IL-1RN VNTR polymorphism and genetic susceptibility to cervical cancer in Portugal Hugo Sousa • Alexandra M. Santos • Raquel Catarino • Daniela Pinto • Jose ´ Moutinho • Paulo Canedo • Jose ´ Carlos Machado • Rui Medeiros Received: 24 November 2011 / Accepted: 1 October 2012 / Published online: 10 October 2012 Ó Springer Science+Business Media Dordrecht 2012 Abstract Human Papillomavirus infection is considered as the main etiological factor of cervical cancer (ICC), although, the role of host genetic factors in ICC suscepti- bility has been increasing. Immunological response is crucial for the prevention of viral associated diseases. Interleukin 1 receptor antagonist (IL-1RN) is considered to be an important regulator of host immunity and several studies have shown a potential role of a 86 bp VNTR polymorphism within intron 2 of the IL-1RN gene in host immune response variability. We investigated the role of this polymorphism in cervical cancer development in Portugal with a case–control study developed with peripheral blood samples from 196 healthy women and 340 women with cervical lesions from the Northern Region of Portugal. We observed that IL-1RN Allele 2 homozygosis was significantly higher in cases than in controls. In fact, IL-1RN A2*A2 homozygous revealed to be associated with an increased risk of HSIL ? ICC (OR = 1.90; 95 % IC 1.13–3.21; p = 0.015). Furthermore, we also observed that median age of onset of HSIL ? ICC was significantly different (46.0 vs 52.0) in IL-1RN A2*A2 homozygous comparing to non-A2*A2 (p = 0.028). Our results indi- cated that IL-1RN A2 allele is associated with an increased susceptibility to cervical cancer development, probably by increasing predisposition to shorter immune responses. Keywords Cervical cancer Á Human Papillomavirus (HPV) Á Genetic polymorphism Á Interleukin 1 Á IL-1RN Introduction Cervical cancer is the second most common cancer in women with almost 500,000 new cases each year and over 260,000 deaths [1, 2]. Moreover, it is estimated that over 1 million women worldwide have cervical cancer and the majority of them have not yet been diagnosed [2]. In the early 90’s persistent infection by the oncogenic types of the Human Papillomavirus (HPV) was established as the etiological factor for the development of cervical cancer [3–8]. Over time, several studies have been focusing on the role of risk factors that influence either the acqui- sition of persistent HPV infection or by contributing for the H. Sousa (&) Á A. M. Santos Á R. Catarino Á D. Pinto Á R. Medeiros Grupo de Oncologia Molecular—CI, Laborato ´rios 4° Piso, Instituto Portugue ˆs de Oncologia do Porto FG, EPE, Rua Dr. Anto ´nio Bernardino Almeida, 4200-072 Porto, Portugal e-mail: hugomls@gmail.com H. Sousa Á R. Medeiros Servic ¸o de Virologia, Laborato ´rios 48 Piso, Instituto Portugue ˆs de Oncologia do Porto FG, EPE, Rua Dr. Anto ´nio Bernardino Almeida, 4200-072 Porto, Portugal J. Moutinho Servic ¸o de Ginecologia, Instituto Portugue ˆs de Oncologia do Porto FG, EPE, Rua Dr. Anto ´nio Bernardino Almeida, 4200-072 Porto, Portugal P. Canedo Á J. C. Machado IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal J. C. Machado Faculty of Medicine of University of Porto, Al. Prof. Herna ˆni Monteiro, 4200-319 Porto, Portugal R. Medeiros ICBAS—Abel Salazar Institute for the Biomedical Sciences of University of Porto, Rua de Jorge Viterbo Ferreira n.8 228, 4050-313 Porto, Portugal 123 Mol Biol Rep (2012) 39:10837–10842 DOI 10.1007/s11033-012-1979-z