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Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.

ABSTRACT: Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA-SSR1 is a dinucleotide CA repeat of the EGFR gene that can modulate EGFR transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for EGFR CA-SSR1 polymorphism and MSI status. Additionally, EGFR mRNA and protein expression levels in the tumour centre and in the invasive tumour front, compared with those in adjacent normal tissue samples, were evaluated in 80 tumour samples. An inverse association was identified between EGFR mRNA levels and the sum of repeats in both alleles of the CA-SSR1 polymorphism in normal tissues. Changes in CA-SSR1 were detected in the tumour centre as well as in the invasive tumour front and metastases in all MSI high (MSI-H) tumours. Analysis of EGFR expression at the mRNA and protein levels according to MSI status revealed lower EGFR mRNA and protein expression in MSI-H tumours than microsatellite-stable (MSS) tumours. Furthermore, higher EGFR levels in the invasive tumour front compared with in the tumour centre in MSS tumours were identified, suggesting a role of EGFR in tumour progression and higher invasive potential of MSS than MSI-H tumours.

SUBMITTER: Marinovic S

PROVIDER: S-EPMC7798105 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.

Marinović Sonja S Vuković Kristina K Škrtić Anita A Poljak Mirko M Petek Sara S Petek Lara L Kapitanović Sanja S

Oncology letters 20201218 2

Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA-SSR1 is a dinucleotide CA repeat of the EGFR gene that can modulate EGFR transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for EGFR CA-SSR1 po ...[more]

PMID: 33552252

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Project description:BackgroundWomen with gestational diabetes mellitus have an increased risk of developing gestational hypertension, which can increase fetal and neonatal morbidity and mortality. In the past decade, single nucleotide polymorphisms in several genes have been identified as risk factors for development of gestational hypertension. The epidermal growth factor receptor activates tyrosine kinase mediated blood vessels contractility; and inflammatory cascades. Abnormalities in these mechanism are known to contribute towards hypertension. It is thus plausible that polymorphisms in the epidermal growth factor receptor gene would be associated with the development of hypertension in women with gestational diabetes.AimTo determine whether the epidermal growth factor receptor rs17337023 SNP is associated with the occurrence of hypertension in gestational diabetic women.MethodsThis pilot case-control study was conducted at two tertiary care hospitals in Karachi, from January 2017-August 2018. Two hundred and two women at 28 week of gestation with gestational diabetes were recruited and classified into normotensive (n = 80) and hypertensive (n = 122) groups. Their blood samples were genotyped for epidermal growth factor receptor polymorphism rs17337023 using tetra-ARMS polymerase chain reaction. Descriptive analysis was applied on baseline data. Polymorphism data was analyzed for genotype and allele frequency determination using chi-squared statistics. In all cases, a P value of < 0.05 was considered significant.ResultsSubjects were age-matched and thus no difference was observed in relation to age of the study subjects (P >0.05). Body fat percentage was significantly higher in hypertensive females as compared to normotensive subjects (35.138 ± 4.29 Case vs 25.01 ± 8.28 Control; P < 0.05). Similarly, systolic and diastolic blood pressures among groups were significantly higher in hypertensive group than the normotensive group (P < 0.05). Overall epidermal growth factor receptor rs17337023 polymorphism genotype frequency was similar in both groups, with the heterozygous AT genotype (56 in Case vs 48 in Control; P = 0. 079) showing predominance in both groups. Furthermore, the odds ratio for A allele was 1.282 (P = 0.219) and for T allele was 0.780 (P = 0.221) in this study.ConclusionThis pilot study indicates that polymorphisms in rs17337023 may not be involved in the pathophysiology of gestational hypertension in gestational diabetes via inflammatory cascade mechanism. Further large-scale studies should explore polymorphism in epidermal growth factor receptor and other genes in this regard.

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Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.

Publications

Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.

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