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Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX

Cited 17 time in Web of Science Cited 15 time in Scopus
Authors
Lee, Dae-Won; Han, Sae-Won; Cha, Yongjun; Rhee, Ye Young; Bae, Jeong Mo; Cho, Nam-Yun; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue; Jeong, Seung-Yong; Park, Kyu Joo; Kang, Gyeong Hoon; Kim, Tae-You
Issue Date
2015-07
Publisher
BioMed Central
Citation
Clinical Epigenetics, Vol.7, p. 63
Keywords
Colorectal cancerCpG islands methylator phenotypeSexFOLFOX
Description
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly credited.
Abstract
Background: Profound methylation of CpG islands constitutes a distinct molecular subtype of colorectal cancer (CRC). The frequencies of methylation in CRC vary according to clinico-pathological characteristics including sex. However, interaction between these characteristics and prognostic influence of methylation status has not been clearly defined. We have investigated the prognostic role of promoter methylation using eight CpG island methylator phenotype (CIMP) markers in 497 stage II or III CRC patients who underwent curative resection followed by adjuvant FOLFOX. Overall survival (OS) and disease-free survival (DFS) were compared between subgroups classified by methylation status, and interactions with clinico-pathological features were analyzed. Results: CIMP-high (>= 5 methylated loci) and concurrent methylation in NEUROG1 and CDKN2A (p16) were found in 5.8 and 7.9 % of patients, respectively. Although CIMP-high status was not associated with survival, concurrent methylation in NEUROG1 and CDKN2A (p16) was associated with shorter OS and DFS. Moreover, the prognostic role of the concurrent methylation was different among sex. The negative prognostic impact was only observed in male but not in female (interaction p value = 0.026 for OS and 0.011 for DFS). In male, the 5-year OS was 61.6 % in concurrent methylation (+) and 91.7 % in concurrent methylation (-) (p < 0.001) whereas it was 95.0 and 92.8 % in female, respectively (p = 0.78). Conclusions: Concurrent methylation in NEUROG1 and CDKN2A is associated with poor survival in CRC treated with adjuvant FOLFOX. Interaction analysis indicates that the prognostic role is different according to sex.
ISSN
1868-7075
Language
English
URI
https://hdl.handle.net/10371/100419
DOI
https://doi.org/10.1186/s13148-015-0106-0
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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