Evaluation of glutathione S‐transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early‐stage head and neck cancer

Minard, Charles G.; Spitz, Margaret R.; Wu, Xifeng; Hong, Waun Ki; Etzel, Carol J.

doi:10.1002/cncr.21928

Cited by 29 publications

(22 citation statements)

References 47 publications

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“…Exposure to environmental caricinogens and genetic variation in response to this exposure have been linked to both SCCHN and SPM (7, 16, 17). As phase II detoxifying enzymes, the glutathione S-transferases have been targeted as possible genetic biomarkers to predict malignancy risk.…”

Section: Discussionmentioning

confidence: 99%

“…Matthias and others found a significantly higher rate of the GSTT1 null genotype in 39 patients with multiple SCCHN compared to patients with a single SCCHN, but did not find significant differences associated with the GSTM1 null genotype or the GSTP1 Ile105Val polymorphism (19). Minard et al reported 50 SPMs in a cohort of 303 patients with early stage disease, with an increased risk of SPM associated with the GSTM1 null genotype, but not the GSTT1 null genotype (17). …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Glutathione S-Transferase Polymorphisms and Risk of Second Primary Malignancy after Index Squamous Cell Carcinoma of the Head and Neck

Zafereo

Aleem

Chaung

et al. 2009

Cancer Prevention Research

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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.Approximately 80% to 90% of squamous cell carcinoma of the head and neck (SCCHN) in the United States has historically been attributed to tobacco and alcohol (1). Cigarette smokers are estimated to be at a 10-fold increased risk over never smokers of developing SCCHN, and alcohol has been suggested both to be an independent risk factor for SCCHN and to enhance the risk associated with smoking (2). However, most smokers and drinkers never develop SCCHN, suggesting that genetic susceptibility also contributes to SCCHN etiology. Surgery, radiotherapy, and chemotherapy cure many SCCHN, but a significant cause of posttreatment morbidity and mortality is the development of second primary malignancies (SPM), estimated to occur in ∼15% of SCCHN patients (3).Enzymes in carcinogen detoxification, nucleotide excision repair, cell cycle control, and apoptosis pathways have all been suggested to interact with tobacco-associated carcinogens to modulate interindividual susceptibility to SCCHN (4, 5). Glutathione S-transferases (GST) are a family of seven phase II metabolizing enzymes that play a central role in catalyzing the conjugation of electrophilic compounds such as environmental carcinogens to glutathione, converting them to hydrophilic compounds that are less reactive and more easily excreted (6). Th...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glutathione S-Transferase Polymorphisms and Risk of Second Primary Malignancy after Index Squamous Cell Carcinoma of the Head and Neck

Zafereo

Aleem

Chaung

et al. 2009

Cancer Prevention Research

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“…GST polymorphisms may be prognostic in cancers of the prostate (94) and lung (95) cancer and non-Hodgkin's lymphoma (96). Four studies found conflicting results between the GST polymorphisms and HNC outcomes (24,44,92,97).…”

Section: Resultsmentioning

confidence: 99%

“…New methodologies and more accurate measurements of dose delivery may promote future toxicity studies. It was also promising to see some studies evaluate specific subsets of uniformly-treated patients, such as Stage I and II patients treated with radiation (70,97), or HNC patients treated with surgery (24,78,79,88,89,103), in addition to performing multivariate analyses to adjust for additional prognostic factors. This reflects a shift towards better understanding of the impact of clinical prognostic factors on outcome as well as how prognostic factors in general are utilized in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms and Head and Neck Cancer Outcomes: A Review

Hopkins

Cescon

Tse

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Head and neck cancer (HNC) patients have variable prognoses even within the same clinical stage and while receiving similar treatments. The number of studies of genetic polymorphisms as prognostic factors of HNC outcomes is growing. Candidate polymorphisms have been evaluated in DNA repair, cell cycle, xenobiotic metabolism, and growth factor pathways. Polymorphisms of XRCC1, FGFR, and CCND1 have been consistently associated with HNC survival in at least two studies, whereas most of the other polymorphisms have either conflicting data or were from single studies. Heterogeneity and lack of description of patient populations and lack of accounting for multiple comparisons were common problems in a significant proportion of studies. Despite a large number of exploratory studies, large replication studies in wellcharacterized HNC populations are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(3):490 -9)

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“…Its effect was essentially "washed-out" by the difference in the placebo and 13-cRA arms. This wash-out likely also occurred in 3 other unstratified/combined-arm studies focusing on SPT/recurrence prognostic factors by the same group of investigators in the phase-III 13-cRA trial (22)(23)(24). In the past, investigators have tended to combine arms for genotyping studies of negative/neutral trials.…”

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confidence: 93%

A Strong Case for Personalized, Targeted Cancer Prevention

Dawson

2011

Cancer Prevention Research

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The study reported by Lee and colleagues in this issue of the journal (beginning on page 185) incorporated global genetic variation within a new assessment of the outcome of a previously reported phase-III trial of low-dose 13-cis-retinoic acid (13-cRA) for preventing second primary tumors (SPT) or the recurrence of head-and-neck cancer. This analysis identified genotypes of common single-nucleotide polymorphisms (SNP) and cumulative effect and potential gene-gene interactions that were highly associated with increased placebo-arm risk (prognostic) and/or with reduced treatment-arm risk and longer event-free survival (predictive). For example, the wild-type rs3118570 SNP of the retinoid X receptor alpha gene (carried by 71% of the 13-cRA trial population) marked a 3.33-fold increased SPT/recurrence risk in the placebo arm and a 38% reduced risk in the treatment arm. Adding two other informative genotypes strengthened the treatment-arm risk reduction to 76%, although the genotype trio reflected only 13% of the trial population. This report extends the concept of personalized therapy to cancer prevention.Cancer Prev Res; 4(2); 173-6. Ó2011 AACR.

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Evaluation of glutathione S‐transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early‐stage head and neck cancer

Cited by 29 publications

References 47 publications

Glutathione S-Transferase Polymorphisms and Risk of Second Primary Malignancy after Index Squamous Cell Carcinoma of the Head and Neck

Glutathione S-Transferase Polymorphisms and Risk of Second Primary Malignancy after Index Squamous Cell Carcinoma of the Head and Neck

Genetic Polymorphisms and Head and Neck Cancer Outcomes: A Review

A Strong Case for Personalized, Targeted Cancer Prevention

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