EREG

Gene Summary

Gene:EREG; epiregulin
Aliases: ER, Ep, EPR
Location:4q13.3
Summary:This gene encodes a secreted peptide hormone and member of the epidermal growth factor (EGF) family of proteins. The encoded protein is a ligand of the epidermal growth factor receptor (EGFR) and the structurally related erb-b2 receptor tyrosine kinase 4 (ERBB4). The encoded protein may be involved in a wide range of biological processes including inflammation, wound healing, oocyte maturation, and cell proliferation. Additionally, the encoded protein may promote the progression of cancers of various human tissues. [provided by RefSeq, Jul 2015]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:proepiregulin
Source:NCBIAccessed: 16 March, 2017

Ontology:

What does this gene/protein do?
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Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 16 March 2017 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 16 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (6)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: EREG (cancer-related)

Chang JS, Hsiao JR, Chen CH
ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective.
J Biomed Sci. 2017; 24(1):19 [PubMed] Free Access to Full Article Related Publications
The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

Chou ST, Hsiang CY, Lo HY, et al.
Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice.
BMC Complement Altern Med. 2017; 17(1):121 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Zuo-Jin-Wan (ZJW), a two-herb formula consisting of Coptis chinensis (CC) and Evodia rutaecarpa (ER), is commonly used in traditional Chinese medicine for the treatment of cancers. However, the efficacies and mechanisms of ZJW and its alkaloid components on cancers are still unclear.
METHODS: Here we investigated the anti-cancer effects and mechanisms of ZJW, CC, ER, berberine, and evodiamine in cells and in intrahepatic xenograft mice.
RESULTS: Treatment of HepG2 cells with ZJW, CC, ER, berberine, and evodiamine significantly displayed cytotoxic effects in a dose- and time-dependent manner. Hierarchical cluster analysis of gene expression profiles showed that CC and ZJW shared a similar mechanism for the cytotoxic effects, suggesting that CC was the active ingredient of ZJW for anti-cancer activity. Network analysis further showed that c-myc was the likely key molecule involved in the regulation of ZJW-affected gene expression. A human hepatoma xenograft model was established by intrahepatic injection of HepG2 cells containing nuclear factor-κB-driven luciferase genes in immunocompetent mice. In vivo bioluminescence imaging showed that cells had been successfully transplanted in mouse liver. Oral administration of ZJW for 28 consecutive days led to a significant decrease in the accumulation of ascites, the ratio of tumor-to-liver, and the number of transplanted cells in livers.
CONCLUSIONS: In conclusion, our findings suggested for the first time that ZJW significantly suppressed human cancer cell growth in orthotopic HepG2 xenograft-bearing immunocompetent mice. Moreover, c-myc might play a potent role in the cytotoxic mechanisms of ZJW, CC, ER, berberine, and evodiamine.

Cheng S, Castillo V, Welty M, et al.
BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo.
BMC Complement Altern Med. 2017; 17(1):115 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer.
METHODS: Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry.
RESULTS: Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer.
CONCLUSION: BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.

Pan JQ, Zhang YQ, Wang JH, et al.
lncRNA co-expression network model for the prognostic analysis of acute myeloid leukemia.
Int J Mol Med. 2017; 39(3):663-671 [PubMed] Related Publications
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with great variability of prognostic behaviors. Previous studies have reported that long non-coding RNAs (lncRNAs) play an important role in AML and may thus be used as potential prognostic biomarkers. However, thus use of lncRNAs as prognostic biomarkers in AML and their detailed mechanisms of action in this disease have not yet been well characterized. For this purpose, in the present study, the expression levels of lncRNAs and mRNAs were calculated using the RNA-seq V2 data for AML, following which a lncRNA‑lncRNA co-expression network (LLCN) was constructed. This revealed a total of 8 AML prognosis‑related lncRNA modules were identified, which displayed a significant correlation with patient survival (p≤0.05). Subsequently, a prognosis-related lncRNA module pathway network was constructed to interpret the functional mechanism of the prognostic modules in AML. The results indicated that these prognostic modules were involved in the AML pathway, chemokine signaling pathway and WNT signaling pathway, all of which play important roles in AML. Furthermore, the investigation of lncRNAs in these prognostic modules suggested that an lncRNA (ZNF571-AS1) may be involved in AML via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway by regulating KIT and STAT5. The results of the present study not only provide potential lncRNA modules as prognostic biomarkers, but also provide further insight into the molecular mechanisms of action of lncRNAs.

