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

Nimptsch, Katharina; Aleksandrova, Krasimira; Boeing, Heiner; Janke, Juergen; Lee, Young-Ae; Jenab, Mazda; Kong, So Yeon; Tsilidis, Konstantinos K.; Weiderpass, Elisabete and Bueno-de-Mesquita, H. B(As), et al. (2015) In International Journal of Cancer 137(4). p.911-920
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 prediagnostic 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% confidence interval) of colorectal... (More)
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 prediagnostic 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% confidence interval) of colorectal cancer per 40 mg/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, 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, five 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 interindividual 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 mg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 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. (Less)
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publication status
published
subject
keywords
fetuin-A, AHSG, colorectal cancer
in
International Journal of Cancer
volume
137
issue
4
pages
911 - 920
publisher
John Wiley & Sons
external identifiers
  • wos:000356428400017
  • scopus:84931566002
ISSN
0020-7136
DOI
10.1002/ijc.29448
language
English
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yes
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795a618c-eedc-4f33-b75c-5a8fa30c6fea (old id 7596602)
date added to LUP
2015-08-03 10:10:03
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2017-05-21 03:08:47
@article{795a618c-eedc-4f33-b75c-5a8fa30c6fea,
  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 prediagnostic 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% confidence interval) of colorectal cancer per 40 mg/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, 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, five 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 interindividual 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 mg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 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.},
  author       = {Nimptsch, Katharina and Aleksandrova, Krasimira and Boeing, Heiner and Janke, Juergen and Lee, Young-Ae and Jenab, Mazda and Kong, So Yeon and Tsilidis, Konstantinos K. and Weiderpass, Elisabete and Bueno-de-Mesquita, H. B(As) and Siersema, Peter D. and Jansen, Eugene H. J. M. and Trichopoulou, Antonia and Tjonneland, Anne and Olsen, Anja and Wu, Chunsen and Overvad, Kim and Boutron-Ruault, Marie-Christine and Racine, Antoine and Freisling, Heinz and Katzke, Verena and Kaaks, Rudolf and Lagiou, Pagona and Trichopoulos, Dimitrios and Severi, Gianluca and Naccarati, Alessio and Mattiello, Amalia and Palli, Domenico and Grioni, Sara and Tumino, Rosario and Peeters, Petra H. and Ljuslinder, Ingrid and Nystrom, Hanna and Brändstedt, Jenny and Sanchez, Maria-Jose and Gurrea, Aurelio Barricarte and Bonet, Catalina Bonet and Chirlaque, Maria-Dolores and Dorronsoro, Miren and Quiros, Jose Ramon and Travis, Ruth C. and Khaw, Kay-Tee and Wareham, Nick and Riboli, Elio and Gunter, Marc J. and Pischon, Tobias},
  issn         = {0020-7136},
  keyword      = {fetuin-A,AHSG,colorectal cancer},
  language     = {eng},
  number       = {4},
  pages        = {911--920},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer},
  url          = {http://dx.doi.org/10.1002/ijc.29448},
  volume       = {137},
  year         = {2015},
}