Genomes and Genes
Inflammatory Biomarkers and Colorectal Cancer Risk
Principal Investigator: G Yang
Abstract: Colorectal cancer (CRC) is a major cause of cancer deaths in the United States and many other countries. Chronic inflammation has been suggested to play a major role in the pathogenesis of CRC. We propose in this application to conduct a nested case-control study within the Shanghai Women's Health Study, a large population-based prospective cohort study, to evaluate the association of CRC risk with measures of several key products of the inflammatory process and with related genetic markers of inflammation. Specifically, we will include 580 incident cases of CRC and their individually matched controls (1 to1 match for biochemical markers and 1 to 3 match for genetic markers). Urine samples collected at baseline will be measured for a major metabolite of prostaglandin E2 (PGE2) using a liquid chromatographic/mass spectrometric assay and F2-isoprostanes using the mass spectrometric method. Baseline blood samples will be measured for soluble tumor necrosis factor-a receptors, interleukin-6, and C-reactive protein. Genomic DNA will be assayed for polymorphisms in genes involved in PGE2 production (PTGS2, PTGES), metabolism (15-PGDH), and signaling (PTGER1-PTGER4). We will perform statistical analyses to evaluate the associations between these biochemical and genetic markers of inflammation and CRC risk and potential interactions of these markers. Given the large sample size, the prospective study design, the availability of comprehensive baseline survey data and biospecimens, as well as the excellent collaborative environment, we believe that this proposed study represents a unique opportunity to evaluate, vigorously and cost-efficiently, the relationship between various markers of inflammation and CRC. Overall, this study will contribute significantly to the understanding of the role of inflammation in the etiology of CRC and to the development of new strategies for the assessment of CRC risk.
Funding Period: ----------------2007 - ---------------2011-
more information: NIH RePORT
- Soy food intake and circulating levels of inflammatory markers in Chinese womenSheng Hui Wu
Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203 1738, USA
J Acad Nutr Diet 112:996-1004, 1004.e1-4. 2012..Soy and some of its constituents, such as isoflavones, have been shown to affect the inflammatory process in animal studies. The association between soy food intake and inflammatory markers has not been evaluated adequately in humans...
- Body weight, fat distribution and colorectal cancer risk: a report from cohort studies of 134255 Chinese men and womenH Li
Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Int J Obes (Lond) 37:783-9. 2013..The objective was to evaluate the association of body size and fat distribution with the risk of colorectal cancer (CRC) in Chinese men and women...
- Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancerWei Hua Jia
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, Guangzhou, China
Nat Genet 45:191-6. 2013..This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC...
- Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysisUlrike Peters
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
Gastroenterology 144:799-807.e24. 2013..Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis...
- Adiposity and fat distribution in relation to inflammation and oxidative stress in a relatively lean population of Chinese womenSheng Hui Wu
Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Dis Markers 34:279-93. 2013..This study evaluated associations of various anthropometric measures of adiposity with a panel of inflammatory and oxidative stress markers in a relatively lean population of Chinese women...
- Soy food consumption and lung cancer risk: a meta-analysis using a common measure across studiesSheng Hui Wu
Division of Epidemiology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37203 1738, USA
Nutr Cancer 65:625-32. 2013..This study suggests a borderline reduction in risk of lung cancer with daily soy protein intake in grams, and a significant inverse association in nonsmokers. ..
- Nonexercise physical activity and inflammatory and oxidative stress markers in womenSheng Hui Wu
1 Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
J Womens Health (Larchmt) 23:159-67. 2014..Leisure time exercise has been linked to lower circulating levels of inflammatory markers. Few studies have examined the association of nonexercise physical activity with markers of inflammation and oxidative stress...
- Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East AsiansBen Zhang
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN
Int J Cancer 135:948-55. 2014..This study identifies a new CRC risk variant in the SMAD7 gene, further highlighting the significant role of this gene in the etiology of CRC...
- Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer riskBen Zhang
Division of Epidemiology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Nat Genet 46:533-42. 2014..11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways. ..
- Prospective cohort study of soy food intake and colorectal cancer risk in womenGong Yang
Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203 1738, USA
Am J Clin Nutr 89:577-83. 2009..Data from epidemiologic studies linking usual soy food intake with colorectal cancer are limited and inconsistent...
- Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer riskGong Yang
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
Am J Clin Nutr 91:704-11. 2010..Glutathione S-transferases (GSTs) are involved in the metabolism and elimination of isothiocyanates; thus, genetic variations in these enzymes may affect in vivo bioavailability and the activity of isothiocyanates...
- Dietary glycemic load and risk of colorectal cancer in Chinese womenHong Lan Li
Shanghai Cancer Institute, Shanghai, China
Am J Clin Nutr 93:101-7. 2011..This association has not been prospectively evaluated in other populations...
- Green tea consumption and colorectal cancer risk: a report from the Shanghai Men's Health StudyGong Yang
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, IMPH, Nashville, TN 37203, USA
Carcinogenesis 32:1684-8. 2011..88, 95% CI: 0.78-0.99). No significant association was found among smokers (HR = 0.94, 95% CI: 0.66-1.34). This study suggests that regular consumption of green tea may reduce colorectal cancer risk among non-smokers...