Gene Environment Interaction in Head and Neck Cancer

Summary

Principal Investigator: Andrew Olshan
Abstract: DESCRIPTION: The major goal of the proposed study is to comprehensively evaluate the role of genetic susceptibility in the etiology of squamous cell carcinoma of the head and neck (SCCHN; including oral cavity, pharynx, and larynx). SCCHN provides an ideal model for the investigation of gene-environment interaction in cancer given its strong and highly prevalent risk factors, tobacco and alcohol. Polymorphisms in genes representing metabolism (activation and detoxification) of carcinogens, mediators of oxidative stress, and DNA repair may help to clarify dose-response relationships needed for risk assessment, elucidate low dose exposure effects, pinpoint specific carcinogens that act as part of complex mixtures, and to identify susceptible subgroups of individuals most likely to benefit from interventions to reduce exposure. The proposed North Carolina population-based case-control study including 1,700 cases and 1,700 controls will have the ability to more precisely define the nature of the gene-environment interactions related to the risk of SCCHN. This will be the largest study of head and neck cancer ever conducted in the United States. North Carolina is an excellent setting to conduct such a study given the large biracial population, relatively high prevalence of tobacco use, and the research team's experience with conducting population-based molecular epidemiologic studies of cancer. The previous gene-environment studies have yielded generally inconsistent results with respect to several metabolizing enzyme polymorphisms. These studies have been limited by their relatively small size (typically fewer than 200 cases), hospital-based design and examination of a small number of enzymes. The size and population-based design should allow us to more confidently confirm or reject associations raised in previous studies. Finally, the study size will permit us to consider selected gene-gene exposure interactions and examine important subgroups defined by age, gender, race, and tumor site. The systematic collection of tumor blocks will also facilitate future studies of "downstream" somatic alterations of tumor suppressor genes and oncogenes. The proposed study should contribute knowledge on gene-environment interactions for cancer of the head and neck, but also for other tobacco- and alcohol-related cancers and possibly cancers of unknown etiology.
Funding Period: 2001-07-18 - 2008-06-30
more information: NIH RePORT

Top Publications

  1. pmc Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival
    Annah B Wyss
    Department of Epidemiology, Gillings School of Global Pubic Health, University of North Carolina at Chapel Hill, 2101B McGavran Greenberg Hall, CB 7435, Chapel Hill, NC, 27599, USA
    Cancer Causes Control 25:437-50. 2014
  2. pmc Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium
    Morgan A Marks
    Authors Affiliations Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville Johns Hopkins School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Community Health, School of Medicine, Brown University, Providence, Rhode Island International Agency of Research on Cancer Hospices Civils de Lyon, Pole Information Medicale Evaluation Recherche Universite Lyon 1, Equipe d Accueil 4129 International Prevention Research Institute, Lyon, France Fred Hutchinson Cancer Research Cancer, Seattle, Washington University of Iowa College of Public Health, Iowa City, Iowa School of Public Health, University of North Carolina, Chapel Hill, North Carolina Department of Head and Neck Surgery and Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas UCLA School of Public Health, Los Angeles, California Departments of Epidemiology and Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan Penn State College of Medicine, Hershey, Pennsylvania Boston University School of Public Health, Boston, Massachusetts Faculdade de Saude Publica, Universidade de Sao Paulo, Sao Paulo Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro Universidade Federal de Pelotas, Pelotas Hospital de Clinicas de Porto Alegre, Port Alegre, Brazil Institute Oncology Angel H Roffo, University of Buenos Aires, Buenos Aires, Brazil
    Cancer Epidemiol Biomarkers Prev 23:160-71. 2014
  3. pmc Body mass index and risk of head and neck cancer by race: the Carolina Head and Neck Cancer Epidemiology Study
    Jessica L Petrick
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC Electronic address
    Ann Epidemiol 24:160-164.e1. 2014
  4. pmc Single-nucleotide polymorphisms in nucleotide excision repair genes, cigarette smoking, and the risk of head and neck cancer
    Annah B Wyss
    Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina 27599, USA
    Cancer Epidemiol Biomarkers Prev 22:1428-45. 2013
  5. pmc Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer
    Anne M Hakenewerth
    Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cancer Epidemiol 37:479-91. 2013
  6. pmc Racial differences in the relationship between tobacco, alcohol, and squamous cell carcinoma of the head and neck
    Jeanette A Stingone
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 7435, USA
    Cancer Causes Control 24:649-64. 2013
  7. pmc Associations between dietary patterns and head and neck cancer: the Carolina head and neck cancer epidemiology study
    Patrick T Bradshaw
    Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA
    Am J Epidemiol 175:1225-33. 2012
  8. pmc Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer
    Anne M Hakenewerth
    Department of Epidemiology, University of North Carolina at Chapel Hill, 100 Market Street, Chapel Hill, NC 27516, USA
    Cancer Epidemiol Biomarkers Prev 20:2438-49. 2011
  9. pmc High XRCC1 protein expression is associated with poorer survival in patients with head and neck squamous cell carcinoma
    Mei Kim Ang
    UNC Lineberger Comprehensive Cancer Center Department of Biostatistics, UNC School of Medicine, Chapel Hill, North Carolina, USA
    Clin Cancer Res 17:6542-52. 2011
  10. pmc Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study
    Kimon Divaris
    Department of Epidemiology, CB 7435, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 7435, USA
    Cancer Causes Control 21:567-75. 2010