Jeong YJ, Jung JW, Cho YY, et al.
Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT.
Nucl Med Rev Cent East Eur. 2017; 20(1):32-38 [PubMed] Related Publications
BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.
MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.
RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).
CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.

Juergens RA, Bratman SV, Tsao MS, et al.
Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck.
Cancer Treat Rev. 2017; 54:43-57 [PubMed] Related Publications
The identification of common molecular aberrations that drive cancer progression has led to targeted therapies that improve treatment efficacy in many tumor types. Epidermal growth factor receptor (EGFR) inhibitors have been used to treat both lung and head and neck cancers with squamous cell histology. These tumors often show high EGFR expression and/or increased gene copy number, but low incidence of the activating kinase domain mutations common to adenocarcinomas of the lung. In this manuscript, we review clinical trial data on EGFR-inhibitors in the treatment of squamous cell carcinoma (SqCC) of the lung and head and neck (SCCHN), including both efficacy and biomarker analyses. Although some efficacy with use of EGFR inhibitors is observed, the level of benefit varies within and across tumor types, and the predictive capacity of high EGFR protein expression and/or gene amplification, if any, is limited. Due to the lack of candidate biomarkers that consistently predict response to EGFR-inhibitor therapy across treatment setting and class of agent in SqCC of the lung and SCCHN, we explore the biology, genomics and patterns of response to EGFR-inhibitors to inform identification of potential biomarkers, highlighting several key molecules that have shown promise in preclinical studies and clinical trials across multiple cancer sites.

Xia S, Ji R, Zhan W
Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/β-catenin signaling pathway.
BMC Neurol. 2017; 17(1):30 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. However, the biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown.
METHODS: The expression level of lncRNA PTCSC3 in human microglia and glioma cell lines was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The influence of lncRNA PTCSC3 on cell proliferation were studied using the cell counting kit-8, and cell cycle and apoptosis were analyzed by flow cytometry assays. The migration and invasion abilities were investigated by transwell and wound healing assays. The target genes of lncRNA PTCSC3 were explored by qRT-PCR, immunofluorescence and western blot.
RESULTS: LncRNA PTCSC3 was significantly downregulated in glioma cell lines. The overexpression of lncRNA PTCSC3 suppressed proliferation and induced apoptosis in U87 and U251 cells. Additionally, the overexpression of lncRNA PTCSC3 inhibited the migration and invasion of U87 and U251 cells. Moreover, lncRNA PTCSC3 inhibited the epithelial-mesenchymal transition of U87 cells. The study also demonstrated that LRP6, as a receptor of the Wnt/β-catenin pathway, was a target of lncRNA PTCSC3. By evaluating the expression levels of Axin1, active β-catenin, c-myc, and cyclin D1, the study indicated that lncRNA PTCSC3 inhibited the activation of the Wnt/β-cateninpathway through targeting LRP6.
CONCLUSIONS: LncRNA PTCSC3 inhibits the proliferation and migration of glioma cells and suppresses Wnt/β-catenin signaling pathway by targeting LRP6. LncRNA PTCSC3 is a potential therapeutic target for treatment of glioma.

Wu HC, Southey MC, Hibshoosh H, et al.
DNA Methylation in Breast Tumor from High-risk Women in the Breast Cancer Family Registry.
Anticancer Res. 2017; 37(2):659-664 [PubMed] Related Publications
To examine DNA methylation profiles in breast tumors of women with a strong breast cancer family history, we measured methylation by bisulfite sequencing in 40 genes in 40 breast tumor tissues from women in the Breast Cancer Family Registry. We selected candidate genes from analysis of the Cancer Genome Atlas project (TCGA) breast data. Compared to TCGA breast cancer, BCFR cases are younger and more likely to be ER-negative. Overall, we found that many of the methylation differences between BCFR tumor and normal adjacent tissues were smaller than that in TCGA samples. We found only 32% of tested genes were hypermethylated in BCFR; the largest difference was 36.1% for SEPW1, and the smallest difference was 10% for RYR2. These data suggest the importance of examining breast cancer cases including familial cases enriched with early-onset cancers to identify methylation markers that can be examined in blood as biomarkers for early detection.

