TY - JOUR
T1 - 8q24 Polymorphisms and Diabetes Mellitus Regulate Apolipoprotein A-IV in Colorectal Carcinogenesis
AU - Sugimachi, Keishi
AU - Yamaguchi, Rui
AU - Eguchi, Hidetoshi
AU - Ueda, Masami
AU - Niida, Atsushi
AU - Sakimura, Shotaro
AU - Hirata, Hidenari
AU - Uchi, Ryutaro
AU - Shinden, Yoshiaki
AU - Iguchi, Tomohiro
AU - Morita, Kazutoyo
AU - Yamamoto, Ken
AU - Miyano, Satoru
AU - Mori, Masaki
AU - Maehara, Yoshihiko
AU - Mimori, Koshi
N1 - Funding Information:
This research used the super-computing resource provided by Human Genome Center, the Institute of Medical Science, the University of Tokyo ( http://sc.hgc.jp/shirokane.html ). We thank Teikyo University School of Medicine, Tokyo, Japan; Kitazato University, Sagamihara, Japan; Northern Yokohama Hospital; Showa University, Yokohama, Japan; National Defense Medical College, Tokorozawa, Japan; Mie University, Tsu, Japan; Takano Hospital, Kumamoto, Japan; National Cancer Center, Tokyo, Japan; Tokyo Medical and Dental University, Tokyo, Japan for providing clinical samples. We thank K. Oda, M. Kasagi, S Kohno, T. Kawano, and M. Aoyagi for their technical assistance. This work was supported in part by the following Grants and foundations: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (Grant numbers 21591644, 21791295, 21791297, 215921014, and 21679006); New Energy and Industrial Technology Development Organization (NEDO) Technological Development for Chromosome Analysis; Grant of Clinical Research Foundation (2008–2010).
Publisher Copyright:
© 2016, Society of Surgical Oncology.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Background: Here, we explored the genetic interactions between diabetes and oncogenic single-nucleotide polymorphisms (SNPs) that determine colorectal cancer (CRC) morbidity. Methods: 8q24 rs6983267 polymorphism analysis and cDNA microarray were performed in 107 CRCs to identify the genes associated with diabetes and the oncogenic SNP. Then clinical significance of the gene was validated in 132 CRCs. Meta-analysis of microarray data and diabetic comorbidity was performed. Results: Of genes associated with a minor SNP allele at 8q24, diabetes, and MYC overexpression, apolipoprotein A-IV (ApoA-IV) was associated with oncogenesis and poor prognosis in CRC patients. Patients with high ApoA-IV expression showed significantly poorer prognosis by univariate and multivariate analysis. Meta-analysis revealed lipid metabolism was associated with ApoA-IV-related oncogenesis in diabetic patients. Conclusions: Changes in lipid metabolism associated with aberrant expression of ApoA-IV were risks for CRC oncogenesis.
AB - Background: Here, we explored the genetic interactions between diabetes and oncogenic single-nucleotide polymorphisms (SNPs) that determine colorectal cancer (CRC) morbidity. Methods: 8q24 rs6983267 polymorphism analysis and cDNA microarray were performed in 107 CRCs to identify the genes associated with diabetes and the oncogenic SNP. Then clinical significance of the gene was validated in 132 CRCs. Meta-analysis of microarray data and diabetic comorbidity was performed. Results: Of genes associated with a minor SNP allele at 8q24, diabetes, and MYC overexpression, apolipoprotein A-IV (ApoA-IV) was associated with oncogenesis and poor prognosis in CRC patients. Patients with high ApoA-IV expression showed significantly poorer prognosis by univariate and multivariate analysis. Meta-analysis revealed lipid metabolism was associated with ApoA-IV-related oncogenesis in diabetic patients. Conclusions: Changes in lipid metabolism associated with aberrant expression of ApoA-IV were risks for CRC oncogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84978134313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978134313&partnerID=8YFLogxK
U2 - 10.1245/s10434-016-5374-1
DO - 10.1245/s10434-016-5374-1
M3 - Article
AN - SCOPUS:84978134313
VL - 23
SP - 546
EP - 551
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
SN - 1068-9265
ER -
