Genetic polymorphism of the plasminogen activator inhibitor‐1 is associated with an increased risk of endometrial cancer

Su, Chung‐Kuang; Yeh, Kun‐Tu; Yeh, Chih‐Jung; Wang, Po-Hui; Ho, Esther Shih-Chu; Chou, Ming‐Chih; Liu, Kai-Cheng; Yang, Shun‐Fa; Yi, Yu-Chiao

doi:10.1002/jso.22035

Cited by 13 publications

(13 citation statements)

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“…However, no significant difference in allele frequency was evident between the two. Other criteria for dividing the subjects into various groups were determined according to previous reports as well as clinical significance [4], [5]. The results showed that the SNP C variant carriers had higher pathological grade and deeper myometrial invasion (OR = 2.042 and OR = 2.233 respectively) compared to G carriers.…”

Section: Resultsmentioning

confidence: 99%

Single Nucleotide Polymorphism of SREBF-1 Gene Associated with an Increased Risk of Endometrial Cancer in Chinese Women

Qiu

Dongol

et al. 2014

PLoS ONE

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AimElevated levels of sterol regulatory element-binding protein-1 (SREBP-1) have been found in endometrial cancer (EC), suggesting that it is essential to the development of EC. Obesity and diabetes have been established as known risk factors of EC, while SREBF-1 gene polymorphisms have also been found to be associated with obesity and type II diabetes. Therefore, we hypothesize that single nucleotide polymorphism (SNP) in SREBF-1 gene may be associated with increased risk of EC.MethodWe analyzed the sequence of SREBF-1 in tissue samples from 30 EC cases and 6 benign controls using high throughput method. Based on the primary results, we selected one SNP (rs2297508) as a genetic marker to conduct a hospital-based case-control study with 139 EC cases and 129 benign controls. The samples were examined under the microscope to determine their histopathology prior to the SNP analysis using RT-PCR.ResultsThrough sequence analysis, we found 10 SNPs of SREBF-1 associated with EC, including 3 new SNPs. Fourteen percent of EC showed the rs2297508 SNP with C allele, while only 7% had the C allele was present in benign controls (p = 0.027, OR = 1.983). Additionally, the C allele was associated with cancer differentiation (p<0.05) and the depth of myometrial invasion (p<0.05).ConclusionOur study indicates that SNP (rs2297508) of SREBF-1 may serve as a genetic predisposition factor for the development of EC and screening of such genetic marker may be helpful in its early detection.

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Section: Resultsmentioning

confidence: 99%

Single Nucleotide Polymorphism of SREBF-1 Gene Associated with an Increased Risk of Endometrial Cancer in Chinese Women

Qiu

Dongol

et al. 2014

PLoS ONE

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“…We defined studies that scored ≥7 as having high methodological quality, and we judged 4 (21,22,26,35) of the 21 studies to be of low quality (score of 6) primarily due to the absence of a definition of controls and a lack of a description of comparability between cases and controls.…”

Section: Resultsmentioning

confidence: 99%

“…To date, a number of molecular epidemiological studies have been performed to evaluate the association between PAI-1 promoter 4G/5G polymorphism and risks for different types of tumor, including breast cancer (12–17), colorectal cancer (3,18–20), ovarian cancer (21,22), oral cancer (23,24), endometrial cancer (25,26) and other cancers (27,28), in diverse populations However, the observed associations of these studies were inconsistent and a single study may be insufficient to detect a possible small effect of the polymorphism on cancer, particularly when the sample size is relatively small. Hence, we performed a meta-analysis of all eligible studies to derive a more precise estimation of the association of PAI-1 promoter 4G/5G polymorphism with cancer risk.…”

Section: Introductionmentioning

confidence: 99%

PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis

Xie

Lin

et al. 2012

Experimental and Therapeutic Medicine

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Plasminogen activator inhibitor-1 (PAI-1), belonging to the urokinase plasminogen activation (uPA) system, is involved in cancer development and progression. The PAI-1 promoter 4G/5G polymorphism was shown to contribute to genetic susceptibility to cancer, although the results were inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Scopus, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were searched; data were extracted and analyzed independently by two reviewers. Ultimately, 21 eligible case-control studies with a total of 8,415 cancer cases and 9,208 controls were included. The overall odds ratio (OR) with its 95% confidence interval (CI) showed a statistically significant association between the PAI-1 promoter 4G/5G polymorphism and cancer risk (4G/4G vs. 5G/5G: OR=1.25, 95% CI=1.07–1.47, Pheterogeneity=0.001; 4G/4G vs. 4G/5G+5G/5G: OR=1.10, 95% CI=1.03–1.17, Pheterogeneity=0.194; 4G/4G+4G/5G vs. 5G/5G: OR=1.17, 95% CI=1.01–1.35, Pheterogeneity=0.041). In further subgroup analyses, the increased risk of cancer was observed in a subgroup of Caucasians with regards to endometrial cancer. Our meta-analysis suggests that the PAI-1 4G/5G polymorphism most likely contributes to susceptibility to cancer, particularly in Caucasians. Furthermore, the 4G allele may be associated with an increased risk of endometrial cancer.

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“…And results of study of Vossen et al did not support an effect of PAI 1 4G/5G on colorectal cancer risk [59]. Palmirotta et al [62,63]. For colorectal cancer Försti et al in their work demonstrates that the 4G/4G genotype is associated with shorter survival because it is linked more to Dukes C tumors, in contrast to the 5G/5G genotype, which is associated more with tumors stage A and B [34].…”

Section: Discussionmentioning

confidence: 96%

“…The presence of 4G/4G genotype in the promoter of the PAI 1 gene increases the risk of thrombosis. This polymorphism is also often associated with other diseases such as heart attack [24] or diabetes mellitus [25], and with other types of cancers such as endometrial cancer or breast cancer [26,27]. The distribution of each variant is different in different populations, the 4G/4G genotype is more common among Asians (59%) [28] and Caucasian populations (51%) [29], Spaniards (47%) [30] and Indians (54%) [31], than for Mexicans (34%) [32] and African-Americans (24%) [33].…”

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confidence: 99%

Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients

Halámková

Kiss²,

Pavlovský³

et al. 2012

neo

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Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

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Genetic polymorphism of the plasminogen activator inhibitor‐1 is associated with an increased risk of endometrial cancer

Abstract: Individuals with PAI-1 rs1799889 4G/4G genotype were at significantly higher risk of endometrial cancer in this study.

Cited by 13 publications

References 30 publications

Single Nucleotide Polymorphism of SREBF-1 Gene Associated with an Increased Risk of Endometrial Cancer in Chinese Women

Single Nucleotide Polymorphism of SREBF-1 Gene Associated with an Increased Risk of Endometrial Cancer in Chinese Women

PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis

Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients

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