Agosto-Arroyo E, Isayeva T, Wei S, et al.
Differential Gene Expression in Ductal Carcinoma In Situ of the Breast Based on ERBB2 Status.
Cancer Control. 2017; 24(1):102-110 [PubMed] Related Publications
BACKGROUND: The molecular signature of ductal carcinoma in situ (DCIS) in the breast is not well understood. Erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly known as HER2/neu]) positivity in DCIS is predictive of coexistent early invasive breast carcinoma. The aim of this study is to identify the gene-expression signature profiles of estrogen receptor (ER)/progesterone receptor (PR)-positive, ERBB2, and triple-negative subtypes of DCIS.
METHODS: Based on ER, PR, and ERBB2 status, a total of 18 high nuclear grade DCIS cases with no evidence of invasive breast carcinoma were selected along with 6 non-neoplastic controls. The 3 study groups were defined as ER/PR-positive, ERBB2, and triple-negative subtypes.
RESULTS: A total of 49 genes were differentially expressed in the ERBB2 subtype compared with the ER/PR-positive and triple-negative groups. PROM1 was overexpressed in the ERBB2 subtype compared with ER/PR-positive and triple-negative subtypes. Other genes differentially expressed included TAOK1, AREG, AGR3, PEG10, and MMP9.
CONCLUSIONS: Our study identified unique gene signatures in ERBB2-positive DCIS, which may be associated with the development of invasive breast carcinoma. The results may enhance our understanding of the progression of breast cancer and become the basis for developing new predictive biomarkers and therapeutic targets for DCIS.

Zhang M, Zhuang G, Sun X, et al.
TP53 mutation-mediated genomic instability induces the evolution of chemoresistance and recurrence in epithelial ovarian cancer.
Diagn Pathol. 2017; 12(1):16 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. We attempted to gain insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1.
METHODS: TP53 mutation status was assessed by performing nucleotide sequencing and immunohistochemistry. Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. DNA copy number was analyzed by performing fluorescence in situ hybridization (FISH).
RESULTS: In addition to performing nucleotide sequencing for 5 cases of ovarian cancer, TP53 mutations were analyzed via immunohistochemical staining for P53. Both intensive P53 immunohistochemical staining and complete absence of signal were associated with the occurrence of TP53 mutations. HE staining and the quantification of DNA content indicated a significantly higher proportion of polyploidy and aneuploidy cells in the TP53 mutant group than in the wild-type group (p < 0.05). Moreover, in 161 epithelial ovarian cancer patients, multivariate logistic analysis identified late FIGO (International Federation of Gynecology and Obstetrics) stage, serous histotype, G3 grade and TP53 mutation as independent risk factors for ovarian cancer recurrence. In relapse patients, the proportion of chemoresistant cases in the TP53 wild-type group was significantly lower than in the mutant group (63.6% vs. 91.8%, p < 0.05). FISH results revealed a higher percentage of cells with >6 MDR1 copies and chromosome 7 amplication in the TP53 mutant group than in the wild-type group [11.7 ± 2.3% vs. 3.0 ± 0.7% and 2.1 ± 0.7% vs. 0.3 ± 0.05%, (p < 0.05), respectively]. And we observed a specific increase of MDR1 and chromosome 7 copy numbers in the TP53 mutant group upon disease regression (p < 0.01).
CONCLUSIONS: TP53 mutation-associated genomic instability may promote chromosome 7 accumulation and MDR1 amplification during ovarian cancer chemoresistance and recurrence. Our findings lay the foundation for the development of promising chemotherapeutic approaches to treat aggressive and recurrent ovarian cancer.

Gu HF, Mou M, Liang ZG, et al.
The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome.
Cell Mol Biol (Noisy-le-grand). 2016; 62(14):44-47 [PubMed] Related Publications
Some studies investigated the association of paraoxonase 1 (PON1) polymorphisms with polycystic ovarian syndrome (PCOS) risk. However, the result was still inconsistent. The aim of this study was to investigate whether there is an association between the PON1 polymorphisms and PCOS risk. Electronic databases, such as PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched for identification of the studies. The associations between PON1 polymorphisms and PCOS risk was quantified using ORs with 95% CIs. A total of 8 eligible studies with 2272 cases and 1811 controls were included in this meta-analysis. PON1 Leu55Met polymorphism was associated with a significantly increased risk of PCOS (OR=1.31; 95%CI, 1.10-1.55). However, no association was found in Asians and Caucasians (Table 2). We also found that PON1 Q192R polymorphism was associated with a significantly increased risk of PCOS (OR=1.81; 95%CI, 1.17-2.82). Additionally, this polymorphism increased PCOS risk in Asians (OR=1.26; 95%CI, 1.13-1.41). Furthermore, PON1 C108T polymorphism showed increased PCOS risk (OR=1.46; 95%CI, 1.08-1.97). No association between this polymorphism and PCOS risk was found in Asians and Caucasians. In conclusion, this meta-analysis suggested that PON1 polymorphisms were associated with PCOS risk.

