title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
authors.forename: Takanori
authors.initials: T
authors.lastname: Hama
authors.forename: Toshihito
authors.initials: T
authors.lastname: Suda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
authors.forename: Chikako
authors.initials: C
authors.lastname: Sakanashi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Akutsu
authors.forename: Suguru
authors.initials: S
authors.lastname: Amagaya
authors.forename: Kazuhumi
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Yu
authors.initials: Y
authors.lastname: Imai
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Mezawa
authors.forename: Miki
authors.initials: M
authors.lastname: Noya
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.forename: Aki
authors.initials: A
authors.lastname: Mafune
authors.forename: Takakuni
authors.initials: T
authors.lastname: Kato
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kojima
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D002877:Chromosomes, Human / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics; D012907:Smoking / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53