Volume 8 Supplement 1

Proceedings of the 13th Annual Meeting of the Collaborative Group of the Americas on Inherited Colorectal Cancer

Open Access

A predictive model of metachronous colorectal cancer occurrence in Lynch syndrome

  • Lucio Bertario1Email author,
  • Paola Sala1,
  • Paolo Radice2, 5,
  • Stefano Signoroni1,
  • Giovanni Ballardini3,
  • Emanuele Meroni3 and
  • Antonio Russo4
Hereditary Cancer in Clinical Practice20108(Suppl 1):O7

https://doi.org/10.1186/1897-4287-8-S1-O7

Published: 25 May 2010

Background

Lynch Syndrome (LS) correlated colorectal carcinoma (CRC) patients show a tendency towards the development of multiple and metachronous lesions and, for this reason, a surgical prophylactic treatment, as total colectomy, is warranted. Considering the quality of life of patients treated with total colectomy, it is essential to determine risk factors of metachronous CRC. Aim of the study was to evaluate through a predictive model the patients that could really benefit from a surgical prevention.

Methods

We considered LS or suspected LS CRC patients enrolled by our Institutional Register of Hereditary Colorectal Tumors and submitted to a surgical resection of CRC, excluding those who had a total colectomy. Patients were characterized according to their genotype (MLH I, MSH2 and MSH6), sex and clinical features (age at diagnosis, tumour site, stage, grading, presence of colorectal adenomas and of extracolonic cancers) and were stratified in 4 mutually exclusive groups according to family characteristics: A) MMR gene mutation positive; B) Amsterdam criteria (ACI-II) positive, but mutation negative; C) AC-like and D) high risk. In order to identify a model for predicting metachronous CRC occurrence, for each patients' group a stepwise unconditional logistic regression model was fitted. All the regression equation included terms for gender, age in continuous as blocked terms. The predictive accuracy was assessed using the area under the receiver operating characteristics curve (AUC).

Results

A total of 1,604 CRC patients (M/F=1.02, 16.5% <40 yrs old) were considered (600 in group A, 117 B, 530 C and 357 D). During the follow-up, 181 developed metachronous CRC (11 %) and 354 (22%) an extracolonic cancer. The risks of metachronous CRC at 10 years were 21%, 16%, 16%, and 14% for group A, B, C and D, respectively. The predictive variables in the final model comprised for each group were: A) MLHI mutation, the presence of colorectal adenomas and then occurrence of extracolonic cancers, B) occurrence of extracolonic cancers, C) high tumor grade and presence of colorectal adenomas. No significant predictors were identified for group D. AUC values, as a measure of discrimination of the various models, were 0.72, 0.78 and 0.76 for group A, B and C, respectively.

Conclusions

Metachronous CRC is a long-term moderate risk in LS patients. This suggests to recommend a prophylactic colectomy only to selected patients with well defined characteristics.

Declarations

Acknowledgement

This study was supported by the Italian Association and Foundation for Cancer Research (AIRC).

Authors’ Affiliations

(1)
Unit of Hereditary Digestive Tumours IRCCS Istituto Nazionale Tumori Foundation
(2)
Department of Experimental Oncology and Molecular Medicine, IRCCS Istituto Nazionale Tumori Foundation
(3)
Unit of Endoscopy IRCCS Istituto Nazionale Tumori Foundation
(4)
Epidemiology Unit, San Carlo Hospital
(5)
FIRC Institute of Molecular Oncology Foundation

Copyright

© Bertario et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

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