Buttigliero C, Tucci M, Vignani F, et al.
Molecular biomarkers to predict response to neoadjuvant chemotherapy for bladder cancer.
Cancer Treat Rev. 2017; 54:1-9 [PubMed] Related Publications
Cystectomy is the gold standard for treatment of localized muscle-invasive bladder cancer. However, about 50% of patients develop metastases within 2years after cystectomy and subsequently die for the disease. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival in patients with muscle-invasive bladder cancer, and pathological response to neoadjuvant treatment (downstaging to ⩽pT1 at cystectomy) is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from neoadjuvant therapy. The identification of reliable biomarkers that could enable the clinicians to identify patients who will really benefit from neoadjuvant chemotherapy is a major issue. This approach could lead to individualized therapy, in order to optimize the chance of response, avoiding the impact of neoadjuvant treatment on quality of life and the delay of cystectomy in non-responder patients. However, no molecular predictive biomarkers have shown clinical utility. This paper aims to review currently available data about biomarkers predictive of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

López JI, Erramuzpe A, Guarch R, et al.
CD34 immunostaining enhances a distinct pattern of intratumor angiogenesis with prognostic implications in clear cell renal cell carcinoma.
APMIS. 2017; 125(2):128-133 [PubMed] Related Publications
Clear cell renal cell carcinoma is an aggressive neoplasm related to VHL gene inactivation. The molecular events derived from this initial alteration lead to a permanent intracellular pseudo-hypoxic status that stimulates vascular proliferation. The resulting increased intratumor angiogenesis is the target of most modern therapies. Although intratumor angiogenesis has received full attention in the last years, few studies have focused on its potential importance from a strict morphological approach. Intratumor angiogenesis has been analyzed in a retrospective series of clear cell renal cell carcinomas (n = 208) with long-term follow-up (n = 177). Two different patterns of angiogenesis have been highlighted with CD34 at the front of tumor invasion, termed continuous and discontinuous, respectively. The continuous pattern of angiogenesis showed a complete microvascular network surrounding totally tumor nests. Conversely, the discontinuous pattern displayed an incomplete network around tumor nests. The continuous pattern was associated to shorter 5-year (p = 0.00064, hazard ratio = 2.8) and 15-year (p = 0.014, hazard ratio = 1.7) survivals. Cox regression multivariate analysis also showed that the continuous pattern (p = 0.016373) remains a significant variable when considered together with grade (p = 0.001755) and stage (p = 0.000952). These findings support the notion that a continuous CD34(+) pattern of intratumor angiogenesis may be useful for pathologists in predicting tumor behavior in clear cell renal cell carcinomas.

Rezende LM, Marson FA, Lima CS, Bertuzzo CS
Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer.
Gene. 2017; 608:73-78 [PubMed] Related Publications
INTRODUCTION: Reproductive factors pose a risk for sporadic breast cancer (BC) development owing to the lifetime exposure to estrogen, a hormone responsible for cell proliferation in the breast. Because variants of the estrogen receptor (ER) alpha and beta genes have been associated with BC risk in numerous populations, the objective of the study was to determine whether the risk and severity of sporadic BC was associated with the rs2228480 (ESR1) and rs4986938 (ESR2) variants in a Brazilian population.
METHODS: A total of 253 DNA samples from sporadic BC patients and 257 DNA samples from healthy controls were studied. The samples were genotyped by PCR-RFLP. Epidemiological, clinical, and reproductive factors were analyzed. Statistical tests conducted included the χ(2) test, Fisher's exact test, and Mann-Whitney and Kruskal-Wallis tests or their parametric equivalents.
RESULTS: There was a high frequency of the rs2228480*GG genotype among the ER-positive tumors (OR=2.13; 95% CI=1.189-3.816) and it showed minor association with clinical stage 0 (OR=0.324; 95% CI=0.116-0.904). The rs2228480*GA genotype was associated with minor ER expression, whereas rs2228480*GG was associated with high expression of the progesterone receptor (PR). The frequency of rs4986938*GA was high among women who breastfed (OR=2.11; 95% CI=1.203-3.702), and it showed high association with clinical stage 0 (OR=4.383; 95% CI=1.606-11.96) whereas it had minor association with systemic arterial hypertension (OR=0.53; 95% CI=0.319-0.880). The rs2228480*GG/rs4986938*GG haplotype occurred at a low frequency among women who breastfed (OR=0.525; 95% CI=0.298-0.924) but it was associated with a high expression of PR.
CONCLUSION: The rs2228480 and rs4986938 variants did not alter sporadic BC risk, but they did modulate the BC severity.

