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Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma

BACKGROUND: Tobacco and alcohol consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that smoking increased TP53 and other mutations in HNSCC; however, the effects of alcohol consumption on these genetic alterations remain unknown...

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Autores principales: Urashima, Mitsuyoshi, Hama, Takanori, Suda, Toshihito, Suzuki, Yutaka, Ikegami, Masahiro, Sakanashi, Chikako, Akutsu, Taisuke, Amagaya, Suguru, Horiuchi, Kazuhumi, Imai, Yu, Mezawa, Hidetoshi, Noya, Miki, Nakashima, Akio, Mafune, Aki, Kato, Takakuni, Kojima, Hiromi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835411/
https://www.ncbi.nlm.nih.gov/pubmed/24278325
http://dx.doi.org/10.1371/journal.pone.0080828
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author Urashima, Mitsuyoshi
Hama, Takanori
Suda, Toshihito
Suzuki, Yutaka
Ikegami, Masahiro
Sakanashi, Chikako
Akutsu, Taisuke
Amagaya, Suguru
Horiuchi, Kazuhumi
Imai, Yu
Mezawa, Hidetoshi
Noya, Miki
Nakashima, Akio
Mafune, Aki
Kato, Takakuni
Kojima, Hiromi
author_facet Urashima, Mitsuyoshi
Hama, Takanori
Suda, Toshihito
Suzuki, Yutaka
Ikegami, Masahiro
Sakanashi, Chikako
Akutsu, Taisuke
Amagaya, Suguru
Horiuchi, Kazuhumi
Imai, Yu
Mezawa, Hidetoshi
Noya, Miki
Nakashima, Akio
Mafune, Aki
Kato, Takakuni
Kojima, Hiromi
author_sort Urashima, Mitsuyoshi
collection PubMed
description BACKGROUND: Tobacco and alcohol consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that smoking increased TP53 and other mutations in HNSCC; however, the effects of alcohol consumption on these genetic alterations remain unknown. We explored the association between alcohol consumption and somatic copy-number alterations (SCNAs) across the whole genome in human papillomavirus (HPV)-negative HNSCCs, and compared with the effects of smoking on genetic alterations. METHODS: SCNA and TP53 mutations in tumor samples were examined by high-resolution comparative genomic hybridization microarray 180K and by direct sequencing, respectively, and statistically analyzed for associations with alcohol consumption and smoking during the 20 years preceding diagnosis of HNSCC. Probes with a corrected p-value (=q-value) less than 0.05 and fold change greater than 1.2 or less than -1.2 were considered statistically significant. RESULTS: A total of 248 patients with HNSCC were enrolled. In the HPV-negative patients (n=221), heavy alcohol consumption was significantly associated with SCNAs of oncogenes/oncosuppressors that were previously reported to occur frequently in HNSCCs: CDKN2A (q=0.005), FHIT (q=0.005), 11q13 region including CCND1, FADD and CTTN (q=0.005), ERBB2 (HER2) (q=0.009), 3q25-qter including CCNL1, TP63, DCUN1D1 and PIK3CA (q=0.014), and CSMD1 (q=0.019). But, TP53 mutations were not affected. In contrast, smoking was associated with increased risk of TP53 mutations, but did not induce any significant SCNAs of oncogenes/oncosuppressors. CONCLUSION: These results suggest that both alcohol consumption and smoking had distinct effects on genetic alterations in HNSCCs. Heavy alcohol consumption may trigger previously known and unknown SCNAs, but may not induce TP53 mutation. In contrast, smoking may induce TP53 mutation, but may not trigger any SCNAs.
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spelling pubmed-38354112013-11-25 Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma Urashima, Mitsuyoshi Hama, Takanori Suda, Toshihito Suzuki, Yutaka Ikegami, Masahiro Sakanashi, Chikako Akutsu, Taisuke Amagaya, Suguru Horiuchi, Kazuhumi Imai, Yu Mezawa, Hidetoshi Noya, Miki Nakashima, Akio Mafune, Aki Kato, Takakuni Kojima, Hiromi PLoS One Research Article BACKGROUND: Tobacco and alcohol consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that smoking increased TP53 and other mutations in HNSCC; however, the effects of alcohol consumption on these genetic alterations remain unknown. We explored the association between alcohol consumption and somatic copy-number alterations (SCNAs) across the whole genome in human papillomavirus (HPV)-negative HNSCCs, and compared with the effects of smoking on genetic alterations. METHODS: SCNA and TP53 mutations in tumor samples were examined by high-resolution comparative genomic hybridization microarray 180K and by direct sequencing, respectively, and statistically analyzed for associations with alcohol consumption and smoking during the 20 years preceding diagnosis of HNSCC. Probes with a corrected p-value (=q-value) less than 0.05 and fold change greater than 1.2 or less than -1.2 were considered statistically significant. RESULTS: A total of 248 patients with HNSCC were enrolled. In the HPV-negative patients (n=221), heavy alcohol consumption was significantly associated with SCNAs of oncogenes/oncosuppressors that were previously reported to occur frequently in HNSCCs: CDKN2A (q=0.005), FHIT (q=0.005), 11q13 region including CCND1, FADD and CTTN (q=0.005), ERBB2 (HER2) (q=0.009), 3q25-qter including CCNL1, TP63, DCUN1D1 and PIK3CA (q=0.014), and CSMD1 (q=0.019). But, TP53 mutations were not affected. In contrast, smoking was associated with increased risk of TP53 mutations, but did not induce any significant SCNAs of oncogenes/oncosuppressors. CONCLUSION: These results suggest that both alcohol consumption and smoking had distinct effects on genetic alterations in HNSCCs. Heavy alcohol consumption may trigger previously known and unknown SCNAs, but may not induce TP53 mutation. In contrast, smoking may induce TP53 mutation, but may not trigger any SCNAs. Public Library of Science 2013-11-20 /pmc/articles/PMC3835411/ /pubmed/24278325 http://dx.doi.org/10.1371/journal.pone.0080828 Text en © 2013 Urashima et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Urashima, Mitsuyoshi
Hama, Takanori
Suda, Toshihito
Suzuki, Yutaka
Ikegami, Masahiro
Sakanashi, Chikako
Akutsu, Taisuke
Amagaya, Suguru
Horiuchi, Kazuhumi
Imai, Yu
Mezawa, Hidetoshi
Noya, Miki
Nakashima, Akio
Mafune, Aki
Kato, Takakuni
Kojima, Hiromi
Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma
title Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma
title_full Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma
title_fullStr Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma
title_full_unstemmed Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma
title_short Distinct Effects of Alcohol Consumption and Smoking on Genetic Alterations in Head and Neck Carcinoma
title_sort distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835411/
https://www.ncbi.nlm.nih.gov/pubmed/24278325
http://dx.doi.org/10.1371/journal.pone.0080828
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