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Distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma.

ABSTRACT: 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.

SUBMITTER: Urashima M

PROVIDER: S-EPMC3835411 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma.

Urashima Mitsuyoshi M Hama Takanori T Suda Toshihito T Suzuki Yutaka Y Ikegami Masahiro M Sakanashi Chikako C Akutsu Taisuke T Amagaya Suguru S Horiuchi Kazuhumi K Imai Yu Y Mezawa Hidetoshi H Noya Miki M Nakashima Akio A Mafune Aki A Kato Takakuni T Kojima Hiromi H

PloS one 20131120 11

<h4>Background</h4>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 th ...[more]

PMID: 24278325

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Project description:Background: The most important risk factors for head and neck squamous carcinoma (HNSCC) are tobacco smoking and alcohol consumption, while subgroups are caused by infection with human papillomaviruses (HPV) or Epstein-Barr virus (EBV). Here, we studied alterations of somatic copy-number in whole genome, p16 protein and TP53 mutations by alcohol drinking, smoking and viral infections. Methods: We conducted a prospective cohort study. DNA obtained from tumors and margin samples as well as peripheral blood was assayed by array comparative genomic hybridization using Agilent Whole Human Genome 180K. Mutations of p53 gene by direct sequencing, detection of HPV by polymerase-chain-reaction (PCR), quantification of EBV by reverse transcription-PCR and p16 immunohistochemical (IHC) staining were also performed. prospective cohort study: 225 tumor samples were analyzed by Agilent-022060 SurePrint G3 Human CGH miroarray 4x180K. Log2 Ratio (tumor sample DNA/normal DNA) were compared among none alcohol drinkers, moderate alcohol drinkers, heavy alcohol drinkers, none smokers, moderate smokers, heavy smokers and both. Sample characteristics weres scored as following; Human Papilloma Virus Infection (gene detected by PCR in tumor sample): positive=1; negative=0 p16 protein immunohistochemistry: positive=1; negative=0 tumor grade: matured=0; moderate=1; immature=2 Radiotherapy with or without chemotherapy after operation: performed =1; not performed =0 Recurrence/relapse: rec =1; not rec =0 suvival status:death=1; survive=0 smoking status (Pack year of smoking): none smoker=0; pack-year <20 = 1 (moderate smoker); pack-year <=20 = 2 (heavy smoker) alcohol drinking: Alcohol drinkers were divided into non-drinker or less than one drink per day =0: one and more but less than two drinks per day = moderate drinker 1: two and more drinks per day=heavy drinker 2: during the 20 years preceding their treatment for HNSCC. One drink was defined as containing approximately 10g of alcohol, which is considered equal to 30 ml of hard liquor, 100 ml of wine containing 12% alcohol, or 360 ml of beer.

Dataset Information

Distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma.

Publications

Distinct effects of alcohol consumption and smoking on genetic alterations in head and neck carcinoma.

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