A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism

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SUMMARY

The purpose of this report is to review the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer. The review was performed on available studies on genetic polymorphisms and head and neck cancer (HNC) published in PubMed up to September 2011. 246 primary articles and 7 meta-analyses were published. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698).

RIASSUNTO

Lo scopo di questo lavoro è stato valutare la relazione esistente tra i polimorfismi dei geni coinvolti nella carcinogenesi testa- collo, nel metabolismo dell'alcool e nel controllo del ciclo cellulare e il rischio di sviluppare un tumore della testa e del collo (HNC). La revisione è stata effettuata su studi relativi ai polimorfismi genetici e al cancro testa collo (HNC) pubblicati su PubMed fino al settembre 2011. I risultati hanno mostrato l'esistenza di 246 articoli primari e 7 meta-analisi. Tra queste, una associazione statisticamente significativa è stata segnalata per la glutatione S-transferasi (GSTM1), glutatione S-transferasi (GSTT1) e Human microsomal epoxide hydrolase (EPHX1) geni. Un aumentato rischio di sviluppo del tumore testa collo è stato inoltre associato alla presenza della variante di P53 codone 72 Pro/ Pro, di ALDH2, e delle tre varianti del gene ADH: ADH1B (rs1229984), ADH7 (rs1573496) e ADH1C (rs698).

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Most cited references 148

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TP53 mutations and survival in squamous-cell carcinoma of the head and neck.

M Luana Poeta, Judith Manola, Meredith A. Goldwasser … (2007)

The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck. A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53-DNA complexes. TP53 mutational status was compared with clinical outcome. TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P=0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P=0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P=0.003). Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck. Copyright 2007 Massachusetts Medical Society.

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Two polymorphic variants of wild-type p53 differ biochemically and biologically.

Miranda Thomas, Ann Kalita, Sylvie Labrecque … (1999)

The wild-type p53 protein exhibits a common polymorphism at amino acid 72, resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg) at this position. Despite the difference that this change makes in the primary structure of the protein resulting in a difference in migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no differences in the biochemical or biological characteristics of these wild-type p53 variants have been reported. We have recently shown that p53Arg is significantly more susceptible than p53Pro to the degradation induced by human papillomavirus (HPV) E6 protein. Moreover, this may result in an increased susceptibility to HPV-induced tumors in homozygous p53Arg individuals. In further investigating the characteristics of these p53 variants, we now show that both forms are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner. However, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells. These observations may have implications for the development of cancers which harbor wild-type p53 sequences and possibly for the ability of such tumors to respond to therapy, depending on their p53 genotype.

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Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk.

David Zaridze, Michael D. McClean, Sergio Koifman … (2010)

Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

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Author and article information

Journal

Journal ID (nlm-ta): Acta Otorhinolaryngol Ital

Journal ID (iso-abbrev): Acta Otorhinolaryngol Ital

Journal ID (publisher-id): Pacini

Title: Acta Otorhinolaryngologica Italica

Publisher: Pacini Editore SpA

ISSN (Print): 0392-100X

ISSN (Electronic): 1827-675X

Publication date (Print): February 2012

Volume: 32

Issue: 1

Pages: 1-11

Affiliations

[1 ] Institute of Otorhinolaryngology, Università Cattolica del Sacro Cuore, Rome, Italy;

[2 ] Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy;

[3 ] IRCCS, San Raffaele Pisana, Rome, Italy

Author notes

Address for correspondence: Gabriella Cadoni, Ist. Otorinolaringoiatria, Università Cattolica Sacro Cuore, Policlinico A. Gemelli, largo A. Gemelli 8, 00168 Roma, Italy. Tel. +39 06 30154439. Email: gabriella.cadoni@ 123456rm.unicatt.it

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Publisher ID: Pacini

PMC ID: 3324962

PubMed ID: 22500060

SO-VID: 5841af1d-592c-48f5-bf8b-ab7b812c32f3

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/

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Most cited references 148

TP53 mutations and survival in squamous-cell carcinoma of the head and neck.

Two polymorphic variants of wild-type p53 differ biochemically and biologically.

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk.

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