Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach

H.-l. Wong; W.-P. Koh; Probst-Hensch, N. M.; Van Den Berg, D.; Yu, M. C.; Ingles, S. A.
August 2008
Gut;Aug2008, Vol. 57 Issue 8, p1090
Academic Journal
Rationale: Insulin-like growth factor-1 (IGF1) has been proposed to mediate the obesity-related carcinogenic effects of `Western lifestyle. While genetic factors explain at least half of inter-individual IGF1 variation, the IGF1 polymorphisms hypothesised to underlie the variation in cancer incidence rates remain ill-defined. Methods: We used a comparative genomics approach to identify putative regulatory polymorphisms in the IGE1 promoter region within a rapidly westernising population, the Singapore Chinese. Association of IGF1 genotype with colorectal cancer risk was assessed among 298 colorectal cancer cases and 1142 controls nested within the Singapore Chinese Health Study. Results: We identified a common (minor allele frequency = 0.36) single-nucleotide polymorphism (SNP), IGF1-2995 C/A, within a consensus domain for an octamer binding factor (Oct1/Oct2) transcription factor binding site. Possession of one or two copies of the minor allele (genotypes AA and CA) conferred an approximate 40% decrease in risk in comparison to genotype CC (odds ratio, 0.59; 95% confidence interval, 0.45 to 0.77). This association was stronger for colon cancer than for rectal cancer (pheterogeneity<0.001) and for those who were physically active versus inactive (pinteraction = 0.05). Models including other previously identified promoter polymorphisms did not provide a better prediction of colorectal cancer risk. Conclusions: Our results support the hypotheses that IGF1 plays a role in colonic carcinogenesis and that genetically inherited variation in IGF1 expression influences risk of colorectal cancer.


Related Articles

  • Association of genetic variants in tachykinins pathway genes with colorectal cancer risk. Yu, Yunxian; Pan, Yifeng; Jin, Mingjuan; Zhang, Mingwu; Zhang, Shanchun; Li, Qilong; Jiang, Xia; Liu, Hui; Guo, Jing; Liu, He; Chen, Kun // International Journal of Colorectal Disease;Nov2012, Vol. 27 Issue 11, p1429 

    Purpose: This study aims to explore the associations of polymorphisms in tachykinin, precursor 1 ( TAC1), tachykinin receptor 1 (T ACR1), and tachykinin receptor 2 ( TACR2) genes and their interactions with the risk of colorectal cancer (CRC) among Chinese population. Methods: A population-based...

  • Association of p73 G4C14-to-A4T14 (GC/AT) polymorphism with breast cancer survival. Bin Dong; Jiyou Li; Yuntao Xie // Carcinogenesis;Feb2007, Vol. 28 Issue 2, p372 

    p73 gene shares structural and functional similarities to p53, and plays an important role in modulating cell-cycle arrest and apoptosis. A common non-coding polymorphism of exon 2 of the p73 gene (designated as GC/AT) may affect gene expression, thus, it may lead to functional significance. The...

  • The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population. Christensen, Lise Lotte; Madsen, Bo E.; Wikman, Friedrik P.; Wiuf, Carsten; Koed, Karen; Tjønneland, Anne; Olsen, Anja; Syvänen, Ann-Christine; Andersen, Claus L.; Ørntoft, Torben F. // BMC Medical Genetics;2008, Vol. 9, Special section p1 

    Background: Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense,...

  • COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer. Tomlinson, I. P. M.; Dunlop, M.; Campbell, H.; Zanke, B.; Gallinger, S.; Hudson, T.; Koessler, T.; Pharoah, P. D.; Niittymäkix, I.; Tuupanenx, S.; Aaltonen, L. A.; Hemminki, K.; Lindblom, A.; Försti, A.; Sieber, O.; Lipton, L.; van Wezel, T.; Morreau, H.; Wijnen, J. T.; Devilee, P. // British Journal of Cancer;1/19/2010, Vol. 102 Issue 2, p447 

    It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and...

  • Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker. Ravegnini, Gloria; Moraga, Juan Manuel Zolezzi; Maffei, Francesca; Musti, Muriel; Zenesini, Corrado; Simeon, Vittorio; Sammarini, Giulia; Festi, Davide; Hrelia, Patrizia; Angelini, Sabrina // International Journal of Molecular Sciences;2015, Vol. 16 Issue 12, p28486 

    One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects' positive fecal occult blood test (FOBT). In order to add new...

  • Complete deletion of Apc results in severe polyposis in mice. Cheung, A. F.; Carter, A. M.; Kostova, K. K.; Woodruff, J. F.; Crowley, D.; Bronson, R. T.; Haigis, K. M.; Jacks, T. // Oncogene;3/25/2010, Vol. 29 Issue 12, p1857 

    The adenomatous polyposis coli (APC) gene product is mutated in the vast majority of human colorectal cancers. APC negatively regulates the WNT pathway by aiding in the degradation of β-catenin, which is the transcription factor activated downstream of WNT signaling. APC mutations result in...

  • Polymorphisms in methionine synthase (A2756G) and cystathionine β-synthase (844ins68) and susceptibility to carcinomas of the upper gastrointestinal tract. Ott, N.; Geddert, H.; Sarbia, M. // Journal of Cancer Research & Clinical Oncology;Mar2008, Vol. 134 Issue 3, p405 

    Folate deficiency is considered to increase the risk for the development of malignant tumors such as prostate and colorectal cancer. Methionine synthase (MTR) and cystathionine ß-synthase (CBS) are enzymes that play a central role in folate metabolism, thereby affecting DNA methylation and...

  • Relationship between growth hormone 1 genetic polymorphism and susceptibility to colorectal cancer. Chang-Ming Gao; Jian-Ping Gong; Jian-Zhong Wu; Hai-Xia Cao; Jian-Hua Ding; Jian-Nong Zhou; Yan-Ting Liu; Su-Ping Li; Jia Cao; Matsuo, Keitaro; Takezaki, Toshiro; Tajima, Kazuo // Journal of Human Genetics;Mar2010, Vol. 55 Issue 3, p163 

    The aim of this study was to evaluate the relationship between smoking, alcohol drinking and genetic polymorphism of the growth hormone 1 gene (GH1) T1663A with reference to colorectal cancer. We conducted a case–control study with 315 cases of colorectal cancer and 438 population-based...

  • A genome-wide scan of 10 000 gene-centric variants and colorectal cancer risk. Webb, Emily; Broderick, Peter; Lubbe, Steven; Chandler, Ian; Tomlinson, Ian; Houlston, Richard S. // European Journal of Human Genetics;Nov2009, Vol. 17 Issue 11, p1507 

    Genome scans based on gene-centric single nucleotide polymorphisms (SNPs) have been proposed as an efficient approach to identify disease-causing variants that is complementary to scans based on tagging SNPs. Adopting this approach to identify low-penetrance susceptibility alleles for colorectal...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics