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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors

Authors: Adam Naguib, James C Cooke, Lisa Happerfield, Lucy Kerr, Laura J Gay, Robert N Luben, Richard Y Ball, Panagiota N Mitrou, Alison McTaggart, Mark J Arends

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions.

Methods

186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires.

Results

Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55).

Conclusion

These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.
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Metadata
Title
Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors
Authors
Adam Naguib
James C Cooke
Lisa Happerfield
Lucy Kerr
Laura J Gay
Robert N Luben
Richard Y Ball
Panagiota N Mitrou
Alison McTaggart
Mark J Arends
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-123

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