Nádia Calvo Martins Okuyama1, Fernando Cezar-Dos-Santos1, Kleber Paiva Trugilo1, Aline Esposito1, Roberta Losi Guembarovski2, José d'Oliveira Couto-Filho3, Maria Angelica Ehara Watanabe4, Karen Brajão de Oliveira5. 1. Laboratory of Molecular Genetics and Immunology, Department of Pathological Science, Londrina State University, Londrina, PR, Brazil. 2. Laboratory of Mutagenesis and Oncogenetics, Department of Biological Sciences, Londrina State University, Londrina, PR, Brazil. 3. Cancer Hospital of Londrina, Londrina, PR, Brazil. 4. Laboratory of Study and Application of DNA Polymorphism, Department of Pathological Science, Londrina State University, Londrina, PR, Brazil. 5. Laboratory of Molecular Genetics and Immunology, Department of Pathological Science, Londrina State University, Londrina, PR, Brazil. karen.brajao@uel.br.
Abstract
PURPOSE: Every year, more than half a million women are diagnosed with cervical cancer (CC). Individual factors may contribute to the cervical cancer development, such as immunogenetic variation. CXCL12/CXCR4 axis is involved in tumor progression and aggressiveness. In the present study, we aimed to investigate a possible association between two single-nucleotide variants (CXCL12 rs1801157 and CXCR4 rs2228014) with HPV infection and cervical cancer development. METHODS: PCR technique was used to test HPV positivity in 424 women, in which the allelic frequency of CXCL12 rs1801157 and CXCR4 rs2228014 was also assessed by PCR-restriction fragment length polymorphism. RESULTS: CXCL12 rs1801157 was associated with HPV infection in the allelic distribution as well in the codominant, dominant and recessive genetic models; as well with squamous intraepithelial lesions (SIL) and CC in the codominant and dominant models. CXCR4 rs2228014 was associated to HPV infection in the codominant model and allelic distribution; as well with SIL/CC in the codominant, dominant and allelic models. Independent associations were found for CXCL12 AA genotype and HPV infection, SIL and CC development, as well as, CXCR4 allele T and HPV infection and CC. The variants interaction analysis demonstrated that the presence of both polymorphisms increases the susceptibility of HPV infection in 10.1 times, SIL (2 times) and CC development in 4.2 times. CONCLUSIONS: This is the first study demonstrating that the interaction of CXCL12 and CXCR4 variants contributes to the increased susceptibility of HPV infection, squamous intraepithelial lesions and cervical cancer development.
PURPOSE: Every year, more than half a million women are diagnosed with cervical cancer (CC). Individual factors may contribute to the cervical cancer development, such as immunogenetic variation. CXCL12/CXCR4 axis is involved in tumor progression and aggressiveness. In the present study, we aimed to investigate a possible association between two single-nucleotide variants (CXCL12 rs1801157 and CXCR4 rs2228014) with HPV infection and cervical cancer development. METHODS: PCR technique was used to test HPV positivity in 424 women, in which the allelic frequency of CXCL12 rs1801157 and CXCR4 rs2228014 was also assessed by PCR-restriction fragment length polymorphism. RESULTS: CXCL12 rs1801157 was associated with HPV infection in the allelic distribution as well in the codominant, dominant and recessive genetic models; as well with squamous intraepithelial lesions (SIL) and CC in the codominant and dominant models. CXCR4 rs2228014 was associated to HPV infection in the codominant model and allelic distribution; as well with SIL/CC in the codominant, dominant and allelic models. Independent associations were found for CXCL12 AA genotype and HPV infection, SIL and CC development, as well as, CXCR4 allele T and HPV infection and CC. The variants interaction analysis demonstrated that the presence of both polymorphisms increases the susceptibility of HPV infection in 10.1 times, SIL (2 times) and CC development in 4.2 times. CONCLUSIONS: This is the first study demonstrating that the interaction of CXCL12 and CXCR4 variants contributes to the increased susceptibility of HPV infection, squamous intraepithelial lesions and cervical cancer development.
Authors: Carelia García-Moruja; Juan M Alonso-Lobo; Patricia Rueda; Carmen Torres; Nuria González; Mercedes Bermejo; Francisco Luque; Fernando Arenzana-Seisdedos; José Alcamí; Antonio Caruz Journal: J Mol Biol Date: 2005-04-22 Impact factor: 5.469
Authors: Karen Brajão de Oliveira; Roberta Losi Guembarovski; Julie Massayo Maeda Oda; Mário Sérgio Mantovani; Clisia Mara Carrera; Edna Maria Vissoci Reiche; Julio Cesar Voltarelli; Ana Cristina da Silva do Amaral Herrera; Maria Angelica Ehara Watanabe Journal: Cytokine Date: 2011-05-17 Impact factor: 3.861
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702