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Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck.
Clin Cancer Res. 1998 Jul; 4(7):1773-8.CC

Abstract

Genetic susceptibility appears to modulate an individual's risk of tobacco-induced carcinoma. One biomarker of such susceptibility, chromatid breaks induced in vitro in lymphocytes by the mutagen bleomycin, is an independent risk factor for several malignancies. To date, the more etiologically appropriate mutagen benzo(a)pyrene diol epoxide (BPDE) has only been used in one lung cancer study. Our objective was to evaluate the association between the BPDE-induced chromatid breaks per cell (b/c) values and the risk of squamous cell carcinoma of the head and neck (SCCHN) in a pilot case-control study. Blood samples were obtained from 60 SCCHN patients and 112 healthy controls matched for age, sex, ethnicity, and smoking status. After incubation and exposure to BPDE, metaphase spread slides were created, and the average b/c values were determined. Univariate analysis identified elevated BPDE-induced b/c values as a significant risk factor [P < 0.05, crude odds ratio (OR)=1.94, 95% confidence interval (CI)=1.00-3.74]. On multivariate analysis using logistic regression models and including age, sex, ethnicity, and smoking status, BPDE-induced b/c values remained an independent risk factor for disease (P < 0.05, adjusted OR=2.36, 95% CI=1.17-4.79). Furthermore, when b/c values were divided based on control values into low, medium, and high tertiles, there was a dose-response relationship: an adjusted OR of 1.28 (95% CI=0.49-3.33) for the middle tertile and an adjusted OR of 4.09 (95% CI=1.67-10.0) for the high tertile (trend test, P < 0.001). These findings suggest that high BPDE-induced b/c values in lymphocytes are an independent risk factor for SCCHN and a marker for genetic susceptibility to tobacco-induced carcinogenesis.

Authors+Show Affiliations

Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9676854

Citation

Wang, L E., et al. "Mutagen Sensitivity to Benzo(a)pyrene Diol Epoxide and the Risk of Squamous Cell Carcinoma of the Head and Neck." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 4, no. 7, 1998, pp. 1773-8.
Wang LE, Sturgis EM, Eicher SA, et al. Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck. Clin Cancer Res. 1998;4(7):1773-8.
Wang, L. E., Sturgis, E. M., Eicher, S. A., Spitz, M. R., Hong, W. K., & Wei, Q. (1998). Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 4(7), 1773-8.
Wang LE, et al. Mutagen Sensitivity to Benzo(a)pyrene Diol Epoxide and the Risk of Squamous Cell Carcinoma of the Head and Neck. Clin Cancer Res. 1998;4(7):1773-8. PubMed PMID: 9676854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck. AU - Wang,L E, AU - Sturgis,E M, AU - Eicher,S A, AU - Spitz,M R, AU - Hong,W K, AU - Wei,Q, PY - 1998/7/24/pubmed PY - 1998/7/24/medline PY - 1998/7/24/entrez SP - 1773 EP - 8 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 4 IS - 7 N2 - Genetic susceptibility appears to modulate an individual's risk of tobacco-induced carcinoma. One biomarker of such susceptibility, chromatid breaks induced in vitro in lymphocytes by the mutagen bleomycin, is an independent risk factor for several malignancies. To date, the more etiologically appropriate mutagen benzo(a)pyrene diol epoxide (BPDE) has only been used in one lung cancer study. Our objective was to evaluate the association between the BPDE-induced chromatid breaks per cell (b/c) values and the risk of squamous cell carcinoma of the head and neck (SCCHN) in a pilot case-control study. Blood samples were obtained from 60 SCCHN patients and 112 healthy controls matched for age, sex, ethnicity, and smoking status. After incubation and exposure to BPDE, metaphase spread slides were created, and the average b/c values were determined. Univariate analysis identified elevated BPDE-induced b/c values as a significant risk factor [P < 0.05, crude odds ratio (OR)=1.94, 95% confidence interval (CI)=1.00-3.74]. On multivariate analysis using logistic regression models and including age, sex, ethnicity, and smoking status, BPDE-induced b/c values remained an independent risk factor for disease (P < 0.05, adjusted OR=2.36, 95% CI=1.17-4.79). Furthermore, when b/c values were divided based on control values into low, medium, and high tertiles, there was a dose-response relationship: an adjusted OR of 1.28 (95% CI=0.49-3.33) for the middle tertile and an adjusted OR of 4.09 (95% CI=1.67-10.0) for the high tertile (trend test, P < 0.001). These findings suggest that high BPDE-induced b/c values in lymphocytes are an independent risk factor for SCCHN and a marker for genetic susceptibility to tobacco-induced carcinogenesis. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/9676854/Mutagen_sensitivity_to_benzo_a_pyrene_diol_epoxide_and_the_risk_of_squamous_cell_carcinoma_of_the_head_and_neck_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=9676854 DB - PRIME DP - Unbound Medicine ER -