Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer
Nimptsch, Katharina; Aleksandrova, Krasimira; Boeing, Heiner; Janke, Jürgen; Lee, Young Ae; Jenab, Mazda; Kong, So Yeon; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Bueno-De-Mesquita, H. Bas; Siersema, Peter D.; Jansen, Eugène H J M; Trichopoulou, Antonia; Tjønneland, Anne; Olsen, Anja; Wu, Chunsen; Overvad, Kim; Boutron-Ruault, Marie Christine; Racine, Antoine; Freisling, Heinz; Katzke, Verena; Kaaks, Rudolf; Lagiou, Pagona; Trichopoulos, Dimitrios; Severi, Gianluca; Naccarati, Alessio; Mattiello, Amalia; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Peeters, Petra H.; Ljuslinder, Ingrid; Nyström, Hanna; Brändstedt, Jenny; Sánchez, María José; Gurrea, Aurelio Barricarte; Bonet, Catalina Bonet; Chirlaque, María Dolores; Dorronsoro, Miren; Quirõs, José Ramõn; Travis, Ruth C.; Khaw, Kay Tee; Wareham, Nick; Riboli, Elio; Gunter, Marc J.; Pischon, Tobias
(2015) International Journal of Cancer, volume 137, issue 4, pp. 911 - 920
(Article)
Abstract
Fetuin-A, also referred to as α2-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
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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 μg/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 μg/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. What's new? Fetuin-A is a liver protein associated with insulin resistance, but with no defined role yet in colorectal cancer. In this prospective study, the authors uncover a modest linear association between fetuin-A levels and higher risk of colorectal cancer, but this was only observed in male participants. In addition, no association was observed between fetuin-A variants and colorectal cancer risk in a Mendelian randomization analysis, arguing against a direct role of fetuin-A in colorectal carcinogenesis.
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Keywords: AHSG, colorectal cancer, fetuin-A, Cancer Research, Oncology, General Medicine
ISSN: 0020-7136
Publisher: John Wiley & Sons Inc.
(Peer reviewed)