Scientific Experts

  • Patricia V Basta
  • Andrew F Olshan
  • Mark C Weissler
  • William K Funkhouser
  • Annah B Wyss
  • Amy H Herring
  • Jill S Barnholtz-Sloan
  • Anne M Hakenewerth
  • Patrick T Bradshaw
  • Jessica L Petrick
  • Morgan A Marks
  • Christy L Avery
  • Jeannette T Bensen
  • Jeanette A Stingone
  • Ivan Rusyn
  • Robert C Millikan
  • Kari E North
  • Mary E Bell
  • Mei Kim Ang
  • Kimon Divaris
  • Leticia Fernandez
  • Joshua Muscat
  • Annah Wyss
  • Mia M Gaudet
  • Gypsyamber D'Souza
  • Qingyi Wei
  • Stephen M Schwartz
  • Paul Brennan
  • Philip Lazarus
  • Hal Morgenstern
  • MICHAEL MCCLEAN
  • Marshall Posner
  • Ana Menezes
  • Karl Kelsey
  • Erich M Sturgis
  • Elaine Smith
  • Elena Matos
  • Kurt Straif
  • Victor W√ľnsch-Filho
  • Zuo Feng Zhang
  • Yuan Chin Amy Lee
  • Anil K Chaturvedi
  • Thomas L Vaughan
  • Alexander W Daudt
  • Paolo Boffetta
  • Chu Chen
  • Julien Berthiller
  • Sergio Koifman
  • Maria Paula Curado
  • Mia Hashibe
  • Marci Campbell
  • Anna Maria Siega-Riz
  • D Neil Hayes
  • Liza Makowski
  • C Ryan Miller
  • Karen Fritchie
  • Marion E Couch
  • William F Funkhouser
  • Alex J Freemerman
  • Matthew D Wilkerson
  • Leigh B Thorne
  • Stephen L Harris
  • William W Shockley
  • Carol G Shores
  • Xiao Ying Yin
  • Mihir R Patel
  • Ni Zhao
  • Vonn Walter
  • Trevor Hackman
  • Michele C Hayward
  • Adam M Zanation
  • Sneha Sundaram
  • Bhishamjit S Chera
  • Yufeng Liu
  • Joanna Smith

