title: Glutathione S-transferase polymorphisms and risk of second primary malignancy after index squamous cell carcinoma of the head and neck.
abstract: Glutathione S-transferases (GST) detoxify carcinogens in tobacco smoke, which plays a major role in development of not only squamous cell carcinoma of the head and neck (SCCHN) but also second primary malignancy (SPM) after index SCCHN. We hypothesized that GSTM1 null, GSTT1 null, GSTP1 Ile(105)Val, and GSTP1 Ala(114)Val polymorphisms would individually and, more likely, collectively show an association with risk of SPM after index SCCHN. One thousand three hundred seventy-six incident SCCHN patients were prospectively recruited between May 1996 and December 2006, genotyped, and followed for SPM development. One hundred ten patients (8%) developed SPM: 43 (39%) second SCCHN, 38 (35%) other tobacco-associated sites, and 29 (26%) other non-tobacco-associated sites. Patients with GSTP1 Ile(105)Val polymorphism had a statistically significant association with risk of SPM development (adjusted hazard ratio, 1.7; 95% confidence interval, 1.1-2.5). However, no statistically significant associations were observed with GSTM1, GSTT1, or GSTP1 Ala(114)Val polymorphisms. After combining risk genotypes for all four polymorphisms, rates of SPM development with 0 to 1, 2, 3, and 4 risk genotypes were 6.4%, 8.4%, 10.9%, and 15.1%, respectively, and a stepwise increase in SPM risk was observed with increasing number of risk genotypes (P = 0.004 for trend). Patients with 3 to 4 risk genotypes had a 1.7-fold increased risk for SPM compared with patients with 0 to 2 risk genotypes (hazard ratio, 1.70; 95% confidence interval, 1.2-2.5). This large prospective cohort study supports a modestly increased risk of SPM after index SCCHN with GSTP1 Ile(105)Val polymorphism and an even greater risk of SPM with multiple combined GST risk genotypes.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Zafereo
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Sal
authors.initials: S
authors.lastname: Aleem
authors.forename: Katrina
authors.initials: K
authors.lastname: Chaung
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D005982:Glutathione Transferase