Clinical—Alimentary TractA Prospective Cohort Study Shows Unique Epigenetic, Genetic, and Prognostic Features of Synchronous Colorectal Cancers
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Study Population
We utilized 2 prospective cohort studies: the Nurses' Health Study (121,701 women followed since 1976)27 and the Health Professionals Follow-up Study (51,529 men followed since 1986).27 Every 2 years, participants have been sent follow-up questionnaires to identify newly diagnosed cancer and other diseases in themselves and their first-degree relatives. For nonresponders, we searched the National Death Index to discover deaths and ascertain any diagnosis of colorectal cancer that contributed to
Clinical Features of Synchronous Colorectal Cancer Cases
During follow-up of the 2 prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), there were 2068 eligible colorectal cancer patients diagnosed up to 2004. Among the 2068 patients, we identified 47 cases of synchronous colorectal cancers (Figure 1). The remaining 2021 solitary colorectal cancers had arisen in the same cohort population that had given rise to the 47 synchronous cases and thus constituted an optimal control group. We assessed clinical
Discussion
In this study, we examined genetic and epigenetic features as well as clinical outcome of synchronous colorectal cancer cases. To date, no previous study has examined global DNA methylation levels within synchronous colorectal cancer pairs. In addition, no previous study has compared clinical and molecular features of synchronous colorectal cancers with those of solitary colorectal cancers that had occurred in the same background population as the synchronous cancers in a prospective cohort
Acknowledgments
The authors thank the Nurses' Health Study and Health Professionals Follow-up Study cohort participants who have generously agreed to provide us with biological specimens and information through responses to questionnaires; hospitals and pathology departments throughout the United States for providing us with tumor tissue materials; Frank Speizer, Walter Willett, Susan Hankinson, Meir Stampfer, and many other staff members who implemented and maintained the cohort studies.
K.N., S.K., and N.I.
References (51)
- et al.
Epigenetic profiling of synchronous colorectal neoplasias by quantitative DNA methylation analysis
Mod Pathol
(2006) - et al.
The mechanism of microsatellite instability is different in synchronous and metachronous colorectal cancer
J Gastrointest Surg
(2005) - et al.
Altered DNA mismatch repair expression in synchronous and metachronous colorectal cancers
Clin Gastroenterol Hepatol
(2008) - et al.
Global loss of imprinting leads to widespread tumorigenesis in adult mice
Cancer Cell
(2005) - et al.
Synchronous carcinoma of the colon and rectum: prognostic and therapeutic implications
Am J Surg
(1989) - et al.
Sensitive sequencing method for KRAS mutation detection by pyrosequencing
J Mol Diagn
(2005) - et al.
CpG island methylator phenotype-low (CIMP-low) in colorectal cancer: possible associations with male sex and KRAS mutations
J Mol Diagn
(2006) - et al.
PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations
Neoplasia
(2008) - et al.
Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis
J Mol Diagn
(2006) - et al.
Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample
J Mol Diagn
(2007)
Correlation of β-catenin localization with cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal cancer
Neoplasia
Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component
Mod Pathol
Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer
Gastroenterology
Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women
Gastroenterology
MGMT promoter methylation and field defect in sporadic colorectal cancer
J Natl Cancer Inst
The case for a genetic predisposition to serrated neoplasia in the colorectum: hypothesis and review of the literature
Cancer Epidemiol Biomarkers Prev
DNA methylation, field effects, and colorectal cancer
J Natl Cancer Inst
P53 expression in synchronous colorectal cancer
Saudi Med J
The role of MLH1, MSH2, and MSH6 in the development of multiple colorectal cancers
Br J Cancer
Microsatellite instability in multiple colorectal tumors
Int J Cancer
Evidence of a preferred molecular pathway in patients with synchronous colorectal cancer
Cancer
The role of hMLH1 methylation in the development of synchronous sporadic colorectal carcinomas
Dis Colon Rectum
Induction of tumors in mice by genomic hypomethylation
Science
A cohort study of tumoral LINE-1 hypomethylation and prognosis in colon cancer
J Natl Cancer Inst
Multiple primary cancer: an experience at the Cancer Institute Hospital with special reference to colorectal cancer
Int J Clin Oncol
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the US National Institutes of Health (P01 CA87969 to S. Hankinson, P01 CA55075 to W. Willett, P50 CA127003 to C.S.F., K07 CA122826 to S.O.); the Bennett Family Fund; the Entertainment Industry Foundation National Colorectal Cancer Research Alliance; and a fellowship grant from the Japan Society for Promotion of Science (to K.N.).
The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. Funding agencies did not have any role in the design of the study; the collection, analysis, or interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript.