caa a22 4500 397562233 CHVBK 20180308164819.0 cr unu---uuuuu 161202e19960417xx s 000 0 eng 10.1093/jnci/88.8.530 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.8.530 Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma [Elektronische Daten] [Jacqueline Cloos, Margaret R. Spitz, Stimson P. Schantz, T. C. Hsu, Zuo-feng Zhang, Hilde Tobi, Boudewijn J. M. Braakhuis, Gordon B. Snow] Background: In addition to influences of exposure to carcinogenic compounds, the development of cancer may depend on an individual intrinsic cancer susceptibility. Biomarkers for cancer susceptibility can be powerful additions to epidemiologic analyses. Purpose: This multicenter, case—control analysis combines previously published data and new data to substantiate the value of mutagen sensitivity as a biomarker of susceptibility to head and neck squamous cell carcinoma and, more importantly, to gain insight into the interaction between susceptibility and exposure to carcinogens. Methods: Mutagen sensitivity (mean number of chromatid breaks per cell of cultured lymphocytes treated with bleomycin in the late S-G2 phase of the cell cycle) was determined in 313 patients with head and neck cancer and in 334 control subjects at two major U.S. medical institutions and one European institution, yielding a unique study population. The ages of the case and control subjects, as well as their history of use of tobacco and alcohol, were also recorded. The relationships between variables were analyzed by use of Student's t tests, Spearman's rank correlations, and multiple linear regression. For estimation of cancer risk, crude odds ratios (ORs) were measured and multiple logistic regression was performed. All P values were based on two-sided tests. Results: There were no differences across institutions in the distribution of mutagen sensitivity (Kruskal-Wallis test) for both case subjects and control subjects. Values for case subjects were consistently and significantly (P<.0001) higher than values for control subjects in the overall analyses. Age and tobacco or alcohol use did not influence the outcome in terms of mutagen-sensitivity values for either the case or the control subjects. A mean number of breaks per cell dichotomized at 1.0 was found to be the best predictor of a hypersensitive phenotype. For nonsensitive, heavy smokers, the OR was 11.5 (95% confidence interval [CI] = 5.0-26.6). This risk increased dramatically in mutagen-hypersensitive, heavy smokers to 44.6 (95% CI = 17.4-114.0). Multiple logistic regression analysis confirmed these results, and a significant trend was found (P<.01) for the dose-dependent increase in cancer risk by smoking. The consumption of alcohol potentiated the effects of smoking, resulting in an OR of 57.5 (95% CI = 17.5-188.0) in hypersensitive persons. Conclusions: Mutagen sensitivity was found to be a biomarker of cancer susceptibility. This study underscores the importance of utilizing both susceptibility markers and exposure data for the identification of persons at high risk of developing cancer. Implications: More accurate risk estimation can define susceptible subgroups who might be targeted for intensive behavioral interventions, surveillance through screening, and enrollment in chemoprevention programs. [J Natl Cancer Inst 1996;88:530-5] © Oxford University Press ARTICLES nationallicence Cloos Jacqueline Department of Otolaryngology/Head and Neck Surgery, Free University Hospital Amsterdam, The Netherlands aut Spitz Margaret R. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center Houston aut Schantz Stimson P. Department of Head and Neck Surgery. Memorial Sloan-Kettering Cancer Center New York, NY aut Hsu T. C. Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center Houston aut Zhang Zuo-feng Department of Epidemiology, Memorial Sloan-Kettering Cancer Center New York, NY aut Tobi Hilde Department of Epidemiology and Biostatistics, Free University Amsterdam, The Netherlands aut Braakhuis Boudewijn J. M. Department of Otolaryngology/Head and Neck Surgery, Free University Hospital Amsterdam, The Netherlands aut Snow Gordon B. Department of Otolaryngology/Head and Neck Surgery, Free University Hospital Amsterdam, The Netherlands aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/8(1996-04-17), 530-535 0027-8874 88:8<530 1996 88 jnci https://doi.org/10.1093/jnci/88.8.530 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.8.530 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cloos Jacqueline Department of Otolaryngology/Head and Neck Surgery, Free University Hospital Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Spitz Margaret R. Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center Houston aut NATIONALLICENCE 700 1- Schantz Stimson P. Department of Head and Neck Surgery. Memorial Sloan-Kettering Cancer Center New York, NY aut NATIONALLICENCE 700 1- Hsu T. C. Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center Houston aut NATIONALLICENCE 700 1- Zhang Zuo-feng Department of Epidemiology, Memorial Sloan-Kettering Cancer Center New York, NY aut NATIONALLICENCE 700 1- Tobi Hilde Department of Epidemiology and Biostatistics, Free University Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Braakhuis Boudewijn J. M. Department of Otolaryngology/Head and Neck Surgery, Free University Hospital Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Snow Gordon B. Department of Otolaryngology/Head and Neck Surgery, Free University Hospital Amsterdam, The Netherlands aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/8(1996-04-17), 530-535 0027-8874 88:8<530 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford