Meta and pooled analyses ofFGFR4 Gly388Arg polymorphism as a cancer prognostic factor

Frullanti, Elisa^a; Berking, Carola^b; Harbeck, Nadia^c; Jézéquel, Pascal^e; Haugen, Aage^f; Mawrin, Christian^d; Parise, Orlando Jr^g; Sasaki, Hidefumi^h; Tsuchiya, Norihikoⁱ; Dragani, Tommaso A.^a

Author Information

^aDepartment of Experimental Oncology and Laboratories, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy

^bDepartment of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich

^cFrauenklinik der Technischen Universitaet Muenchen, Munich

^dDepartment of Neuropathology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

^eUnité Mixte de Génomique du Cancer, Hôpital Laënnec, Nantes, Saint Herblain Cedex, France

^fSection for Toxicology, National Institute of Occupational Health, Oslo, Norway

^gLaboratory of Molecular Genetics, Head and Neck Surgery of the Sirio Libanes Hospital, Sao Paulo, Brazil

^hDepartment of Surgery II, Nagoya City University Medical School, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya

ⁱDepartment of Urology, Akita University School of Medicine, Akita, Japan

Correspondence to Tommaso A. Dragani, PhD, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy Tel: +39 0223902642; fax: +39 0223902764; e-mail:[email protected]

Present address: Nadia Harbeck, Breast Center, University of Cologne, Cologne, Germany

Received September 22, 2010

Accepted February 7, 2011

European Journal of Cancer Prevention20(4):p 340-347, July 2011. |DOI:10.1097/CEJ.0b013e3283457274

Abstract

Fibroblast growth factor receptor 4 (FGFR4) contains a Gly388Arg functional polymorphism (rs351855) that has shown contrasting results in association studies. In this study, we assessed the association between theFGFR4 Gly388Arg polymorphism and cancer prognosis. Meta-analysis and pooled analysis of 6817 and 2537 cancer cases, respectively, were carried out by nodal status and overall survival. The study included the following types of cancer: brain, breast, colorectal, head and neck, larynx, lung, melanoma, prostate, sarcomas. A statistically significant association between the Arg388Arg genotype and nodal involvement was found in the meta-analysis (odds ratio=1.33, 95% confidence interval 1.01–1.74). In the pooled analysis, the Arg388 allele carriers showed an increased hazard of poor overall survival compared with homozygous carriers of the common Gly388 allele, even after adjusting for nodal status (hazard ratio=1.21, 95% confidence interval 1.05–1.40). These results provide evidence of a role for theFGFR4 Gly388Arg polymorphism in modulating patients' outcome in different types of cancer, thus offering to clinicians a new marker to predict predisposition to poor survival in cancer patients.