INTRODUCTION: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. METHODS: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. CONCLUSIONS: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.
INTRODUCTION: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. METHODS: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. CONCLUSIONS: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.
Authors: Dan Turner; Simon P L Travis; Anne M Griffiths; Frank M Ruemmele; Arie Levine; Eric I Benchimol; Marla Dubinsky; George Alex; Robert N Baldassano; Jacob C Langer; Robert Shamberger; Jeffrey S Hyams; Salvatore Cucchiara; Athos Bousvaros; Johanna C Escher; James Markowitz; David C Wilson; Gert van Assche; Richard K Russell Journal: Am J Gastroenterol Date: 2011-01-11 Impact factor: 10.864
Authors: Ilona Kryczek; Ke Wu; Ende Zhao; Shuang Wei; Linhua Vatan; Wojciech Szeliga; Emina Huang; Joel Greenson; Alfred Chang; Jacek Roliński; Piotr Radwan; Jingyuan Fang; Guobin Wang; Weiping Zou Journal: J Immunol Date: 2011-02-28 Impact factor: 5.422
Authors: B Vogelstein; E R Fearon; S R Hamilton; S E Kern; A C Preisinger; M Leppert; Y Nakamura; R White; A M Smits; J L Bos Journal: N Engl J Med Date: 1988-09-01 Impact factor: 91.245
Authors: G C Burmer; P S Rabinovitch; R C Haggitt; D A Crispin; T A Brentnall; V R Kolli; A C Stevens; C E Rubin Journal: Gastroenterology Date: 1992-11 Impact factor: 22.682