Zhang CZ
Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression.
Gene. 2017; 607:47-55 [PubMed] Related Publications
A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) during tumorigenesis. In this study, the qRT-PCR results revealed that the lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) was over-expressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. Ectopic expression of FTH1P3 facilitates cell proliferation and colony formation in OSCC cells. Moreover, FTH1P3 acted as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-224-5p and thereby modulating the expression of fizzled 5. Importantly, expression analysis revealed that both FTH1P3 and fizzled 5 were up-regulated in OSCC cell lines and tissues, and over-expression of fizzled 5 also functioned as an oncogene in OSCC cells. Our data demonstrated FTH1P3 facilitated OSCC progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Thus, targeting the ceRNA network referring FTH1P3 may be a therapeutic target for treatment of OSCC.

Murphy SE
Nicotine Metabolism and Smoking: Ethnic Differences in the Role of P450 2A6.
Chem Res Toxicol. 2017; 30(1):410-419 [PubMed] Related Publications
Nicotine is the primary addictive agent in tobacco, and P450 2A6 (gene name: CYP2A6) is the primary catalyst of nicotine metabolism. It was proposed more than 20 years ago that individuals who metabolize nicotine poorly would smoke less, either fewer cigarettes per day or less intensely per cigarette, compared to smokers who metabolize nicotine more efficiently. These poor metabolizers would then be less likely to develop lung cancer due to their lower exposure to the many carcinogens delivered with nicotine in each puff of smoke. Numerous studies have reported that smokers who carry reduced activity or null CYP2A6 alleles do smoke less. Yet only in Asian populations, both Japanese and Chinese, which have a high prevalence of genetic variants, has a link between CYP2A6, smoking dose, and lung cancer been established. In other ethnic groups, it has been challenging to confirm a direct link between P450 2A6-mediated nicotine metabolism and the risk of lung cancer. This challenge is due in part to the difficulty in accurately quantifying smoking dose and accurately predicting or measuring P450 2A6-mediated nicotine metabolism. Biomarkers of nicotine metabolism and smoking exposure, including the ratio of trans-3-hydroxycotine to cotinine, a measure of P450 2A6 activity and plasma cotinine, or urinary total nicotine equivalents (the sum of nicotine and six metabolites) as measures of exposure are useful for addressing this challenge. However, to take full advantage of these biomarkers in the study of ethnic/racial differences in the risk of lung cancer requires the complete characterization of nicotine metabolism across ethnic/racial groups. Variation in metabolism pathways, other than those catalyzed by P450 2A6, can impact biomarkers of both nicotine metabolism and dose. This is clearly important for smokers with low levels of UGT2B10-catalyzed nicotine and cotinine glucuronidation because the UGT2B10 genotype influences plasma cotinine levels. Cotinine is not glucuronidated in 15% of African American smokers (compared to 1% of Whites) due to the prevalence of a UGT2B10 splice variant. This variant contributes significantly to the higher plasma cotinine levels per cigarette in this group and may also influence the accuracy of the 3HCOT to cotinine ratio as a measure of P450 2A6 activity.

Chen JR, Chien HP, Chen KS, et al.
Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer.
Medicine (Baltimore). 2017; 96(2):e5582 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan.
METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization.
RESULTS: TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts.
CONCLUSION: Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.

