Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/93992
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Type: Journal article
Title: Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives
Author: Win, A.
Buchanan, D.
Rosty, C.
MacInnis, R.
Dowty, J.
Dite, G.
Giles, G.
Southey, M.
Young, J.
Clendenning, M.
Walsh, M.
Walters, R.
Boussioutas, A.
Smyrk, T.
Thibodeau, S.
Baron, J.
Potter, J.
Newcomb, P.
Le Marchand, L.
Haile, R.
et al.
Citation: Gut, 2015; 64(1):101-110
Publisher: BMJ Publishing Group
Issue Date: 2015
ISSN: 0017-5749
1468-3288
Statement of
Responsibility: 
Aung Ko Win, Daniel D Buchanan, Christophe Rosty, Robert J MacInnis, James G Dowty, Gillian S Dite, Graham G Giles, Melissa C Southey, Joanne P Young, Mark Clendenning, Michael D Walsh, Rhiannon J Walters, Alex Boussioutas, Thomas C Smyrk, Stephen N Thibodeau, John A Baron, John D Potter, Polly A Newcomb, Loïc Le Marchand, Robert W Haile, Steven Gallinger, Noralane M Lindor, John L Hopper, Dennis J Ahnen, Mark A Jenkins
Abstract: OBJECTIVE: To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features. DESIGN: We studied a cohort of 33,496 first-degree relatives of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28,156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands. We compared CRC risk for first-degree relatives stratified by the absence or presence of specific tumour molecular pathology features in probands across each of these four groups and for all groups combined. RESULTS: Compared with first-degree relatives of MMR-proficient CRC cases, a higher risk of CRC was estimated for first-degree relatives of CRC cases with suspected Lynch syndrome (HR 2.06, 95% CI 1.59 to 2.67) and with Lynch syndrome (HR 5.37, 95% CI 4.16 to 6.94), but not with MMR-deficient non-Lynch syndrome (HR 1.04, 95% CI 0.82 to 1.31). A greater risk of CRC was estimated for first-degree relatives if CRC cases were diagnosed before age 50 years, had proximal colon cancer or if their tumours had any of the following: expanding tumour margin, peritumoral lymphocytes, tumour-infiltrating lymphocytes or synchronous CRC. CONCLUSIONS: Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors.
Keywords: Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Risk Assessment; Cohort Studies
Rights: © 2015 BMJ Publishing Group Ltd & British Society of Gastroenterology.
RMID: 0030012008
DOI: 10.1136/gutjnl-2013-306567
Grant ID: http://purl.org/au-research/grants/nhmrc/1042021
Appears in Collections:Medicine publications

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