Serrated neoplasia pathway as an alternative route of colorectal cancer carcinogenesis

Context.—Colorectal cancer is a heterogeneous disease entity with 3 molecular carcinogenesis pathways and 2 morphologic multistep pathways. Right-sided colon cancers and left-sided colon and rectal cancers exhibit differences in their incidence rates according to geographic region, age, and sex. A linear tendency toward increasing frequencies of microsatellite instability–high or CpG island methylator phenotype–high cancers in subsites along the bowel from the rectum to the cecum or the ascending colon accounts for the differences in tumor phenotypes associated with these subsites. The molecular subtypes of colorectal cancers exhibit different responses to adjuvant therapy, which might be responsible for differences in subtype-specific survival. Objectives.—To review the clinicopathologic and molecular features of the molecular subtypes of colorectal cancer generated by combined CpG island methylator phenotype and microsatellite statuses, to integrate these features with the most recent findings in the context of the prognostic implications of molecular subtypes, and to emphasize the necessity of developing molecular markers that enable the identification of adenocarcinomas involving the serrated neoplasia pathway. Data Sources.—Based on the authors' own experimental data and a review of the pertinent literature. Conclusions.—Because colorectal cancers arise from 2 different morphologic multistep carcinogenesis pathways with varying contributions from 3 different molecular carcinogenesis pathways, colorectal cancer is a heterogeneous and complex disease. Thus, molecular subtyping of colorectal cancers is an important approach to characterizing their heterogeneity with respect to not only prognosis and therapeutic response but also biology and natural history.

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Notch signaling promotes serrated neoplasia pathway in colorectal cancer through epigenetic modification of EPHB2 and EPHB4

Cancer Management and Research ◽

10.2147/cmar.s178126 ◽

2018 ◽

Vol Volume 10 ◽

pp. 6129-6141 ◽

Cited By ~ 5

Author(s):

Haifeng Lian ◽

Xingfang Jia ◽

Ning Shi ◽

Shuyang Xie ◽

Jian Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Notch Signaling ◽

Epigenetic Modification ◽

Serrated Neoplasia Pathway

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Serrated pathway: Alternative route to colorectal cancer

World Journal of Gastroenterology ◽

10.3748/wjg.v19.i5.607 ◽

2013 ◽

Vol 19 (5) ◽

pp. 607 ◽

Cited By ~ 41

Author(s):

Árpád V Patai

Keyword(s):

Colorectal Cancer ◽

Alternative Route ◽

Serrated Pathway

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Nut and peanut butter intake and the risk of colorectal cancer and its anatomical and molecular subtypes: the Netherlands Cohort Study

Carcinogenesis ◽

10.1093/carcin/bgaa080 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1368-1384

Author(s):

Lisette Nieuwenhuis ◽

Colinda C J M Simons ◽

Matty P Weijenberg ◽

Piet A van den Brandt

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Cohort Study ◽

Cancer Risk ◽

Peanut Butter ◽

Colorectal Tumors ◽

Increased Risk ◽

Nut Intake ◽

Serrated Neoplasia Pathway

Abstract Nut intake has been associated with reduced total cancer-related mortality, but evidence for colorectal cancer (CRC) risk is inconclusive. We investigated the associations between nut and peanut butter intake and anatomical CRC subtypes. To account for molecular heterogeneity, associations between nut and peanut butter intake and colorectal tumors harboring APC, KRAS or BRAF mutations, p53 overexpression or microsatellite instability were examined in secondary analyses. In the Netherlands Cohort Study (n = 120 852), lifestyle habits were measured with a questionnaire in 1986. After 20.3 years follow-up, 3567 CRC cases were included in case–cohort analyses. For the analyses of molecular CRC subtypes, 574 cases were included after 7.3 years follow-up. In categorical analyses, total nut intake was not significantly associated with CRC [HR (95% CI) 10+ g/day versus non-consumers = 0.94(0.78–1.15) in men; 0.96(0.75–1.22) in women]. In restricted cubic spline analyses, significant non-linear inverse associations with rectal cancer were observed for total nut, peanut and peanut butter intake in women, and borderline significant non-linear inverse associations for total nut and peanut intake in men. Regarding the molecular CRC subtypes, peanut butter intake was significantly associated with an increased risk of colorectal tumors that did not develop through the serrated neoplasia pathway in men [HR (95% CI) per 5 g/day increment = 1.22(1.07–1.38)]. Nut and peanut butter intake are non-linearly inversely associated with rectal cancer risk in women. In men, nut intake is borderline significantly non-linearly associated with a reduced rectal cancer risk. Peanut butter is associated with an increased risk of colorectal tumors that do not develop through the serrated neoplasia pathway in men.

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