15 research outputs found
Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
Abstract
Introduction
Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).
Methods
To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.
Results
Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).
Conclusions
The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers
Erratum to: nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial
nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial
<p><b>Article full text</b></p>
<p><br></p>
<p>The full text of this article can
be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-016-0327-4">https://link.springer.com/article/10.1007/s12325-016-0327-4</a></p><p></p>
<p><br></p>
<p><b>Provide enhanced content for this
article</b></p>
<p><br></p>
<p>If you are an author of this
publication and would like to provide additional enhanced content for your
article then please contact <a href="http://www.medengine.com/Redeem/ĂąÂÂmailto:[email protected]ĂąÂÂ"><b>[email protected]</b></a>.</p>
<p><br></p>
<p>The journal offers a range of
additional features designed to increase visibility and readership. All
features will be thoroughly peer reviewed to ensure the content is of the
highest scientific standard and all features are marked as âpeer reviewedâ to
ensure readers are aware that the content has been reviewed to the same level
as the articles they are being presented alongside. Moreover, all sponsorship
and disclosure information is included to provide complete transparency and
adherence to good publication practices. This ensures that however the content
is reached the reader has a full understanding of its origin. No fees are
charged for hosting additional open access content.</p>
<p><br></p>
<p>Other enhanced features include,
but are not limited to:</p>
<p><br></p>
<p>âą Slide decks</p>
<p>âą Videos and animations</p>
<p>âą Audio abstracts</p>
<p>âą Audio slides</p
Topoisomerase-II? expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel
Purpose: The predictive value of topoisomerase-II? (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel.Experimental design: Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m2 q3wks) with docetaxel (100 mg/m2 q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1).Results: Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03â1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94â1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content >10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87â6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04â0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content >10% (OR, 8.31; 95% confidence interval, 1.86â37.03; P = 0.05).Conclusions: (a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial
Physical Mapping of the Mouse Tilted Locus Identifies an Association between Human Deafness Loci DFNA6/14 and Vestibular System Development
Nutrition. Y a-t-il une place pour la supplĂ©mentation en acides gras omĂ©ga-3, en acides linolĂ©iques conjuguĂ©s et en micronutriments pendant et aprĂšs les traitements dâun cancer du sein ?
National audienc