Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Homozygous deletions of UGT2B17 modifies effects of smoking on TP53-mutations and relapse of head and neck carcinoma

Authors: Aki Mafune, Takanori Hama, Toshihito Suda, Yutaka Suzuki, Masahiro Ikegami, Chikako Sakanashi, Satoko Imai, Akio Nakashima, Takashi Yokoo, Kota Wada, Hiromi Kojima, Mitsuyoshi Urashima

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Smoking induces oncogenic TP53-mutations in head and neck squamous cell carcinomas (HNSCCs). Disruptive mutations of TP53-gene and expression of p16 protein [p16 (+)] in tumor tissue associate with worse and better prognosis, respectively. UDP-glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17) detoxifies smoking-related metabolites. Differences among ethnic groups in UGT2B17 are extremely high. Homozygous deletions of UGT2B17 gene (UGT2B17-deletion) are a common copy number variant (CNV) among Japanese, but not a common CNV among Africans and Europeans. Thus, we examined Japanese patients with HNSCC to explore if UGT2B17-deletion and/or p16 (+) modify effects of smoking on TP53-mutations and affect relapse.

Methods

We conducted a posthoc analysis of a prospective cohort. Polymerase chain reaction, immunohistochemistry, and direct sequencing were used to determine UGT2B17-deletion, p16 (+), and detailed TP53-mutations, respectively.

Results

UGT2B17-deletion was observed in 80% of this study population. For this 80%, TP53-mutations were significantly more common among smokers than non-smokers (P = 0.0016), but this difference between smokers and nonsmokers was not significant for the 20% with UGT2B17. In patients with UGT2B17-deletion and p16 (+), simultaneously, TP53-mutations were much more common among smokers than among non-smokers (81% versus 17%; P = 0.0050). Patients with both UGT2B17-deletion and disruptive TP53-mutations had higher relapse rates than other patients (hazard ratio, 2.22; 95% confidence interval, 1.30 to 3.80, P = 0.004) in a stepwise method.

Conclusions

These results suggest that UGT2B17-deletion interacting with p16 (+) may modify effects of smoking on TP53-mutations and may further interact with the disruptive TP53-mutations to raise relapse rates among Japanese patients with HNSCC.
Literature
1.
2.
Hukkanen J, Jacob 3rd P, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57:79–115.CrossRefPubMed
3.
Caldwell WS, Greene JM, Byrd GD, Chang KM, Uhrig MS, de Bethizy JD, et al. Characterization of the glucuronide conjugate of cotinine: a previously unidentified major metabolite of nicotine in smokers’ urine. Chem Res Toxicol. 1992;5:280–5.CrossRefPubMed
4.
Lazarus P, Zheng Y, Runkle EA, Muscat JE, Wiener D. Genotype-phenotype correlation between the polymorphic UGT2B17-gene deletions and NNAL glucuronidation activities in human liver microsomes. Pharmacogenet Genomics. 2005;15:769–78.CrossRefPubMed
5.
Gallagher CJ, Muscat JE, Hicks AN, Zheng Y, Dyer AM, Chase GA, et al. The UDP-glucuronosyltransferase 2B17 gene deletions polymorphism: sex-specific association with urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronidation phenotype and risk for lung cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:823–8.CrossRefPubMed
6.
7.
LLubin JH, Purdue M, Kelsey K, Zhang ZF, Winn D, Wei Q, et al. Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies. Am J Epidemiol. 2009;170:937–47.CrossRef
8.
Brennan JA, Boyle JO, Koch WM, Goodman SN, Hurban RH, Eby YJ, et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med. 1995;332:712–7.CrossRefPubMed
9.
Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157–60.CrossRefPubMedPubMedCentral
10.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333:1154–7.CrossRef
11.
Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, et al. TP53-mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007;357:2552–61.CrossRefPubMedPubMedCentral
12.
Rischin D, Young RJ, Fisher R, Fox SB, Le QT, Peters LJ, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28:4142–8.CrossRefPubMedPubMedCentral
13.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.CrossRefPubMedPubMedCentral
14.
Urashima M, Hama T, Suda T, Suzuki Y, Ikegami M, Sakanashi C, et al. Distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma. PLoS One. 2013;8:e80828.CrossRefPubMedPubMedCentral
15.
Chen G, Giambrone Jr NE, Dluzen DF, Muscat JE, Berg A, Gallagher CJ, et al. Glucuronidation genotypes and nicotine metabolic phenotypes: importance of functional UGT2B10 and UGT2B17 polymorphisms. Cancer Res. 2010;70:7543–52.CrossRefPubMedPubMedCentral
16.
17.
18.
Yang TL, Chen XD, Guo Y, Lei SF, Wang JT, Zhou Q, et al. Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis. Am J Hum Genet. 2008;83:663–74.CrossRefPubMedPubMedCentral
19.
Chew S, Mullin BH, Lewis JR, Spector TD, Prince RL, Wilson SG. Homozygous deletion of the UGT2B17 gene is not associated with osteoporosis risk in elderly Caucasian women. Osteoporos Int. 2011;22:1981–6.CrossRefPubMed
20.
21.
Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat. 2007;28:622–9.CrossRefPubMed
22.
Gruber M, Le T, Filipits M, Gsur A, Mannhalter C, Jäger U, et al. UDP-glucuronosyltransferase 2B17 genotype and the risk of lung cancer among Austrian Caucasians. Cancer Epidemiol. 2013;37:625–8.CrossRefPubMed
23.
Okano M, Ueda T, Nishitani Y, Kano H, Ikekita A, Kageyama S. UDP-glucuronosyltransferase 2B17 genotyping in Japanese athletes and evaluation of the current sports drug testing for detecting testosterone misuse. Drug Test Anal. 2013;5:166–81.CrossRefPubMed
24.
Dyson N, Howley PM, Münger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989;243(4893):934–7.CrossRefPubMed
Metadata
Title
Homozygous deletions of UGT2B17 modifies effects of smoking on TP53-mutations and relapse of head and neck carcinoma
Authors
Aki Mafune
Takanori Hama
Toshihito Suda
Yutaka Suzuki
Masahiro Ikegami
Chikako Sakanashi
Satoko Imai
Akio Nakashima
Takashi Yokoo
Kota Wada
Hiromi Kojima
Mitsuyoshi Urashima
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1220-2

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

Association between praziquantel treatment and cholangiocarcinoma: a hospital-based matched case–control study

Research article

Population attributable risks of oral cavity cancer to behavioral and medical risk factors in France: results of a large population-based case–control study, the ICARE study

Research article

Systematic review of the predictive effect of MSI status in colorectal cancer patients undergoing 5FU-based chemotherapy

Research article

Serum CD26 levels in patients with gastric cancer: a novel potential diagnostic marker

Research article

Detection of morphologic alterations in rectal carcinoma following preoperative radiochemotherapy based on multiphoton microscopy imaging

Research article

A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits