Centers for Disease Control and Prevention
Centers for Disease Control and Prevention		 Centers for Disease Control and Prevention CDC Home Search CDC CDC Health Topics A-Z    
Office of Genomics and Disease Prevention  
Office of Genomics and Disease Prevention
 
chromosome fact sheet
GSTM1, GSTT1, and the Risk of Squamous Cell Carcinoma of the Head and Neck
 Stacy A. Geisler & Andrew F. Olshan
print version
HuGE review

Published August 9th, 2001
 
chromosome   Gene GSTM1: Polymorphism of this gene results in either production of an
chromosome enzyme known to play a role in Phase II detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke or no production of enzyme (deletion  polymorphism).  This gene has been mapped to
chromosome 1p13.3.

GSTT1: Polymorphism of this gene results either in production of an enzyme known to activate ethylene oxide, epoxybutanes, halomethanes, and methyle bromide or no production of enzyme (deletion polymorphism). It is also involved in Phase II detoxification of polyaromatic hydrocarbons (PAHs) found in tobacco smoke (considered as a minor pathway). This gene has been mapped to chromosome 22q11.2.
 

 Prevalence of Gene Variants

 GSTM1: In the United States, case-control studies have reported the deletion genotype varying from 23%-41% for those of African descent; 32%-53% for those of Asian descent, 40%-53% for those of Hispanic descent, and 35%-62% for those of European descent. Several population studies have reported the deletion polymorphism among U.S. Caucasians as ranging from 48%-57%. Other countries have reported varying frequencies of the deletion polymorphism. South American case-control (nonpopulation-based) studies have reported frequencies of 21% for Chileans and 55% for Caucasian Brazilians, 33% for black Brazilians, and 20% for Amazonian Brazilians.  Among the French, 46% have been reported to carry the deletion genotype. A large cross-sectional study conducted among Italians reported a frequency of 53%; two studies conducted in Hungary and the Slovak Republic measured frequencies of 44% and 50%, respectively.  A population-based study conducted in Finland found a prevalence of 40% for the GSTM1 deletion genotype. Groups such as Pacific Islanders and Malasians have a reported frequency of 62%-100%. Other Asian populations have high-reported frequencies of the deletion genotype ranging from 48%-50% for Japanese and 35%-63% for Chinese. A population-based study conducted among Chinese reported a frequency of 51% for the GSTM1 deletion genotype. Two Korean case-control studies found frequencies of 53% and 56% for the GSTM1 deletion genotype (1)

GSTT1: Studies of GSTT1 demonstrate that in the United States, the deletion polymorphism of GSTT1 is less common than the GSTM1 deletion polymorphism. Among those of European ancestry, 15%-31% have no functional GSTT1 enzyme. African descendents have frequencies ranging from 22%-29% while those of Hispanic origin carry GSTT1 deletions of 10%-12%. European studies have reported that the GSTT1 deletion genotype was present among 21% of Italians and 28% of Slovakians. One South American study found that 19% of both Caucasian and black Brazilians had the deletion genotype compared to 11% of Amazonian Brazilians. Asians have the highest reported GSTT1 deletion genotype. One study reported 58% of Chinese and 38% of Malaysians have the GSTT1 null genotype; two case-control studies measured 42% and 46% among Koreans. However, a recent population-based study conducted among Chinese found a prevalence of 46% for the GSTT1 deletion genotype among their study subjects (1)
 
Disease Burden Worldwide, squamous cell carcinoma of the head and neck (SCCHN) represents the third most common cancer among men and the fourth most common among women. Tobacco smoking remains the most important risk factor for SCCHN, with 90% of oral cancers and 80% of larynx cancers attributed to this habit. Given the high prevalence of the GSTM1 and GSTT1 deletion polymorphisms, the population-attributable risk of disease is extremely high for those who have the deletion genotype and who engage in tobacco smoking. 
 Interactions

Twenty-four studies have been published evaluating GSTM1, GSTT1, and the risk of SCCHN. The main effect of the gene has been inconsistent, with most studies reporting weak to moderate results. Modest evidence of interaction has been shown with imprecise estimates of effect for risk of SCCHN and GSTM1 null genotype among studies that have measured dose and duration of tobacco exposure (2-4). For example, after adjustment for age and gender, Sato et al. calculated odds ratios (OR) of 3.1 (1.6, 5.9), 3.9 (1.6, 9.1), and 16.2 (4.3, 61.0) for risk of oral cancer for those with the GSTM1 deletion genotype and increasing lifetime cigarette dose (4)

Among those studies that have evaluated gene-environment interaction for the GSTT1 deletion genotype, Olshan et al. reported a suggestive interaction with smoking. For those with the GSTT1 deletion genotype and who had never smoked (never smokers), the risk of SCCHN was 2.7 (0.5, 12.9) compared to never smokers without the GSTT1 deletion genotype. Less-than-one-pack-per-day smokers had an OR of 3.7 (0.7, 19.4) while one-pack-per-day-or-greater smokers had an OR of 7.0 (2.2, 22.0) compared to never smokers without the GSTT1 deletion genotype (3).

 
Laboratory Tests Individuals with homozygous deletions of either the GSTM1 locus or the GSTT1 locus have no enzymatic functional activity of the respective enzyme. This has been confirmed by phenotype assays that have demonstrated 94% or greater concordance between phenotype and genotype.  Genotyping methods used in the studies reviewed were consistent with the standard techniques employed for PCR, PCR-restriction fragment length polymorphisms, and multiplex PCR.  Internal control primers were stated for all studies.

 
Population Testing No population testing has been conducted to date, and none are indicated.

 
References  

1.         Geisler S, Olshan A. GSTM1, GSTT1 and risk of head and neck cancer: a mini-HuGE review. American Journal of Epidemiology 2001;154:95-105.

2.         Park J, Muscat J, Kaur T, Schantz S, Stern J, Richie J, et al. Comparison of GSTM polymorphisms and risk for oral cancer between African Americans and Caucasians. Pharmacogenetics 2000;10:123-31.

3.         Olshan A, Weissler M, Watson M, Bell D. GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1 polymorphisms, tobacco use, and the risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev 2000;9:185-91.

4.         Sato M, Sato T, Izumo T, Amagasa T. Genetic Polymorphism of drug-metabolizing enzymes and susceptibility to oral cancer.  Carcinogenesis 1999,20:1927-31.

 

Web sites National Cancer Institute

GENE CARD for GSTM1
Rebhan, M., Chalifa-Caspi, V., Prilusky, J., Lancet, D.
GeneCards: encyclopedia for genes, proteins and diseases.
Weizmann Institute of Science, Bioinformatics Unit & Genome Center (Rehovot, Israel), 1997. GeneCard for GSTM1, Last Update: 8 Jun 2001

GENE CARD for GSTT1
Rebhan, M., Chalifa-Caspi, V., Prilusky, J., Lancet, D.
GeneCards: encyclopedia for genes, proteins and diseases.
Weizmann Institute of Science, Bioinformatics Unit & Genome Center (Rehovot, Israel), 1997. GeneCard for GSTT1, Last Update: 8 Jun 2001

 

 

chromosome
Last Updated January 13, 2004