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Article: Single nucleotide polymorphism of Pi-class glutathione S-transferase and susceptibility to endometrial carcinoma

TitleSingle nucleotide polymorphism of Pi-class glutathione S-transferase and susceptibility to endometrial carcinoma
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2005, v. 11 n. 8, p. 2981-2985 How to Cite?
AbstractPurpose: Endometrial carcinoma is the most common gynecologic cancer in developed countries. Prolonged unopposed estrogen exposure has been identified as the major risk factor. The pi-class glutathione S-transferase (GSTP1) is a phase II metabolic enzyme that is important in the detoxification of a wide range of electrophiles including carcinogenic steroid-hormone intermediates generated through oxidative metabolism. In this study, we aimed at determining the association between the GSTP1 polymorphism and the risk of endometrial carcinoma in a Chinese population. Experimental Design: Genotyping of 180 cases and 200 age-matched controls were assessed by PCR-RFLP approach and confirmed by direct sequencing. Results: Statistical analysis showed that patients of valine allele carriers had 2.03-fold of increased risk of developing endometrial carcinoma (P < 0.01). The allele frequencies for the Ile and Val variants between the cancer cases and controls were also significantly different (P < 0.01; odds ratio, 1.59; 95% confidence interval, 1.13-2.23). Such association was shown in endometrial cancers as a group and in type I endometrioid adenocarcinoma but not the type II nonendometrioid adenocarcinoma. In addition, the Val allele was found significantly associated with high-grade endometrial cancer and/or endometrial cancer of deep myometrial invasion (P < 0.01). Interestingly, the relatively low frequency of Val/Val genotype in both the cancer cases and controls, in parallel with the lower incidence of endometrial cancer in Chinese, was observed when compared with those in Caucasians. Conclusions: Our findings suggested that the GSTP1 Ile 105Val polymorphism was associated with an increased risk of endometrial cancer. Further studies may be required to explore the possible significance of these polymorphisms on GSTP1-related metabolism that may affect the susceptibility of Asians to endometrial carcinoma. © 2005 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/87101
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, QKYen_HK
dc.contributor.authorKhoo, USen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorYang, CQen_HK
dc.contributor.authorXue, WCen_HK
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorChiu, PMen_HK
dc.contributor.authorIp, PPCen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-09-06T09:25:20Z-
dc.date.available2010-09-06T09:25:20Z-
dc.date.issued2005en_HK
dc.identifier.citationClinical Cancer Research, 2005, v. 11 n. 8, p. 2981-2985en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/87101-
dc.description.abstractPurpose: Endometrial carcinoma is the most common gynecologic cancer in developed countries. Prolonged unopposed estrogen exposure has been identified as the major risk factor. The pi-class glutathione S-transferase (GSTP1) is a phase II metabolic enzyme that is important in the detoxification of a wide range of electrophiles including carcinogenic steroid-hormone intermediates generated through oxidative metabolism. In this study, we aimed at determining the association between the GSTP1 polymorphism and the risk of endometrial carcinoma in a Chinese population. Experimental Design: Genotyping of 180 cases and 200 age-matched controls were assessed by PCR-RFLP approach and confirmed by direct sequencing. Results: Statistical analysis showed that patients of valine allele carriers had 2.03-fold of increased risk of developing endometrial carcinoma (P < 0.01). The allele frequencies for the Ile and Val variants between the cancer cases and controls were also significantly different (P < 0.01; odds ratio, 1.59; 95% confidence interval, 1.13-2.23). Such association was shown in endometrial cancers as a group and in type I endometrioid adenocarcinoma but not the type II nonendometrioid adenocarcinoma. In addition, the Val allele was found significantly associated with high-grade endometrial cancer and/or endometrial cancer of deep myometrial invasion (P < 0.01). Interestingly, the relatively low frequency of Val/Val genotype in both the cancer cases and controls, in parallel with the lower incidence of endometrial cancer in Chinese, was observed when compared with those in Caucasians. Conclusions: Our findings suggested that the GSTP1 Ile 105Val polymorphism was associated with an increased risk of endometrial cancer. Further studies may be required to explore the possible significance of these polymorphisms on GSTP1-related metabolism that may affect the susceptibility of Asians to endometrial carcinoma. © 2005 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.en_HK
dc.relation.ispartofClinical Cancer Researchen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshCarcinoma, Endometrioid - enzymology - genetics - pathologyen_HK
dc.subject.meshDNA Mutational Analysisen_HK
dc.subject.meshDNA, Neoplasm - chemistry - genetics - metabolismen_HK
dc.subject.meshEndometrial Neoplasms - enzymology - genetics - pathologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Frequencyen_HK
dc.subject.meshGenetic Predisposition to Disease - geneticsen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshGlutathione S-Transferase pien_HK
dc.subject.meshGlutathione Transferase - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIsoenzymes - geneticsen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshPolymorphism, Restriction Fragment Lengthen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshRisk Factorsen_HK
dc.titleSingle nucleotide polymorphism of Pi-class glutathione S-transferase and susceptibility to endometrial carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-0432&volume=11&issue=8&spage=2981&epage=2985&date=2005&atitle=Single+nucleotide+polymorphism+of+Pi-Class+glutathione+S-transferase+and+susceptibility+to+endometrial+carcinomaen_HK
dc.identifier.emailKhoo, US: uskhoo@hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailChan, KYK: kelvinc@pathology.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-04-2038en_HK
dc.identifier.pmid15837751-
dc.identifier.scopuseid_2-s2.0-17144395926en_HK
dc.identifier.hkuros101875en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-17144395926&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.issue8en_HK
dc.identifier.spage2981en_HK
dc.identifier.epage2985en_HK
dc.identifier.isiWOS:000228406300025-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, QKY=8390404100en_HK
dc.identifier.scopusauthoridKhoo, US=7004195799en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridYang, CQ=8390403300en_HK
dc.identifier.scopusauthoridXue, WC=7103165268en_HK
dc.identifier.scopusauthoridChan, KYK=7406034195en_HK
dc.identifier.scopusauthoridChiu, PM=7103182596en_HK
dc.identifier.scopusauthoridIp, PPC=7003622683en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.issnl1078-0432-

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