Glutathione S-transferase polymorphisms and risk of second primary malignancy after index squamous cell carcinoma of the head and neck.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zafereo, ME; Sturgis, EM; Aleem, S; Chaung, K; Wei, Q; Li, G

Published Date

  • May 2009

Published In

Volume / Issue

  • 2 / 5

Start / End Page

  • 432 - 439

PubMed ID

  • 19401526

Pubmed Central ID

  • PMC2698715

Electronic International Standard Serial Number (EISSN)

  • 1940-6215

Digital Object Identifier (DOI)

  • 10.1158/1940-6207.CAPR-08-0222


  • eng

Conference Location

  • United States