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Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

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Item Type:Article
Title:Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer
Creators Name:Nimptsch, K. and Aleksandrova, K. and Boeing, H. and Janke, J. and Lee, Y.A. and Jenab, M. and Yeon Kong, S. and Tsilidis, K.K. and Weiderpass, E. and Bueno-De-Mesquita, B.H. and Siersema, P.D. and Jansen, E.H.J.M. and Trichopoulou, A. and Tjønneland, A. and Olsen, A. and Wu, C. and Overvad, K. and Boutron-Ruault, M.C. and Racine, A. and Freisling, H. and Katzke, V. and Kaaks, R. and Lagiou, P. and Trichopoulos, D. and Severi, G. and Naccarati, A. and Mattiello, A. and Palli, D. and Grioni, S. and Tumino, R. and Peeters, P.H. and Ljuslinder, I. and Nyström, H. and Brändstedt, J. and Sánchez, M.J. and Barricarte Gurrea, A. and Bonet Bonet, C. and Chirlaque, M.D. and Dorronsoro, M. and Quirós, J.R. and Travis, R.C. and Khaw, K.T. and Wareham, N. and Riboli, E. and Gunter, M.J. and Pischon, T.
Abstract:Fetuin-A, also referred to as {alpha}2-Heremans-Schmid glycoprotein (AHSG) is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer, however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in pre-diagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders the estimated relative risk (95% CI) of colorectal cancer per 40 {my}g/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02, 1.24) overall, 1.21 (1.05, 1.39) in men and 1.06 (0.93, 1.22) in women, 1.13 (1.00, 1.27) for colon cancer and 1.12 (0.94, 1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, 5 tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the inter-individual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 {my}g/mL genetically determined higher fetuin-A was 0.98, 95% CI 0.73, 1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer, but suggest that fetuin-A may not be causally related to colorectal cancer development.
Keywords:Fetuin-A, AHSG, Colorectal Cancer
Source:International Journal of Cancer
ISSN:0020-7136
Publisher:Wiley-Blackwell (Switzerland)
Volume:137
Number:4
Page Range:911-920
Date:15 August 2015
Official Publication:https://doi.org/10.1002/ijc.29448
PubMed:View item in PubMed

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