, we did not find the association between DRC and tumor sites and stages.


CONCLUSIONS
DRC is an independent susceptibility biomarker for SCCHN risk but not a tumor marker.
Wang
Li-E
LE
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Hu
Zhibin
Z
Sturgis
Erich M
EM
Spitz
Margaret R
MR
Strom
Sara S
SS
Amos
Christopher I
CI
Guo
Zhaozheng
Z
Qiao
Yawei
Y
Gillenwater
Ann Marie
AM
Myers
Jeffrey N
JN
Clayman
Gary L
GL
Weber
Randal S
RS
El-Naggar
Adel K
AK
Mao
Li
L
Lippman
Scott M
SM
Hong
Waun Ki
WK
Wei
Qingyi
Q
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult; D014026:Nicotiana
D002273:Carcinogens; D018736:DNA Adducts