New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer

New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer

Author Guzman, Valeska Barcelos Autor UNIFESP Google Scholar
Yambartsev, Anatoly Google Scholar
Goncalves-Primo, Amador Autor UNIFESP Google Scholar
Silva, Ismael Dale Cotrim Guerreiro da Autor UNIFESP Google Scholar
Carvalho, Carmen R. N. Autor UNIFESP Google Scholar
Ribalta, Julisa Chamorro Lascasas Autor UNIFESP Google Scholar
Goulart, Luiz Ricardo Google Scholar
Shulzhenko, Natalia Autor UNIFESP Google Scholar
Gerbase-DeLima, Maria Google Scholar
Morgun, Andrey Autor UNIFESP Google Scholar
Institution NIAID
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Universidade Federal de Uberlândia (UFU)
Abstract Cervical cancer is a complex disease with multiple environmental and genetic determinants. in this study, we sought an association between polymorphisms in immune response genes and cervical cancer using both single-locus and multi-locus analysis approaches. A total of 14 single nucleotide polymorphisms (SNPs) distributed in CD28 , CTLA4 , ICOS , PDCD1 , FAS , TNFA , IL6 , IFNG , TGFB1 and IL10 genes were determined in patients and healthy individuals from three independent case/control sets. the first two sets comprised White individuals (one group with 82 cases and 85 controls, the other with 83 cases and 85 controls) and the third was constituted by non-white individuals (64 cases and 75 controls). the multi-locus analysis revealed higher frequencies in cancer patients of three three-genotype combinations [CD28 +17(TT)/ IFNG +874(AA)/ TNFA -308(GG), CD28 +17(TT)/ IFN+ 847(AA)/ PDCD1 +7785(CT), and CD28 +17(TT)/ IFNG +874(AA)/ ICOS +1564(TT)] (P < 0.01, Monte Carlo simulation). We hypothesized that this two-genotype [CD28 (TT) and IFNG (AA)] combination could have a major contribution to the observed association. To address this question, we analyzed the frequency of the CD28 (TT), IFNG (AA) genotype combination in the three groups combined, and observed its increase in patients (P = 0.0011 by Fisher's exact test). the contribution of a third polymorphism did not reach statistical significance (P = 0.1). Further analysis suggested that gene-gene interaction between CD28 and IFNG might contribute to susceptibility to cervical cancer. Our results showed an epistatic effect between CD28 and IFNG genes in susceptibility to cervical cancer, a finding that might be relevant for a better understanding of the disease pathogenesis. in addition, the novel analytical approach herein proposed might be useful for increasing the statistical power of future genome-wide multi-locus studies.
Language English
Date 2008-06-15
Published in Human Molecular Genetics. Oxford: Oxford Univ Press, v. 17, n. 12, p. 1838-1844, 2008.
ISSN 0964-6906 (Sherpa/Romeo, impact factor)
Publisher Oxford Univ Press
Extent 1838-1844
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000256275600015

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