Laryngeal cancer risk in Caucasians is associated with alcohol and tobacco consumption but not modified by genetic polymorphisms in class I alcohol dehydrogenases ADH1B and ADH1C, and glutathione-S-transferases GSTM1 and GSTT1.
OBJECTIVE
Alcohol and tobacco consumption are recognized risk factors for upper aerodigestive tract tumours, however individual susceptibility to these environmental factors varies. As part of the Rhein-Neckar Larynx-case-control study, this study investigated the potential risk-modifying effect of genetic polymorphisms in enzymes involved in ethanol and tobacco carcinogen metabolism for laryngeal cancer in Germany.


METHODS
Two hundred and forty-five cases and 251 population-based controls, matched by age and gender, were genotyped for genetic polymorphisms in ADH1B, ADH1C, GSTM1 and GSTT1, using genomic DNA isolated from peripheral lymphocytes and employing PCR and PCR/restriction fragment length polymorphism-based methods.


RESULTS
Neither the putative risk genotypes ADH1B*2/*1 (OR 0.86, 95% confidence interval (CI): 0.41-1.82) or ADH1C*1/*1 (OR 1.06, CI 0.7-1.62) nor GSTM1 null (OR 0.94, CI 0.62-1.42) or GSTT1 null (OR 1.34, CI 0.74-2.42) were associated with an overall increased risk for laryngeal cancer. Stratified analyses were carried out to determine the gene-environment interaction in relation to laryngeal cancer risk. However, ADH1B or ADH1C genotypes did not markedly modify the risk observed after stratification by alcohol consumption, and stratification by cumulative smoking exposure (in packyears) did not show an association of GSTM1 or GSTT1 genotype with laryngeal carcinoma either.


CONCLUSIONS
The lack of risk modification by the studied genotypes emphasizes the importance of environmental exposure to tobacco smoke and alcohol as major risk factors for laryngeal cancer in the German study population.
Risch
Angela
A
Division of Toxicology and Cancer Risk Factors German Cancer Research Center (DKFZ), Heidelberg, Germany. a.risch@dkfz.de
Ramroth
Heribert
H
Raedts
Vivianne
V
Rajaee-Behbahani
Nahid
N
Schmezer
Peter
P
Bartsch
Helmut
H
Becher
Heiko
H
Dietz
Andreas
A
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005838:Genotype; D005858:Germany; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012907:Smoking / Q000009:adverse effects*; D044465:White People / Q000235:genetics*
D000426:Alcohol Dehydrogenase; D004247:DNA; D004273:DNA, Neoplasm; D005982:Glutathione Transferase; C489332:ADH1B protein, human; C420272:ADH1C protein, human; C413545:glutathione S-transferase T1