Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients

Masood, Nosheen; Kayani, Mahmood Akhtar

doi:10.1590/s1415-47572011005000034

Cited by 15 publications

(5 citation statements)

References 26 publications

(36 reference statements)

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“…In current study statistically significant downregulation of GSTP1 was observed in brain tumor samples compared to control samples. Similar results have also been observed in breast cancer (Erlap et al, 2013), prostate cancer (Okino et al, 2007;Re et al, 2011) and colon cancer (Ritchie et al, 2009).Whereas conflicting results for GSTP1 expression pattern have been reported in some of other studies (Masood et al, 2011;Uchida et al, 2013). In present study, significant down-regulation of GSTP1 was observed in more advance grade of brain tumor samples when compared with early grade of brain tumor.…”

Section: Discussionsupporting

confidence: 88%

“…Similar results have also been observed in lung cancer and human endothelial cell (Shah et al, 2009;Conway et al, 2009). Whereas conflicting results for CYP1A1 expression pattern have been reported in some of other studies in different cancers (Chang et al, 2007;Masood et al, 2011;Hafeez et al, 2012). Significant upregulation of CYP1A1 was observed in different types of brain tumors in current study.…”

Section: Discussioncontrasting

confidence: 84%

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Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Wahid¹,

Mahjabeen²,

Baig³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

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Section: Discussionsupporting

confidence: 88%

Section: Discussioncontrasting

confidence: 84%

Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Wahid¹,

Mahjabeen²,

Baig³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Upper aerodigestive tract malignancies constitute 4-5% of all malignancies. It is the sixth most common cancer worldwide and constitutes a significant global problem with half of a million new cases diagnosed every year resulting in an average mortality rate of 7.3 and 3.2 per 100,000 males and females respectively [ 3 ]. In South East Asia, it is the second most common cancer.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of touch imprint cytology for head and neck malignancies: a useful intra-operative tool in resource limited countries

Naveed¹,

Abid²,

Hashmi

et al. 2017

BMC Clin Pathol

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BackgroundIntraoperative consultation is an important tool for the evaluation of the upper aerodigestive tract (UAT) malignancies. Although frozen section analysis is a preferred method of intra-operative consultation, however in resource limited countries like Pakistan, this facility is not available in most institutes; therefore, we aimed to evaluate the diagnostic accuracy of touch imprint cytology for UAT malignancies using histopathology of the same tissue as gold standard.MethodsThe study involved 70 cases of UAT lesions operated during the study period. Intraoperatively, after obtaining the fresh biopsy specimen and prior to placing them in fixative, each specimen was imprinted on 4-6 glass slides, fixed immediately in 95% alcohol and stained with Hematoxylin and Eosin stain. After completion of the cytological procedure, the surgical biopsy specimen was processed. The slides of both touch Imprint cytology and histopathology were examined by two consultant histopathologists.ResultsThe result of touch imprint cytology showed that touch imprint cytology was diagnostic in 68 cases (97.1%), 55 (78.6%) being malignant, 2 cases (2.9%) were suspicious for malignancy, 11 cases (15.7%) were negative for malignancy while 2 cases (2.9%) were false negative. Amongst the 70 cases, 55 cases (78.6%) were malignant showing squamous cell carcinoma in 49 cases (70%), adenoid cystic carcinoma in 2 cases (2.9%), non-Hodgkin lymphoma 2 cases (2.9%), Mucoepidermoid carcinoma 1 case (1.4%), spindle cell sarcoma in 1 case (1.4%). Two cases (2.9%) were suspicious of malignancy showing atypical squamoid cells on touch imprint cytology, while 13 cases (18.6%) were negative for malignancy, which also included 2 false negative cases. The overall diagnostic accuracy of touch imprint cytology came out to be 96.7% with a sensitivity and specificity of 96 and 100%, respectively while PPV and NPV of touch imprint cytology was found to be 100 and 84%, respectively.ConclusionOur experience in this study has demonstrated that touch imprint cytology provides reliable specific diagnoses and can be used as an adjunct to histopathology, particularly in developing countries, where the facility of frozen section is often not available, since a rapid preliminary diagnosis may help in the surgical management planning.

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“…In patients with pharyngeal and laryngeal cancer, 42 head and neck cancer 43 two intronic deletions in the non‐coding regions of human GSTP1 were found – C1074 in intron 3 and C1466 in intron 4 that may result in differential binding of putative regulatory proteins. Lo and Ali‐Osman 44 identified a p53‐binding motif in intron 4 of human GSTP1 by which a wild‐type p53 regulates expression of gene and this could lead to protection against genotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with pharyngeal and laryngeal cancer, 42 head and neck cancer 43 Lo and Ali-Osman 41,45 demonstrated that in intron 5 of human GSTP1 contains retinoic acid response elements that are responsible for induction of gene expression. We found 6 SNPs, 1 deletion and 1 insertion in this canine GSTP1 intron.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism of glutathione S‐transferase P1 of dogs with mammary tumours

Fedets

Dmytruk

Adaszek

et al. 2023

Vet Comparative Oncology

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Mammary tumours constitute more than half of neoplasms in female dogs from different countries. Genome sequences are associated with cancer susceptibility but there is little information available about genetic polymorphisms of glutathione S‐transferase P1 (GSTP1) in canine cancers. The aim of this study was to find single nucleotide polymorphisms (SNPs) in GSTP1 of dogs (Canis lupus familiaris) with mammary tumours compared to healthy dogs and to determine the association between GSTP1 polymorphisms and the occurrence of these tumours. The study population included 36 client‐owned female dogs with mammary tumours and 12 healthy female dogs, with no previous diagnosis of cancer. DNA was extracted from blood and amplified by PCR assay. PCR‐products were sequenced by Sanger method and analysed manually. The 33 polymorphisms were found in GSTP1: 1 coding SNP (exon 4), 24 non‐coding SNPs (9 in exon 1), 7 deletions and 1 insertion. The 17 polymorphisms have been found in introns 1, 4, 5 and 6. The dogs with mammary tumours have significant difference from healthy in SNPs I4 c.1018 + 123 T > C (OR 13.412, 95%CI 1.574–114.267, P = .001), I5 c.1487 + 27 T > C (OR 10.737, 95%CI 1.260–91.477, P = .004), I5 c.1487 + 842 G > C (OR 4.714, 95% CI 1.086–20.472, P = .046) and I6 c.2481 + 50 A > G (OR 12.000, 95% CI 1.409–102.207, P = .002). SNP E5 c.1487 T > C and I5 c.1487 + 829 delG also differed significantly (P = .03) but not to the confidence interval. The study, for the first time, showed a positive association of SNPs in GSTP1 with mammary tumours of dogs, that can possibly be used to predict the occurrence of this pathology.

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Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients

Cited by 15 publications

References 26 publications

Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Diagnostic accuracy of touch imprint cytology for head and neck malignancies: a useful intra-operative tool in resource limited countries

Polymorphism of glutathione S‐transferase P1 of dogs with mammary tumours

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