37 research outputs found
Prognostic utility of HOXB13 : IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial
Background: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. Methods: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling. Results: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorized as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk. Conclusion: Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.Original Publication:Piiha-Lotta Jerevall, Xiai-Jun Ma, Hongying Li, Ranelle Salunga, Nicole C. Kesty, Mark G. Erlander, Dennis Sgroi, Birgitta Holmlund, Lambert Skoog, Tommy Fornander, Bo Nordenskjöld and Olle Stål, Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial, 2011, British Journal of Cancer, (104), 11, 1762-1769.http://dx.doi.org/10.1038/bjc.2011.145Copyright: Nature Publishing Grouphttp://npg.nature.com
Markers for the identification of late breast cancer recurrence
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited
Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer
Introduction\ud
Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).\ud
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Methods\ud
Tumor samples from 265 ER+LN- tamoxifen-treated patients were identified from a single academic institution's cancer research registry. The BCI assay was performed and scores were assigned based on a pre-determined risk model. Risk was assessed by BCI and AO and correlated to clinical outcomes in the patient cohort.\ud
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Results\ud
BCI was a significant predictor of outcome in a cohort of 265 ER+LN- patients (median age: 56-y; median follow-up: 10.3-y), treated with adjuvant tamoxifen alone or tamoxifen with chemotherapy (32%). BCI categorized 55%, 21%, and 24% of patients as low, intermediate and high-risk, respectively. The 10-year rates of distant recurrence were 6.6%, 12.1% and 31.9% and of breast cancer-specific mortality were 3.8%, 3.6% and 22.1% in low, intermediate, and high-risk groups, respectively. In a multivariate analysis including clinicopathological factors, BCI was a significant predictor of distant recurrence (HR for 5-unit increase = 5.32 [CI 2.18-13.01; P = 0.0002]) and breast cancer-specific mortality (HR for a 5-unit increase = 9.60 [CI 3.20-28.80; P < 0.0001]). AO was significantly associated with risk of recurrence. In a separate multivariate analysis, both BCI and AO were significantly predictive of outcome. In a time-dependent (10-y) ROC curve accuracy analysis of recurrence risk, the addition of BCI+AO increased predictive accuracy in all patients from 66% (AO only) to 76% (AO+BCI) and in tamoxifen-only treated patients from 65% to 81%.\ud
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Conclusions\ud
This study validates the prognostic performance of BCI in ER+LN- patients. In this characteristically low-risk cohort, BCI classified high versus low-risk groups with ~5-fold difference in 10-year risk of distant recurrence and breast cancer-specific death. BCI and AO are independent predictors with BCI having additive utility beyond standard of care parameters that are encompassed in AO
The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex
<p>Abstract</p> <p>Background</p> <p>The relationships between total serum IgE levels and gene expression patterns in peripheral blood CD4+ T cells (in all subjects and within each sex specifically) are not known.</p> <p>Methods</p> <p>Peripheral blood CD4+ T cells from 223 participants from the Childhood Asthma Management Program (CAMP) with simultaneous measurement of IgE. Total RNA was isolated, and expression profiles were generated with Illumina HumanRef8 v2 BeadChip arrays. Modeling of the relationship between genome-wide gene transcript levels and IgE levels was performed in all subjects, and stratified by sex.</p> <p>Results</p> <p>Among all subjects, significant evidence for association between gene transcript abundance and IgE was identified for a single gene, the interleukin 17 receptor B (IL17RB), explaining 12% of the variance (r<sup>2</sup>) in IgE measurement (p value = 7 × 10<sup>-7</sup>, 9 × 10<sup>-3 </sup>after adjustment for multiple testing). Sex stratified analyses revealed that the correlation between IL17RB and IgE was restricted to males only (r<sup>2 </sup>= 0.19, p value = 8 × 10<sup>-8</sup>; test for sex-interaction p < 0.05). Significant correlation between gene transcript abundance and IgE level was not found in females. Additionally we demonstrated substantial sex-specific differences in IgE when considering multi-gene models, and in canonical pathway analyses of IgE level.</p> <p>Conclusions</p> <p>Our results indicate that IL17RB may be the only gene expressed in CD4+ T cells whose transcript measurement is correlated with the variation in IgE level in asthmatics. These results provide further evidence sex may play a role in the genomic regulation of IgE.</p
Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer
Case–control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk
Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg213His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case–control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens