Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 ...Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: ∼25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5′ end of
TNRC9
, a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and ...rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 × 10−12 for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract only
e17023
Background: Combination of radiotherapy plus platinum-based chemotherapy (RT-CT) is considered the standard treatment in LACC. The risk of recurrence after local treatment is ...around 50-70%. The role of angiogenesis in tumor progression has been shown in large series. The aim of this study was to determinate the impact of the expression of VEGF and HIF-1 on disease-free survival (DFS) and overall survival (OS) in patients with LACC receiving RT-CT. Methods: Expression of VEGF and HIF–1 was assessed by an immunohistochemistry (IHC) assay in 115 cases. Inmunostainning was considered negative (< 10% of cells), slightly positive (< 25%), moderate (26%-50%) and strongly positive (> 50%). A univariate analysis was carried out for each variable using the log-rank test. Subsequently, a multivariate analysis was performed employing Cox’s proportional hazards model. Results: 115 patients (p) with LACC were included and received RT-CT between January/2003 and December/2012. IHC revealed absence of expression of VEGF in 12 (10,4%) cases, slightly positive in 34 (29,6%), moderate in 30 (26,1%) and strongly positive in 39 (33,9%). The expression of HIF-1 was negative in 63 (54,8%) cases and positive (weak or moderate) in 52 (45,2%). 76p (66,1%) showed a complete clinical response (CR), 26p (22,6%) partial response and 13p (11,3%) stable disease or progression. The median follow–up was 35 months (1-140). 56p (48,7%) relapsed. Univariate analysis indicate that ECOG > 1, tumor size ≥ 4,5 cm, FIGO stage III-IVA, lymph nodes positive, non CR, CA125 post-treatment ≥ 35 U/mL, hemoglobin levels <11 mg/dl (basal, nadir and post-treatment), strong expression VEGF and positive expression of HIF – 1 were all associated with a significant lower OS and DFS. In multivariate analysis strong expression of VEGF remained statistically significant, as tumor size, non CR and hemoglobin level post-treatment < 11g/dL. Conclusions: IHC-assessed strong expression of VEGF was independent prognostic factor of shorter OS and DFS in patients with LACC treated with RT-CT. IHC determination of VEGF could be useful in clinical practice.
Abstract only
e15603
Background: No globally accepted prognostic score has been developed in advanced gastric cancer (AGC). The purpose of this study is to explore baseline host or tumor related ...prognostic factors in spanish AGC patients in first and second line chemotherapy treatment. In addition we compare our scores with previously published scores in asian and european population. Methods: A total of 166 patients with AGC treated in our institution between 2012 and 2016 were screened. 119 received first line chemotherapy (CT) and 47 of them also received second line CT and were included in the analysis. Prognostic factors were evaluated using the Cox proportional hazard model. We use as comparators four first line and three second line scores published in literature. Results: The overal survival (OS) in first line and second line patients were 9 and 5 months. To construct first line CT score we selected four risk factors: ECOG≥2, Her2 negative, Irinotecan based CT and albumin < 3,6mg/dl. OS were 23 months in low risk group, who had zero or one risk points, 15 months for patients in the moderate risk group, who had two or three risk points, and 5 months for patients in the high risk group, who had all four risk points. In the second line CT score we included four risk factors: ECOG ≥2, albumin < 3.6mg/dl, Hb < 11.5mg/dl and CA19.9 reduction less than 30% after 2 CT cycles. OS were 30 months in low risk group, who had zero or one risk points, 16 months for patients in the moderate risk group, who had two or three risk points, and 3 months for patients in the high risk group, who had all four risk points. Conclusions: In the present study, we propose two new prognostic scores for patients with AGC developed in the same cohort and including HER2 status. This prognostic model could help clinicians choose and applicable treatment based on the stimated prognosis. Table: see text
Purpose: To explore the contribution of flow cytometry immunophenotyping (FCI) in detecting leptomeningeal disease in patients with solid tumors.
Experimental design: Cerebrospinal fluid (CSF) ...samples from 78 patients who received a diagnosis of epithelial-cell solid tumors and had clinical data suggestive of leptomeningeal carcinomatosis (LC) were studied. A novel FCI protocol was used to identify cells expressing the epithelial cell antigen EpCAM and their DNA content. Accompanying inflammatory cells were also described. FCI results (positive or negative for malignancy) were compared with those from CSF cytology and with the diagnosis established by the clinicians: patients with LC (n = 49), without LC (n = 26), and undetermined (n = 3).
Results: FCI described a wide range of EpCAM-positive cells with a hyperdiploid DNA content in the CSF of patients with LC. Compared with cytology, FCI showed higher sensitivity (75.5 vs 65.3) and negative predictive value (67.6 vs 60.5), and similar specificity (96.1 vs 100) and positive predictive value (97.4 vs 100). Concordance between cytology and FCI was high (Kp = 0.83), although misdiagnosis of LC did not show differences between evaluating the CSF with 1 or 2 techniques (P = .06). Receiver-operator characteristic curve analyses showed that lymphocytes and monocytes had a different distribution between patients with and without LC.
Conclusion: FCI seems to be a promising new tool for improving the diagnostic examination of patients with suspicion of LC. Detection of epithelial cells with a higher DNA content is highly specific of LC, but evaluation of the nonepithelial cell compartment of the CSF might also be useful for supporting this diagnosis.
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