A Let-7 MicroRNA SNP in the KRAS 3'UTR is Prognostic in Early-stage Colorectal Cancer

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2011 Oct 14

PMID 21994416

Citations 50

Authors

Kim M Smits

Trupti Paranjape

Sunitha Nallur

Kim A D Wouters

Matty P Weijenberg

Leo J Schouten

Piet A van den Brandt

Fred T Bosman

Joanne B Weidhaas

Manon van Engeland

Affiliations

Soon will be listed here.

Abstract

Purpose: Colorectal cancer (CRC) is a common cause of death worldwide. Tumor-node-metastasis-system stage is currently used to guide therapy decisions but lacks precision. Prognostic biomarkers are needed to refine stratification of patients for chemotherapy but validated biomarkers are not yet available. Recently, a SNP in a lethal-7 (let-7) miRNA complementary site (LCS6) in the KRAS 3'untranslated region was suggested to affect survival in metastatic CRC. Effects in early-stage CRC are however unknown. We studied KRAS-LCS6 genotype, hypothesizing that it might identify early-stage cases with a poor prognosis, and could potentially be used in therapy decision-making.

Experimental Design: We studied 409 early stage, 182 stage III, and 69 stage IV cases, and 1,886 subcohort members from the Netherlands Cohort Study. KRAS-LCS6 genotype was assessed with TaqMan PCR. Kaplan-Meier analyses or Cox regression were used to assess associations between genotype and CRC risk or cause-specific survival.

Results: Early-stage cases with the KRAS-LCS6 variant had a lower CRC risk (incidence-rate ratio 0.68; 95% CI: 0.49-0.94) and a better survival (log-rank P = 0.038; HR 0.46; 95% CI: 0.18-1.14). In patients with KRAS-mutated CRC carrying the KRAS-LCS6 variant, the better outcome was enhanced as no patients died of CRC (log-rank P = 0.017). In advanced patients, no clear association between genotype and CRC risk or survival was observed.

Conclusions: Our results indicate that early-stage CRC cases with the KRAS-LCS6 variant have a better outcome. In advanced disease, the better outcome no longer exists. For early-stage patients, KRAS-LCS6 genotype combined with KRAS mutations merits validation as a prognostic biomarker and consideration in therapy decision-making.

Citing Articles

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Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma.

Marinovic S, Skrtic A, Catela Ivkovic T, Poljak M, Kapitanovic S Hum Cell. 2021; 34(5):1455-1465.

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KRAS gene polymorphisms are associated with the risk of glioma: a two-center case-control study.

Guan Q, Yuan L, Lin A, Lin H, Huang X, Ruan J Transl Pediatr. 2021; 10(3):579-586.

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CircBACH1/let-7a-5p axis enhances the proliferation and metastasis of colorectal cancer by upregulating CREB5 expression.

Li J, Tang Q, Dong W, Wang Y J Gastrointest Oncol. 2021; 11(6):1186-1199.

PMID: 33456992 PMC: 7807282. DOI: 10.21037/jgo-20-498.

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