No Association of Insulin-like Growth Factor Gene Polymorphisms with Survival in Patients with Colorectal Cancer
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose Insulin-like growth factors (IGF) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with colorectal cancer. Materials and Methods Four hundred and two consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 8 polymorphisms of IGF genes determined using a real-time polymerase chain reaction genotyping assay. Results Pathologic stages after surgery were as follows: stage 0/I (n=85, 21.1%), stage II (n=147,36.6%), stage III (n=145, 36.1%), and stage IV (n=25, 6.2%). Multivariate survival analysis including stage, age, site of disease, and carcinoembryonic antigen level showed that the progressionfree survival for patients with the IGF2 +1280 GG genotype was slightly better than for the patients with the combined IGF2 +1280 AA and AG genotype (p=0.056), although there was no significant difference in the overall survival. However, the other polymorphisms were not associated with survival. Conclusion None of the 8 IGF1 or IGF2 gene polymorphisms investigated in this study were found to be independent prognostic markers for Korean patients with surgically resected colorectal cancer.
Abstract
Purpose Insulin-like growth factors (IGF) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with colorectal cancer. Materials and Methods Four hundred and two consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 8 polymorphisms of IGF genes determined using a real-time polymerase chain reaction genotyping assay. Results Pathologic stages after surgery were as follows: stage 0/I (n=85, 21.1%), stage II (n=147,36.6%), stage III (n=145, 36.1%), and stage IV (n=25, 6.2%). Multivariate survival analysis including stage, age, site of disease, and carcinoembryonic antigen level showed that the progressionfree survival for patients with the IGF2 +1280 GG genotype was slightly better than for the patients with the combined IGF2 +1280 AA and AG genotype (p=0.056), although there was no significant difference in the overall survival. However, the other polymorphisms were not associated with survival. Conclusion None of the 8 IGF1 or IGF2 gene polymorphisms investigated in this study were found to be independent prognostic markers for Korean patients with surgically resected colorectal cancer.
참고문헌 (23)
- Popat S, "Systematic review of microsatellite instability and colorectal cancer prognosis", J Clin Oncol, 23, pp.609~618 (2005)
- Fürstenberger G, "Insulin-like growth factors and cancer", Lancet Oncol, 3, pp.298~302 (2002)
- Werner H, "New concepts in regulation and function of the insulin-like growth factors: implications for understanding normal growth and neoplasia", Cell Mol Life Sci, 57, pp.932~942 (2000)
- Giovannucci E, "Insulin, insulin-like growth factors and colon cancer: a review of the evidence", J Nutr, 131(11), pp.3109S~3120S (2001)
- Kaaks R, "Nutrition, energy balance and colon cancer risk: the role of insulin and insulin-like growth factor-I", IARC Sci Publ, 156, pp.289~293 (2002)
- Pollak MN, "Insulin-like growth factors and neoplasia", Nat Rev Cancer, 4, pp.505~518 (2004)
- Sandhu MS, "Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer", J Natl Cancer Inst, 94, pp.972~980 (2002)
- Al-Zahrani A, "IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer", Hum Mol Genet, 15, pp.1~10 (2006)
- Wong HL, "Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach", Gut, 57, pp.1090~1096 (2008)
- Zecevic M, "IGF1 gene polymorphism and risk for hereditary nonpolyposis colorectal cancer", J Natl Cancer Inst, 98, pp.139~143 (2006)
- Suzuki H, "Effect of insulin-like growth factor gene polymorphisms alone or in interaction with diabetes on the risk of pancreatic cancer", Cancer Epidemiol Biomarkers Prev, 17, pp.3467~3473 (2008)
- Hamilton SR, "World Health Organization classification of tumours, in Pathology and genetics of tumours of the digestive system" (2000), IARC Press
- Greene FL, "AJCC cancer staging manual" (2002), Springer-Verlag
- Tricoli JV, "Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas", Cancer Res, 46(12), pp.6169~6173 (1986)
- Wu Y, "Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis", Cancer Res, 62, pp.1030~1035 (2002)
- Björndahl M, "Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo", Proc Natl Acad Sci U S A, 102, pp.15593~15598 (2005)
- Cheng I, "Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort", J Natl Cancer Inst, 98, pp.123~134 (2006)
- Ma J, "Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3", J Natl Cancer Inst, 91, pp.620~625 (1999)
- Canzian F, "Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study", Br J Cancer, 94, pp.299~307 (2006)
- Lai MT, "Glutathione S-transferase M1 gene but not insulin-like growth factor-2 gene or epidermal growth factor gene is associated with prostate cancer", Urol Oncol, 23, pp.225~229 (2005)
- Kim YJ, "IGF2 polymorphisms are associated with hepatitis B virus clearance and hepatocellular carcinoma", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 346, pp.38~44 (2006), ACADEMIC PRESS INC ELSEVIER SCIENCE
- Tsuchiya N, "Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer", J Clin Oncol, 24, pp.1982~1989 (2006)
- Patel AV, "IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3)", PLoS One, 3, pp.e2578~ (2008)