Document Detail


Prospective study of family history and colorectal cancer risk by tumor LINE-1 methylation level.
MedLine Citation:
PMID:  23175808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Beyond known familial colorectal cancer (CRC) syndromes, the mechanisms underlying the elevated CRC risk associated with CRC family history remain largely unknown. A recent retrospective study suggests familial clustering of CRC with hypomethylation in long interspersed nucleotide element 1 (LINE-1). We tested the hypothesis that CRC family history might confer a higher risk of LINE-1 methylation-low CRC.
METHODS: Using the Nurses' Health Study and the Health Professionals Follow-up Study, we prospectively examined the association between CRC family history and the risk of rectal and colon cancer (N = 1224) according to tumor LINE-1 methylation level by duplication method Cox proportional hazards regression. We examined microsatellite instability (MSI) status to exclude the influence of Lynch syndrome. All statistical tests were two-sided.
RESULTS: The association between CRC family history and non-MSI CRC risk differed statistically significantly by LINE-1 methylation level (P (heterogeneity) = .02). CRC family history was associated with a statistically significantly higher risk of LINE-1 methylation-low non-MSI cancer (multivariable hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.19 to 2.38 for 1 vs 0 first-degree relatives with CRC; multivariable HR = 3.48, 95% CI = 1.59 to 7.6 for ≥2 vs 0 first-degree relatives with CRC; P (trend) < .001). In contrast, CRC family history was not statistically significantly associated with LINE-1 methylation-high non-MSI cancer (P (trend) = .35).
CONCLUSIONS: This molecular pathological epidemiology study shows that CRC family history is associated with a higher risk of LINE-1 methylation-low CRC, suggesting previously unrecognized heritable predisposition to epigenetic alterations. Additional studies are needed to evaluate tumor LINE-1 methylation as a molecular biomarker for familial cancer risk assessment.
Authors:
Shuji Ogino; Reiko Nishihara; Paul Lochhead; Yu Imamura; Aya Kuchiba; Teppei Morikawa; Mai Yamauchi; Xiaoyun Liao; Zhi Rong Qian; Ruifang Sun; Kaori Sato; Gregory J Kirkner; Molin Wang; Donna Spiegelman; Jeffrey A Meyerhardt; Eva S Schernhammer; Andrew T Chan; Edward Giovannucci; Charles S Fuchs
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-21
Journal Detail:
Title:  Journal of the National Cancer Institute     Volume:  105     ISSN:  1460-2105     ISO Abbreviation:  J. Natl. Cancer Inst.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-03-01     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  7503089     Medline TA:  J Natl Cancer Inst     Country:  United States    
Other Details:
Languages:  eng     Pagination:  130-40     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Colorectal Neoplasms / genetics*
CpG Islands / genetics
DNA Methylation*
Epigenesis, Genetic
Female
Humans
Long Interspersed Nucleotide Elements / genetics*
Male
Medical History Taking
Microsatellite Instability
Middle Aged
Odds Ratio
Proportional Hazards Models
Prospective Studies
Risk Assessment
Risk Factors
Grant Support
ID/Acronym/Agency:
CAF/10/15//Chief Scientist Office; P01 CA55075/CA/NCI NIH HHS; P01 CA87969/CA/NCI NIH HHS; P50 CA127003/CA/NCI NIH HHS; R01 CA137178/CA/NCI NIH HHS; R01 CA149222/CA/NCI NIH HHS; R01 CA151993/CA/NCI NIH HHS; R01 CA151993/CA/NCI NIH HHS
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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