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Study of the Involvement of GSTP1 and Deregulation of the Fanconi Anemia Genes

Steve Tremblay, DMD, MSc; Patricia Pintor dos Reis, PhD; Grace Bradley, DMD, MSc; Natalie Naranjo Galloni, MD; Bayardo Perez-Ordonez, MD; Jeremy Freeman, MD; Dale Brown, MD; Ralph Gilbert, MD; Patrick Gullane, MD; Jonathan Irish, MD; Suzanne Kamel-Reid, PhD

Arch Otolaryngol Head Neck Surg. 2006;132:958-966.

Objective  To investigate whether oral squamous cell carcinomas (OSCCs) from young (40 years) and older (60 years) patients have differential expression levels of GSTP1, FANCA, FANCC, FANCD2, and FANCG.

Design  Quantitative real-time reverse transcriptase–polymerase chain reaction and immunohistochemical analysis were used to assess gene and protein expression, respectively.

Setting  This study was performed in a research institute within a hospital setting.

Patients  Our study group consisted of 104 patients (42 young and 62 older). We collected RNA from 32 OSCC samples (10 young and 22 older patients) for gene expression analysis. Seventy-seven OSCC samples (37 from young and 40 from older patients) were used for protein expression analysis. Five patients were studied in both analyses.

Results  Lower expression of GSTP1 (P = .04) and FANCA (P = .01) was observed in the tumors of young compared with older patients. We also detected lower expression of GSTP1 in the tumors of young patients compared with their nondysplastic mucosa (P = .01). FANCA was underexpressed in nondysplastic mucosa of young compared with older patients (P = .01). GSTP1 protein showed negative or low expression in 41% (n = 15 of 37) of young vs 5% (n = 2 of 40) of older patient tumors (P = .001). FANCG protein expression was absent or low in 81% (n = 30 of 37) of young compared with 36% (n = 15 of 40) of older patient tumors (P<.001).

Conclusions  Differences in expression levels of GSTP1, FANCA, and FANCG in OSCC of young and older patients suggest that different mechanisms may be involved in tumor development through defective carcinogen metabolism and/or DNA repair capabilities. GSTP1 plays a key role in detoxification; therefore, underexpression of this gene in tumors of young patients may cause deficient detoxification that could lead to an increased susceptibility to the development of oral carcinoma.

Author Affiliations: Faculte de Medecine Dentaire, Universite Laval, Quebec City, Quebec (Dr Tremblay); Department of Biological and Diagnostic Sciences, Faculty of Dentistry (Drs Tremblay and Bradley), and Departments of Otolaryngology (Dr Freeman) and Laboratory Medicine and Pathobiology (Dr Kamel-Reid), University of Toronto, Toronto, Ontario; Department of Applied Molecular Oncology, Ontario Cancer Institute and Princess Margaret Hospital, University Health Network, Toronto (Drs Tremblay, Pintor dos Reis, Bradley, Galloni, and Kamel-Reid); Department of Pathology, The University Health Network, Toronto (Drs Perez-Ordonez and Kamel-Reid); Department of Otolaryngology and Surgical Oncology, Mount Sinai Hospital, Toronto (Dr Freeman); and Department of Otolaryngology and Surgical Oncology, University of Toronto and Princess Margaret Hospital, University Health Network (Drs Brown, Gilbert, Gullane, and Irish).