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Assessing the ProMCol classifier as a prognostic marker for non-metastatic colorectal cancer within the Melbourne Collaborative Cohort Study
  1. Jihoon E Joo1,2,
  2. Harindra Jayasekara1,2,3,4,
  3. Ee Ming Wong5,6,
  4. Mark Clendenning1,2,
  5. Christophe Rosty1,2,7,8,
  6. Ingrid M Winship9,10,
  7. Mark A Jenkins11,
  8. John L Hopper11,
  9. Dallas R English3,11,
  10. Roger L Milne3,11,
  11. Graham G Giles3,11,
  12. Melissa C Southey2,5,6,
  13. Daniel D Buchanan1,2,10,11
  1. 1 Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
  2. 2 Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, Victoria, Australia
  3. 3 Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia
  4. 4 Centre for Alcohol Policy Research, La Trobe University, Melbourne, Victoria, Australia
  5. 5 Precision Medicine, Monash University, Clayton, Victoria, Australia
  6. 6 Genetic Epidemiology Laboratory, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
  7. 7 Envoi Pathology, Brisbane, Queensland, Australia
  8. 8 School of Medicine, University of Queensland, Herston, Queensland, Australia
  9. 9 Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
  10. 10 Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  11. 11 Centre for Epidemiology and Biostatistics, The University of Melbourne, Carlton, Victoria, Australia
  1. Correspondence to Associate Professor Daniel D Buchanan, Colorectal Oncogenomics Group, Department of Clinical, PathologyThe University of Melbourne, Melbourne, VIC 3010, Australia; daniel.buchanan{at}unimelb.edu.au

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We read with interest the work by Gündert and colleagues, which describes a new prognostic classifier for non-metastatic colorectal cancer (CRC), ProMCol, derived from DNA methylation levels at 20 CpG sites in colorectal tumour tissue.1 Here, we tested the ProMCol classifier on an independent cohort of 526 non-metastatic CRC tumours from the Melbourne Collaborative Cohort Study (MCCS). The MCCS is a prospective cohort study of 41 513 healthy adult volunteers recruited between 1990 and 1994.2 By 31 December 2009, 1046 participants had a first histopathological diagnosis of invasive adenocarcinoma of the colon or rectum identified through the Victorian Cancer Registry (VCR) following the baseline study visit (a total of 1101 CRCs). Characterisation of this CRC-affected cohort is described in Buchanan et al.3 Vital status was ascertained through the VCR and the National Death Index.

From all 1046 participants with a CRC diagnosis, we excluded 26 tumours with the tumour site listed as overlapping lesions of rectum, anus and anal canal (International Statistical Classification of Diseases and Related Health Problems 10th Revision code C21.8) or had unknown site, we removed 228 tumours without available formalin-fixed paraffin embedded (FFPE) tissue specimens, a further 142 tumours were unavailable for DNA methylation testing, and finally we removed 124 metastatic cases (stage 4 American Joint Committee on Cancer (AJCC)) and tumours with unknown stages, leaving a total of 526 CRC tumours …

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Footnotes

  • MCS and DDB contributed equally.

  • Contributors This study was first conceived by JEJ, HJ and DDB. EMW and JEJ performed laboratory experiments. JEJ and HJ performed bioinformatics and statistical analysis. HJ, DRE, RLM, GGG and DDB faciliated the inclusion of the data from the MCCS. MC and CR provided molecular characterisation and paghological review of FFPE slides, respectively. The manuscript was first constructed by JEJ, HJ and DDB. MC, CR, IMW, MAJ, JLH, DRE, RLM, GGG and MCS provided critical reviews of the analysis and the manuscript. All authors reviewed and approved the final manuscript.

  • Funding This project was supported by grant from the National Health and Medical Research Council (NHMRC) (grant 1027505). MCCS recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. Cases were ascertained through the Victorian Cancer Registry (VCR) and the Australian Cancer Database (Australian Institute of Health and Welfare). HJ is supported by a Victorian Cancer Agency Early Career Seed Grant Fellowship. MCS is a Senior Research Fellow and JLH is a Senior Principle Research Fellow of the NHMRC. DDB is a NHMRC RD Wright Biomedical Fellow.

  • Disclaimer Authors had full responsibility for the design of the study, the collection of the data, the analysis and interpretaion of the data, the decision to submit the manuscript for publication and the writing of the manuscript.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval This study was approved by the Cancer Council Victoria Human Research Ethics Committee (IEC No. 9001).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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