The association of tumor microsatellite instability phenotype with family history of colorectal cancer

Reference details

Bapat B, Lindor NM, Baron J, Siegmund K, Li L, Zheng Y, Haile R, Gallinger S, Jass JR, Young JP, Cotterchio M, Jenkins M, Grove J, Casey G, Thibodeau SN, Bishop DT, Hopper JL, Ahnen D, Newcomb PA, Le Marchand L, Potter JD, Seminara D (2009) The association of tumor microsatellite instability phenotype with family history of colorectal cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 18:967-975

ABTRACT

Family history is a strong predictor of colorectal cancer risk; however, a diagnosis of colorectal cancer among first-degree relatives has not been systematically investigated as a function of the colorectal cancer molecular subtypes related to tumor microsatellite instability (MSI) status. We investigated whether the observable familial colorectal cancer risks differed according to tumor MSI subtypes, stratified as MSI-High (>30% instability), MSI-Low (<30% instability),="" and="" mss="" (no="" instability).="" data="" from="" 3,143="" population-based="" colorectal="" cancer="" cases="" from="" five="" institutions="" were="" assessed="" for="" family="" history="" according="" to="" the="" amsterdam="" criteria="" and="" the="" bethesda="" guidelines,="" age="" at="" diagnosis,="" sex,="" tumor="" location,="" and="" msi="" status.="" the="" distribution="" of="" patient="" characteristics="" by="" msi="" status="" was="" compared="" using="" polytomous="" logistic="" regression.="" overall,="" 2.8%="" colorectal="" cancer="" cases="" met="" the="" amsterdam="" criteria="" and="" 37%="" met="" the="" bethesda="" guidelines.="" there="" were="" 14%="" msi-high,="" 13%="" msi-low,="" and="" 73%="" mss="" colorectal="" cancers.="" msi-high=""><0.0001) and="" msi-low="" tumors="" (p="0.01)" were="" more="" proximally="" located="" than="" mss="" tumors.="" msi-high="" tumors="" were="" more="" common="" among="" females=""><0.001). the="" highest="" proportion="" of="" msi-high="" tumors="" occurred="" in=""><40 years="" of="" age="" whereas="" the="" age-dependent="" distribution="" of="" msi-low="" tumors="" was="" unchanged.="" msi-high="" tumors="" showed="" a="" statistically="" significant="" association="" with="" increasing="" numbers="" of="" first-degree="" relatives="" with="" colorectal="" cancer="" (p="0.002);" this="" association="" disappeared,="" however,="" when="" msi-high="" cases="" meeting="" amsterdam="" criteria="" were="" removed="" from="" the="" analysis.="" msi-low="" tumors="" did="" not="" show="" a="" similar="" association="" with="" family="" history="" of="" colorectal="" cancer.="" familial="" risk="" associated="" with="" msi-high="" tumors="" is="" primarily="" driven="" by="" the="" amsterdam-criteria="" patients.="" msi-low="" tumors="" may="" represent="" a="" distinct="" subtype="" of="" colorectal="" cancer="" with="" respect="" to="" certain="" epidemiologic="" variables="" studied="">

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