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.

No abstract

No abstract

No abstract

Abstract:The essential oil obtained from the leaves of Eugenia uniflora L., Myrtaceae, which grows in the Brazilian savannah, was studied by gas chromatography mass spectrometry (GC-MS). Furanodiene (1.2%) was thermally rearranged to curzerene (85.1%) to produce a combined content of 86.3%. GC analysis carried out under mild conditions (with a constant temperature of 100 o C) showed that the furanodiene concentration was threefold greater than the curzerene concentration, i.e., the essential oil contained 64.7% furanodiene and 21.6% curzerene. Germacrene B also rearranged to γ-elemene and the concentration of both was 2.3%. Special care should be taken when conventional gas chromatography analysis is used for quantifying compounds that can rearrange at high temperatures.