Single nucleotide polymorphism of pi-class glutathione s-transferase and susceptibility to endometrial carcinoma.
OBJECTIVE
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.


METHODS
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(105)Val 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.
Chan
Queeny K Y
QK
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Khoo
Ui-Soon
US
Ngan
Hextan Y S
HY
Yang
Chong-Qing
CQ
Xue
Wei-Cheng
WC
Chan
Kelvin Y K
KY
Chiu
Pui-Man
PM
Ip
Philip P C
PP
Cheung
Annie N Y
AN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D004273:DNA, Neoplasm; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase