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Molecular Cancer

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Open Access 01-12-2012 | Research

SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer

Authors: Felicitas Schmid, Susen Burock, Konrad Klockmeier, Peter M Schlag, Ulrike Stein

Published in: Molecular Cancer | Issue 1/2012

Abstract

Background

Colorectal cancer is one of the main cancers in the Western world. About 90% of the deaths arise from formation of distant metastasis. The expression of the newly identified gene metastasis associated in colon cancer 1 (MACC1) is a prognostic indicator for colon cancer metastasis. Here, we analyzed for the first time the impact of single nucleotide polymorphisms (SNPs) in the coding region of MACC1 for clinical outcome of colorectal cancer patients. Additionally, we screened met proto-oncogene (Met), the transcriptional target gene of MACC1, for mutations.

Methods

We sequenced the coding exons of MACC1 in 154 colorectal tumors (stages I, II and III) and the crucial exons of Met in 60 colorectal tumors (stages I, II and III). We analyzed the association of MACC1 polymorphisms with clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients’ survival (n = 154, stages I, II and III). Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells.

Results

We genotyped three MACC1 SNPs in the coding region. Thirteen % of the tumors had the genotype cg (rs4721888, L31V), 48% a ct genotype (rs975263, S515L) and 84% a gc or cc genotype (rs3735615, R804T). We found no association of these SNPs with clinicopathological parameters or with patients’ survival, when analyzing the entire patients’ cohort. An increased risk for a shorter metastasis-free survival of patients with a ct genotype (rs975263) was observed in younger colon cancer patients with stage I or II (P = 0.041, n = 18). In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation.

Conclusion

In summary, the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients’ survival compared to MACC1 expression analysis alone. The ct genotype (rs975263) might be associated with a reduced survival for younger colon cancer patients in early stages. However, further studies with larger sample sizes are needed.

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Title: SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer
Authors: Felicitas Schmid
Susen Burock
Konrad Klockmeier
Peter M Schlag
Ulrike Stein
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2012
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-11-49

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