Alcohol Dehydrogenase 3 and Risk of Squamous Cell Carcinomas of the Head and Neck

Abstract

In order to examine the association between alcohol dehydrogenase 3 (ADH3) genotypes and risk of head and neck squamous cell carcinomas (HNSCC), we conducted a hospital based case-control study including 348 cases and 330 controls. DNA isolated from exfoliated cells from the oral cavity were genotyped for ADH3 polymorphisms using PCR followed by SspI digestion. Odds ratios (OR) and hazards ratios (HR) were done by unconditional logistic regression and Cox regression. Relative to ADH3 2-2 carriers, ADH3 1-1 [OR, 0.7; 95% confidence interval (CI), 0.4-1.1] and ADH3 1-2 (OR, 0.8; 95% CI, 0.5-1.2) had a nonsignificant reduced risk of HNSCC. ADH 1-2 smokers of >30 pack-years were at decreased risk of oral cavity squamous cell carcinomas compared with ADH3 2-2 (OR, 0.3, 0.1-0.9), whereas ADH3 1-1 smokers were not. After adjustment, those with ADH3 1-2 had significantly worse overall survival compared with ADH3 1-1 (HR, 0.3, 0.2-0.6) or ADH3 2-2 (HR, 0.4, 0.2-0.9) and increased recurrence (ADH3 1-1 , 0.2, 0.1-0.6; ADH3 2-2 , 0.6, 0.2-1.3). Our data did not show that ADH3 genotypes had a significantly independent effect on the risk of HNSCC, nor did they modify the risks increased by alcohol or tobacco consumption and high-risk human papillomavirus infection. However, participants with ADH3 1-2 genotype were associated with poorer survival compared with those who had the other two ADH3 genotypes and a higher rate of recurrence than participants with ADH3 1-1 genotype. (Cancer Epidemiol Biomarkers Prev 2005;14(3):626 -32)

Evidence for an Important Role of Alcohol- and Aldehyde-Metabolizing Genes in Cancers of the Upper Aerodigestive Tract

“…In a pooled analysis of seven published case-control studies, including 1,325 cases and 1,760 controls, no increased risk of head and neck cancer for the ADH1C valine homozygote at codon 350 or heterozygote genotypes were observed (7). Subsequent published studies on the ADH1C genotype have mostly reported null results, with studies in Brazil (18) and Iowa (19) reporting no overall association with head and neck cancer, and a study in Japan reporting no association with esophageal cancer (17). Peters et al (20) reported an increased risk of laryngeal cancer for carrying the ADH1C Val 350 allele, although no increase in overall head and neck cancer risk was observed.…”

Clinical features and prognostic factors in patients with head and neck cancer: Results from a multicentric study

“…The 5-year survival rate after SPC diagnosis is about 8% if the malignancy is outside the head and neck area, and increased to 30% if the SPC is an HNC [25]. So far, few studies examined the prognostic significance of gene polymorphisms in alcohol metabolism and oxidative stress-related genes in patients with HNC, and they reported evidence of an association of specific polymorphisms with survival (CYP2E1, ADH3) or higher recurrence (CYP1A2) [14,15,26]. The purpose of our study is to evaluate whether two specific alcohol dehydrogenase genes [ADH1B (rs1229984) and ADH7 (rs1573496)], and established demographics and lifestyle-related risk factors for HNC, influence overall survival, recurrence, and development of SPC in HNC patients.…”

DNA Methyltransferase and Alcohol Dehydrogenase: Gene-Nutrient Interactions in Relation to Risk of Colorectal Polyps

“…The ADH1C wild-type allele (ADH1C *1) oxidizes ethanol 2.5 times faster than those encoded by the ADH1C variant allele (38). Because of this, it has been hypothesized that fast metabolizers (homozygous for the fast allele of ADH1C ) of ethanol would have higher levels of acetaldehyde per gram of tissue in the colonic mucosa compared with all other tissues and would therefore be at greater risk for colorectal cancer (36).…”