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

Katharina Nimptsch, Krasimira Aleksandrova, Heiner Boeing, Juergen Janke, Young-Ae Lee, Mazda Jenab, So Yeon Kong, Konstantinos K. Tsilidis, Elisabete Weiderpass, H. B(As) Bueno-de-Mesquita, Peter D. Siersema, Eugene H. J. M. Jansen, Antonia Trichopoulou, Anne Tjonneland, Anja Olsen, Chunsen Wu, Kim Overvad, Marie-Christine Boutron-Ruault, Antoine Racine, Heinz FreislingVerena Katzke, Rudolf Kaaks, Pagona Lagiou, Dimitrios Trichopoulos, Gianluca Severi, Alessio Naccarati, Amalia Mattiello, Domenico Palli, Sara Grioni, Rosario Tumino, Petra H. Peeters, Ingrid Ljuslinder, Hanna Nystrom, Jenny Brändstedt, Maria-Jose Sanchez, Aurelio Barricarte Gurrea, Catalina Bonet Bonet, Maria-Dolores Chirlaque, Miren Dorronsoro, Jose Ramon Quiros, Ruth C. Travis, Kay-Tee Khaw, Nick Wareham, Elio Riboli, Marc J. Gunter, Tobias Pischon

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

14 Citeringar (SciVal)

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)911-920
TidskriftInternational Journal of Cancer
Volym137
Utgåva4
DOI
StatusPublished - 2015

Bibliografisk information

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Pathology, (Lund) (013030000)

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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