Background-Nasal polyps influence the burden of aspirin exacerbated respiratory disease (AERD) by contributing to eicosanoid production. AERD is diagnosed through graded aspirin challenges. It is not known how sinus surgery affects aspirin challenge outcomes.Objective-To investigate the effects of endoscopic sinus surgery (ESS) on aspirin-induced reaction severity and on the levels of eicosanoids associated with these reactions.Methods-Twenty-eight AERD patients were challenged with aspirin before and 3-4 weeks after ESS. Respiratory parameters and plasma and urine levels of eicosanoids were compared before and after challenges.Results-Before ESS, AERD diagnosis was confirmed in all study patients by aspirin challenges that resulted in hypersensitivity reactions. After ESS, reactions to aspirin were less severe in all patients and twelve out of twenty-eight patients (43%, p<0.001) had no detectable reaction. A lack of clinical reaction to aspirin was associated with lower peripheral blood eosinophilia [0.1 K/μL

Genome-Wide Association Studies have identified several loci associated with breast cancer (BC) in populations of different ethnic origins. One of the strongest associations was found in the FGFR2 gene, and MAP3K1 has been proposed as a low-penetrance BC risk factor. In this study, we evaluated the associations among FGFR2 SNPs rs2981582, rs2420946, and rs1219648; and MAP3K1 rs889312, with BC risk in 351 BRCA1/2-negative Chilean BC cases and 802 controls. All the SNPs studied were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC, in a dose-dependent manner. Subjects with 3 risk alleles were at a significantly increased risk of BC compared with subjects with 0-2 risk alleles, in both familial BC and early-onset non-familial BC (OR = 1.47, 95 % CI 1.04-2.07, P = 0.026 and OR = 2.04 95 % CI 1.32-3.24, P < 0.001, respectively). In the haplotype analysis, the FGFR2 rs2981582 T / rs2420946 T / rs1219648 G haplotype (ht2) was associated with a significantly increased BC risk compared with the rs2981582 C / rs2420946 C / rs1219648 A haplotype in familial BC and in non-familial early-onset BC (OR = 1.32, 95 % CI 1.06-1.65, P = 0.012; OR = 1.46, 95 % CI 1.11-1.91, P = 0.004, respectively). When the FGFR2 ht2 and MAP3K1 rs889312 were evaluated as risk alleles, the risk of BC increased in a dose-dependent manner as the number of risk alleles increased (P trend <0.0001), indicating an additive effect. Nevertheless, there is no evidence of an interaction between FGFR2 ht2 and the MAP3K1 rs889312 C allele. These findings suggest that genetic variants in the FGFR2 and MAP3K1 genes may contribute to genetic susceptibility to BC.

Recent Genome-Wide Association Studies have identified several single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) among women of Asian, European, and African-American ancestry. Nevertheless, the contribution of these variants in the South American population is unknown. Furthermore, there is little information about the effect of these risk alleles in women with early BC diagnosis. In the present study, we evaluated the association between rs3803662 (TOX3, also known as TNRC9), rs13387042 (2q35), and rs13281615 (8q24) with BC risk in 344 Chilean BRCA1/2-negative BC cases and in 801 controls. Two SNPs, rs3803662 and rs13387042, were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC. The risk of BC increased in a dose-dependent manner with the number of risk alleles (P-trend < 0.0001 and 0.0091, respectively). The odds ratios for BC in familial BC and in early-onset non-familial BC were 3.76 (95%CI 1.02-13.84, P = 0.046) and 8.0 (95%CI 2.20-29.04, P = 0.002), respectively, for the maximum versus minimum number of risk alleles. These results indicate an additive effect of the TOX3 rs3803662 and 2q35 rs13387042 alleles for BC risk. We also evaluated the interaction between rs3803662 and rs13387042 SNPs. We observed an additive interaction only in non-familial early-onset BC cases (AP = 0.72 (0.28-1.16), P = 0.001). No significant association was observed for rs13281615 (8q24) with BC risk in women from the Chilean population. The strongly increased risk associated with the combination of low-penetrance risk alleles supports the polygenic inheritance model of BC.

Background Aspirin desensitization and treatment benefits most patients with aspirin‐exacerbated respiratory disease (AERD), although some patients fail therapy. Our objective was to assess whether recent endoscopic sinus surgery (ESS) improved aspirin treatment outcomes in AERD patients who initially failed aspirin therapy. Methods Outcomes of aspirin desensitization and treatment in AERD patients prospectively enrolled were assessed preoperatively and at 4, 12, and 24 weeks after ESS by determining changes in Asthma Control Test (ACT) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and respiratory function. Biomarkers, including fractional excretion of nitric oxide (FeNO), spirometry, nasal inspiratory peak flow (NPF), immunoglobulin E (IgE), and eosinophil count, were measured. Results Nineteen patients who benefited (responders) and 21 patients who failed (nonresponders) preoperative aspirin treatment with a distant history of ESS (mean, 48 months) were identified. Nonresponders were more likely to be African American (71%, p < 0.01) and have higher baseline IgE levels (252 kU/L vs 87 kU/L in responders, p < 0.01). 24 of the 40 patients (nine responders and 15 non‐responders) required subsequent ESS and underwent another aspirin desensitization 3‐4 weeks after ESS. All 24 patients tolerated a second round of aspirin desensitization and treatment. The primary aspirin therapy was associated with a significant increase in IgE in nonresponders, but there was no significant increase in IgE after the second aspirin desensitization and treatment. Conclusion Antecedent ESS enhances aspirin treatment responses in AERD patients and may convert patients who failed aspirin treatment before surgery to a more responsive phenotype after ESS. Patients with higher baseline serum IgE levels may benefit from ESS performed shortly before aspirin desensitization and therapy.