Detail Information

Publications11

  1. pmc Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival
    Annah B Wyss
    Department of Epidemiology, Gillings School of Global Pubic Health, University of North Carolina at Chapel Hill, 2101B McGavran Greenberg Hall, CB 7435, Chapel Hill, NC, 27599, USA
    Cancer Causes Control 25:437-50. 2014
    ..Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment...
  2. pmc Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium
    Morgan A Marks
    Authors Affiliations Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville Johns Hopkins School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Community Health, School of Medicine, Brown University, Providence, Rhode Island International Agency of Research on Cancer Hospices Civils de Lyon, Pole Information Medicale Evaluation Recherche Universite Lyon 1, Equipe d Accueil 4129 International Prevention Research Institute, Lyon, France Fred Hutchinson Cancer Research Cancer, Seattle, Washington University of Iowa College of Public Health, Iowa City, Iowa School of Public Health, University of North Carolina, Chapel Hill, North Carolina Department of Head and Neck Surgery and Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas UCLA School of Public Health, Los Angeles, California Departments of Epidemiology and Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan Penn State College of Medicine, Hershey, Pennsylvania Boston University School of Public Health, Boston, Massachusetts Faculdade de Saude Publica, Universidade de Sao Paulo, Sao Paulo Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro Universidade Federal de Pelotas, Pelotas Hospital de Clinicas de Porto Alegre, Port Alegre, Brazil Institute Oncology Angel H Roffo, University of Buenos Aires, Buenos Aires, Brazil
    Cancer Epidemiol Biomarkers Prev 23:160-71. 2014
    ..The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950...
  3. pmc Body mass index and risk of head and neck cancer by race: the Carolina Head and Neck Cancer Epidemiology Study
    Jessica L Petrick
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC Electronic address
    Ann Epidemiol 24:160-164.e1. 2014
    ..5 kg/m(2)) and decreased for overweight or obesity (25.0 to <30.0 and >30 kg/m(2), respectively), compared with normal weight (18.5 to <25.0 kg/m(2))...
  4. pmc Single-nucleotide polymorphisms in nucleotide excision repair genes, cigarette smoking, and the risk of head and neck cancer
    Annah B Wyss
    Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina 27599, USA
    Cancer Epidemiol Biomarkers Prev 22:1428-45. 2013
    ..Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC...
  5. pmc Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer
    Anne M Hakenewerth
    Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cancer Epidemiol 37:479-91. 2013
    ..We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival...
  6. pmc Racial differences in the relationship between tobacco, alcohol, and squamous cell carcinoma of the head and neck
    Jeanette A Stingone
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 7435, USA
    Cancer Causes Control 24:649-64. 2013
    ..The Carolina Head and Neck Cancer Study, a population-based case-control study, was utilized to determine whether relationships between tobacco and alcohol use and SCCHN differed by race...
  7. pmc Associations between dietary patterns and head and neck cancer: the Carolina head and neck cancer epidemiology study
    Patrick T Bradshaw
    Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA
    Am J Epidemiol 175:1225-33. 2012
    ..12, 95% confidence interval: 1.21, 3.72). These findings underline the importance of a dietary pattern rich in fruits and vegetables and low in high-fat and processed meats and sweets for prevention of head and neck cancer...
  8. pmc Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer
    Anne M Hakenewerth
    Department of Epidemiology, University of North Carolina at Chapel Hill, 100 Market Street, Chapel Hill, NC 27516, USA
    Cancer Epidemiol Biomarkers Prev 20:2438-49. 2011
    ..Genetic variation in the oxidative stress pathway may impact the carcinogenic effect of reactive oxygen species produced by ethanol metabolism. We hypothesized that alcohol interacts with these pathways to affect SCCHN incidence...
  9. pmc High XRCC1 protein expression is associated with poorer survival in patients with head and neck squamous cell carcinoma
    Mei Kim Ang
    UNC Lineberger Comprehensive Cancer Center Department of Biostatistics, UNC School of Medicine, Chapel Hill, North Carolina, USA
    Clin Cancer Res 17:6542-52. 2011
    ..We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome...
  10. pmc Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study
    Kimon Divaris
    Department of Epidemiology, CB 7435, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 7435, USA
    Cancer Causes Control 21:567-75. 2010
    ..Thus far, evidence has been inconclusive; our objective was to study the association between oral health and SCCHN risk in the context of a large population-based study...
  11. pmc Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck
    Patricia V Basta
    Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7435, USA
    Cancer Detect Prev 32:200-8. 2008
    ..Here we present data examining the association of genetic variation in one of the key enzymes of the PPP, Transaldolase 1 (TALDO1) with squamous cell carcinoma of the head and neck (SCCHN)...