Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives

Aung K. 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 Christopher Smyrk, Stephen N Thibodeau, John A. Baron, John D. Potter, Polly A. Newcomb, Loïc Le Marchand, Robert W. HaileSteven Gallinger, Noralane Morey Lindor, John L. Hopper, Dennis J. Ahnen, Mark A. Jenkins

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)101-110
Number of pages10
JournalGut
Volume64
Issue number1
DOIs
StatePublished - Jan 1 2015

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Molecular Pathology
Colorectal Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Neoplasms
DNA Mismatch Repair
Colonic Neoplasms
Registries
Tumor-Infiltrating Lymphocytes
Canada
Lymphocytes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Win, A. K., Buchanan, D. D., Rosty, C., MacInnis, R. J., Dowty, J. G., Dite, G. S., ... Jenkins, M. A. (2015). Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives. Gut, 64(1), 101-110. https://doi.org/10.1136/gutjnl-2013-306567

Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives. / Win, Aung K.; Buchanan, Daniel D.; Rosty, Christophe; MacInnis, Robert J.; Dowty, James G.; Dite, Gillian S.; Giles, Graham G.; Southey, Melissa C.; Young, Joanne P.; Clendenning, Mark; Walsh, Michael D.; Walters, Rhiannon J.; Boussioutas, Alex; Smyrk, Thomas Christopher; Thibodeau, Stephen N; Baron, John A.; Potter, John D.; Newcomb, Polly A.; Le Marchand, Loïc; Haile, Robert W.; Gallinger, Steven; Lindor, Noralane Morey; Hopper, John L.; Ahnen, Dennis J.; Jenkins, Mark A.

In: Gut, Vol. 64, No. 1, 01.01.2015, p. 101-110.

Research output: Contribution to journalArticle

Win, AK, Buchanan, DD, Rosty, C, MacInnis, RJ, Dowty, JG, Dite, GS, Giles, GG, Southey, MC, Young, JP, Clendenning, M, Walsh, MD, Walters, RJ, Boussioutas, A, Smyrk, TC, Thibodeau, SN, Baron, JA, Potter, JD, Newcomb, PA, Le Marchand, L, Haile, RW, Gallinger, S, Lindor, NM, Hopper, JL, Ahnen, DJ & Jenkins, MA 2015, 'Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives', Gut, vol. 64, no. 1, pp. 101-110. https://doi.org/10.1136/gutjnl-2013-306567
Win, Aung K. ; Buchanan, Daniel D. ; Rosty, Christophe ; MacInnis, Robert J. ; Dowty, James G. ; Dite, Gillian S. ; Giles, Graham G. ; Southey, Melissa C. ; Young, Joanne P. ; Clendenning, Mark ; Walsh, Michael D. ; Walters, Rhiannon J. ; Boussioutas, Alex ; Smyrk, Thomas Christopher ; Thibodeau, Stephen N ; Baron, John A. ; Potter, John D. ; Newcomb, Polly A. ; Le Marchand, Loïc ; Haile, Robert W. ; Gallinger, Steven ; Lindor, Noralane Morey ; Hopper, John L. ; Ahnen, Dennis J. ; Jenkins, Mark A. / Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives. In: Gut. 2015 ; Vol. 64, No. 1. pp. 101-110.
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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.",
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T1 - Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives

AU - Win, Aung K.

AU - Buchanan, Daniel D.

AU - Rosty, Christophe

AU - MacInnis, Robert J.

AU - Dowty, James G.

AU - Dite, Gillian S.

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Young, Joanne P.

AU - Clendenning, Mark

AU - Walsh, Michael D.

AU - Walters, Rhiannon J.

AU - Boussioutas, Alex

AU - Smyrk, Thomas Christopher

AU - Thibodeau, Stephen N

AU - Baron, John A.

AU - Potter, John D.

AU - Newcomb, Polly A.

AU - Le Marchand, Loïc

AU - Haile, Robert W.

AU - Gallinger, Steven

AU - Lindor, Noralane Morey

AU - Hopper, John L.

AU - Ahnen, Dennis J.

AU - Jenkins, Mark A.

PY - 2015/1/1

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N2 - 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.

AB - 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.

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