Genome-Wide Analysis of Head and Neck Squamous Cell Carcinomas Reveals HPV, TP53, Smoking and Alcohol-Related Allele-Based Acquired Uniparental Disomy Genomic Alterations

Musaffe Tuna, Christopher I. Amos, Gordon Mills

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    1 Citation (Scopus)

    Abstract

    Smoking and alcohol intake are major risk factors in head and neck squamous cell carcinomas (HNSCCs). Although the link between TP53 mutation and smoking has been well established, very little is known about the link between acquired uniparental disomy (aUPD) and smoking and/or alcohol consumption or other clinical characteristics. We used TCGA genomic data to investigate whether smoking, alcohol intake, clinical and demographic variables, HPV status and TP53 mutation are associated with aUPD at specific chromosomal regions. In multivariate analysis, we found association between aUPD regions and risk factors and clinical variables of disease. aUPD regions on chromosome 4q, 5q, 9p, 9q, 13q, 17p and CDKN2A occurred significantly more often in patients with TP53-mutated HNSCC than in those with wild-type HNSCC, while aUPD regions on chromosome 9p and at CDKN2A were significantly more frequent in females than in males. Besides, aUPD occurred more frequent in HPV-positive than in HPV-negative samples with all HNSCC and larynx cancers on chromosome 9q 15q and 17p. Moreover, aUPD on CDKN2A region occurred more often in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers, while aUPD region on chromosome 5q occurred less in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers. Similarly, aUPD region on chromosome 5q occurred less in smokers than nonsmokers in patients with all HNSCC and oral cavity cancers. In conclusion, aUPD regions are not random, and certain regions are associated with risk factors for disease, and with TP53 mutation status.

    Original languageEnglish (US)
    Pages (from-to)197-205
    Number of pages9
    JournalNeoplasia (United States)
    Volume21
    Issue number2
    DOIs
    StatePublished - Feb 1 2019

    Fingerprint

    Uniparental Disomy
    Smoking
    Alleles
    Alcohols
    Genome
    Chromosomes
    Mouth Neoplasms
    Mouth
    Mutation
    Carcinoma, squamous cell of head and neck
    Squamous Cell Neoplasms
    Laryngeal Neoplasms
    Head and Neck Neoplasms
    Alcohol Drinking
    Multivariate Analysis
    Demography

    ASJC Scopus subject areas

    • Cancer Research

    Cite this

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    title = "Genome-Wide Analysis of Head and Neck Squamous Cell Carcinomas Reveals HPV, TP53, Smoking and Alcohol-Related Allele-Based Acquired Uniparental Disomy Genomic Alterations",
    abstract = "Smoking and alcohol intake are major risk factors in head and neck squamous cell carcinomas (HNSCCs). Although the link between TP53 mutation and smoking has been well established, very little is known about the link between acquired uniparental disomy (aUPD) and smoking and/or alcohol consumption or other clinical characteristics. We used TCGA genomic data to investigate whether smoking, alcohol intake, clinical and demographic variables, HPV status and TP53 mutation are associated with aUPD at specific chromosomal regions. In multivariate analysis, we found association between aUPD regions and risk factors and clinical variables of disease. aUPD regions on chromosome 4q, 5q, 9p, 9q, 13q, 17p and CDKN2A occurred significantly more often in patients with TP53-mutated HNSCC than in those with wild-type HNSCC, while aUPD regions on chromosome 9p and at CDKN2A were significantly more frequent in females than in males. Besides, aUPD occurred more frequent in HPV-positive than in HPV-negative samples with all HNSCC and larynx cancers on chromosome 9q 15q and 17p. Moreover, aUPD on CDKN2A region occurred more often in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers, while aUPD region on chromosome 5q occurred less in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers. Similarly, aUPD region on chromosome 5q occurred less in smokers than nonsmokers in patients with all HNSCC and oral cavity cancers. In conclusion, aUPD regions are not random, and certain regions are associated with risk factors for disease, and with TP53 mutation status.",
    author = "Musaffe Tuna and Amos, {Christopher I.} and Gordon Mills",
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    AU - Amos, Christopher I.

    AU - Mills, Gordon

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    AB - Smoking and alcohol intake are major risk factors in head and neck squamous cell carcinomas (HNSCCs). Although the link between TP53 mutation and smoking has been well established, very little is known about the link between acquired uniparental disomy (aUPD) and smoking and/or alcohol consumption or other clinical characteristics. We used TCGA genomic data to investigate whether smoking, alcohol intake, clinical and demographic variables, HPV status and TP53 mutation are associated with aUPD at specific chromosomal regions. In multivariate analysis, we found association between aUPD regions and risk factors and clinical variables of disease. aUPD regions on chromosome 4q, 5q, 9p, 9q, 13q, 17p and CDKN2A occurred significantly more often in patients with TP53-mutated HNSCC than in those with wild-type HNSCC, while aUPD regions on chromosome 9p and at CDKN2A were significantly more frequent in females than in males. Besides, aUPD occurred more frequent in HPV-positive than in HPV-negative samples with all HNSCC and larynx cancers on chromosome 9q 15q and 17p. Moreover, aUPD on CDKN2A region occurred more often in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers, while aUPD region on chromosome 5q occurred less in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers. Similarly, aUPD region on chromosome 5q occurred less in smokers than nonsmokers in patients with all HNSCC and oral cavity cancers. In conclusion, aUPD regions are not random, and certain regions are associated with risk factors for disease, and with TP53 mutation status.

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