Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers

Citation
Sp. Schantz et al., Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers, CARCINOGENE, 21(6), 2000, pp. 1239-1246
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
21
Issue
6
Year of publication
2000
Pages
1239 - 1246
Database
ISI
SICI code
0143-3334(200006)21:6<1239:MSAEEA>2.0.ZU;2-J
Abstract
The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carc inoma (HNSCC). Furthermore, this interplay may determine not only the proba bility of cancer development but also the biologic characteristics of the t umor once it occurs. To better understand the relationship of mutagen sensi tivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we e xamined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 micro satellite markers. Mutagen sensitivity was determined in vitro by quantitat ing bleomycin-induced chromatid breaks utilizing peripheral blood lympocyte s from respective patients. Forty-six of the 58 invasive cancers showed all elic loss at one or more loci, Consistent with previous investigations, thr ee discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21.2, a nd 3p25.1-26.1. The frequency and types of deletions were dependent upon to bacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast , heavy alcohol use when combined with tobacco use was associated with whol e-arm loss of 3p rather than identifiable site-specific damage. Furthermore , this combined influence of alcohol and tobacco exposures on whole-arm los s was most apparent in those patients who expressed mutagen-sensitivity; th e odds ratio of whole-arm loss increasing from 2.67 (95% CI 0.21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive, An asses sment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node me tastases and advanced stage disease than patients with partial losses. Resu lts indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic l osses in head and neck cancers as well as the behavior of disease once it d evelops.