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Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer.

Publication ,  Journal Article
Hakenewerth, AM; Millikan, RC; Rusyn, I; Herring, AH; North, KE; Barnholtz-Sloan, JS; Funkhouser, WF; Weissler, MC; Olshan, AF
Published in: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
November 2011

Single-nucleotide polymorphisms (SNP) in alcohol metabolism genes are associated with squamous cell carcinoma of the head and neck (SCCHN) and may influence cancer risk in conjunction with alcohol. 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.Interview and genotyping data for 64 SNPs were obtained from 2,552 European- and African-American subjects (1,227 cases and 1,325 controls) from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study of SCCHN conducted in North Carolina from 2002 to 2006. We estimated ORs and 95% confidence intervals (CI) for SNPs and haplotypes, adjusting for age, sex, race, and duration of cigarette smoking. P values were adjusted for multiple testing using Bonferroni correction.Two SNPs were associated with SCCHN risk: ADH1B rs1229984 A allele (OR = 0.7; 95% CI, 0.6-0.9) and ALDH2 rs2238151 C allele (OR = 1.2; 95% CI, 1.1-1.4). Three were associated with subsite tumors: ADH1B rs17028834 C allele (larynx, OR = 1.5; 95% CI, 1.1-2.0), SOD2 rs4342445 A allele (oral cavity, OR = 1.3; 95% CI, 1.1-1.6), and SOD2 rs5746134 T allele (hypopharynx, OR = 2.1; 95% CI, 1.2-3.7). Four SNPs in alcohol metabolism genes interacted additively with alcohol consumption: ALDH2 rs2238151, ADH1B rs1159918, ADH7 rs1154460, and CYP2E1 rs2249695. No alcohol interactions were found for oxidative stress SNPs.Previously unreported associations of SNPs in ALDH2, CYP2E1, GPX2, SOD1, and SOD2 with SCCHN and subsite tumors provide evidence that alterations in alcohol and oxidative stress pathways influence SCCHN carcinogenesis and warrant further investigation.

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Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

DOI

EISSN

1538-7755

ISSN

1055-9965

Publication Date

November 2011

Volume

20

Issue

11

Start / End Page

2438 / 2449

Related Subject Headings

  • Young Adult
  • Squamous Cell Carcinoma of Head and Neck
  • Polymorphism, Single Nucleotide
  • Polymorphism, Genetic
  • Oxidative Stress
  • North Carolina
  • Middle Aged
  • Male
  • Humans
  • Head and Neck Neoplasms
 

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Hakenewerth, A. M., Millikan, R. C., Rusyn, I., Herring, A. H., North, K. E., Barnholtz-Sloan, J. S., … Olshan, A. F. (2011). Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer. Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 20(11), 2438–2449. https://doi.org/10.1158/1055-9965.epi-11-0649
Hakenewerth, Anne M., Robert C. Millikan, Ivan Rusyn, Amy H. Herring, Kari E. North, Jill S. Barnholtz-Sloan, William F. Funkhouser, Mark C. Weissler, and Andrew F. Olshan. “Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer.Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 20, no. 11 (November 2011): 2438–49. https://doi.org/10.1158/1055-9965.epi-11-0649.
Hakenewerth AM, Millikan RC, Rusyn I, Herring AH, North KE, Barnholtz-Sloan JS, et al. Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2011 Nov;20(11):2438–49.
Hakenewerth, Anne M., et al. “Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer.Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, vol. 20, no. 11, Nov. 2011, pp. 2438–49. Epmc, doi:10.1158/1055-9965.epi-11-0649.
Hakenewerth AM, Millikan RC, Rusyn I, Herring AH, North KE, Barnholtz-Sloan JS, Funkhouser WF, Weissler MC, Olshan AF. Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2011 Nov;20(11):2438–2449.

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

DOI

EISSN

1538-7755

ISSN

1055-9965

Publication Date

November 2011

Volume

20

Issue

11

Start / End Page

2438 / 2449

Related Subject Headings

  • Young Adult
  • Squamous Cell Carcinoma of Head and Neck
  • Polymorphism, Single Nucleotide
  • Polymorphism, Genetic
  • Oxidative Stress
  • North Carolina
  • Middle Aged
  • Male
  • Humans
  • Head and Neck Neoplasms