Association of cytochrome P450 2E1 polymorphisms and head and neck squamous cell cancer.
The development of head and neck squamous cell cancer (HNSCC) is known to be strongly associated with tobacco use. One of the main enzymes for bioactivation of tobacco-related substances is the cytochrome 450 (CYP)2E1, of which different genetic variants are described. Analyzing a correlation between certain neoplasia and alteration of the CYP2E1 gene, most studies focus on the polymorphisms -1053C>T and 7632T>A, but recently another polymorphism, named -71G>T, with enhanced transcriptional activity, has been identified. In the current case-control study we investigate the putative association of the mentioned CYP2E1 polymorphisms on the risk of HNSCC. Comparing 312 German individuals with HNSCC to 299 controls we found a significantly enhanced risk for the development of that neoplasia in smoking carriers of -71G>T heterozygosity, while in -1053C>T and 7632T>A polymorphisms a corresponding correlation was absent. Since a coincidence of an aberrant p53 gene and CYP2E1 mutations has been described, we choose a subgroup of 140 patients with HNSCC for analyzing an association of mutations in these two genes. However, no such association could be found in either of the mentioned polymorphisms. Further studies have to focus on the -71G>T polymorphism and its possible linkage to cancers, in which smoking is a known risk-factor, as well as its functional relevance concerning the bioactivation of tobacco-related substances.
Neuhaus
Thomas
T
Medizinische Universitäts-Poliklinik Bonn, Universität Bonn, Wilhelmstr. 35-37, D-53111 Bonn, Germany.
Ko
Yon-Dschun
YD
Lorenzen
Katrin
K
Fronhoffs
Stefan
S
Harth
Volker
V
Bröde
Peter
P
Vetter
Hans
H
Bolt
Hermann M
HM
Pesch
Beate
B
Brüning
Thomas
T
D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000737:chemistry / Q000235:genetics*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000235:genetics / Q000378:metabolism
D004273:DNA, Neoplasm; D019392:Cytochrome P-450 CYP2E1