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

ABSTRACT: To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features.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.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.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.

SUBMITTER: Win AK

PROVIDER: S-EPMC4180004 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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

Win Aung Ko AK Buchanan Daniel D DD Rosty Christophe C MacInnis Robert J RJ Dowty James G JG Dite Gillian S GS Giles Graham G GG Southey Melissa C MC Young Joanne P JP Clendenning Mark M Walsh Michael D MD Walters Rhiannon J RJ Boussioutas Alex A Smyrk Thomas C TC Thibodeau Stephen N SN Baron John A JA Potter John D JD Newcomb Polly A PA Le Marchand Loïc L Haile Robert W RW Gallinger Steven S Lindor Noralane M NM Hopper John L JL Ahnen Dennis J DJ Jenkins Mark A MA

Gut 20140310 1

<h4>Objective</h4>To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features.<h4>Design</h4>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 ...[more]

PMID: 24615377

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

Publications

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

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