Gao XH, Li J, Liu Y, et al.
ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer.
Medicine (Baltimore). 2017; 96(1):e5845 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Competing endogenous RNA (ceRNA) regulation is a novel hypothesized mechanism that states RNA molecules share common target microRNAs (miRNAs) and may competitively combine into the same miRNA pool.
METHODS: Zinc finger protein 148 (ZNF148) and TOP2A expression were analyzed in 742 colorectal cancer (CRC) tissues using immunohistochemistry (IHC). ZNF148 mRNA, TOP2A mRNA, miR101, miR144, miR335, and miR365 expression were estimated in 53 fresh frozen CRC tissues by reverse transcription polymerase chain reaction. Mechanisms underpinning ceRNA were examined using bioinformatics, correlation analysis, RNA interference, gene over-expression, and luciferase assays.
RESULTS: Protein levels of ZNF148 and TOP2A detected by IHC positively correlated (Spearman correlation coefficient [rs] = 0.431, P < 0.001); mRNA levels of ZNF148 and TOP2A also positively correlated (r = 0.591, P < 0.001). Bioinformatics analysis demonstrated that ZNF148 and TOP2A mRNA had 13 common target miRNAs, including miR101, miR144, miR335, and miR365. Correlation analysis demonstrated that levels of ZNF148 mRNA were negatively associated with levels of miR144, miR335, and miR365. Knockdown and overexpression tests showed that ZNF148 mRNA and TOP2A mRNA regulated each other in HCT116 cells, respectively, but not in Dicer-deficient HCT116 cells. Luciferase assays demonstrated that ZNF148 and TOP2A regulated each other through 3'UTR. Overexpression of ZNF148 mRNA and TOP2A mRNA caused significant downregulation of miR101, miR144, miR335, and miR365 in the HCT116 cells. We also found that knockdown of ZNF148 and TOP2A significantly promoted cell growth, and overexpression of ZNF148 and TOP2A inhibited cell proliferation, which was abrogated in Dicer-deficient HCT116 cells.
CONCLUSION: ZNF148 and TOP2A regulate each other through ceRNA regulatory mechanism in CRC, which has biological effects on cell proliferation.

Gai L, Liu H, Cui JH, et al.
The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.
Gene. 2017; 605:123-130 [PubMed] Related Publications
The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis.

Zhou Z, Luo A, Shrivastava I, et al.
Regulation of XIAP Turnover Reveals a Role for USP11 in Promotion of Tumorigenesis.
EBioMedicine. 2017; 15:48-61 [PubMed] Free Access to Full Article Related Publications
The emerging regulatory role of deubiquitinases (DUBs) has been implicated in various fundamental processes and pathogenesis. To determine the pivotal role that DUBs play in mediating tumorigenesis, we have performed a non-biased screen of 67 human DUBs based on a mammary cell transformation assay. This led to the identification of USP11 as a critical determinant of mammary tumor initiation and progression. Using an approach of protein complex purification coupled with mass spectrometry, we further identified XIAP to be a target for USP11. We demonstrated that, while depletion of XIAP attenuates cell transformation, elevated USP11 significantly promotes the tumor colony formation through stabilization of XIAP. Molecular modeling coupled with mutagenesis analyses further revealed that Leu207 on the BIR2 domain of XIAP facilitates its interaction with USP11. Stabilization of XIAP due to its deubiquitylation by USP11 leads to the inhibition of cell anoikis and apoptosis, which in turn promotes tumorigenesis. Finally, immunohistochemical staining revealed that aberrant accumulation of USP11 correlates with elevated levels of XIAP in breast cancer tissues. We therefore propose that aberrant USP11, via stabilization of XIAP, promotes tumor initiation and progression.

Kurian AW, Friese CR, Bondarenko I, et al.
Second Opinions From Medical Oncologists for Early-Stage Breast Cancer: Prevalence, Correlates, and Consequences.
JAMA Oncol. 2017; 3(3):391-397 [PubMed] Related Publications
Importance: Advances in the evaluation and treatment of breast cancer have made the clinical decision-making context much more complex. A second opinion from a medical oncologist may facilitate decision making for women with breast cancer, yet little is known about second opinion use.
Objective: To investigate the patterns and correlates of second opinion use and the effect on chemotherapy decisions.
Design, Setting, and Participants: A total of 1901 women newly diagnosed with stages 0 to II breast cancer between July 2013 and September 2014 (response rate, 71.0%) were accrued through 2 population-based Surveillance, Epidemiology, and End Results registries (Georgia and Los Angeles County, California) and surveyed about their experiences with medical oncologists, decision making, and chemotherapy use.
Main Outcomes and Measures: Factors associated with second opinion use were evaluated using logistic regression. Also assessed was the association between second opinion and chemotherapy use, adjusting for chemotherapy indication and propensity for receiving a second opinion. Multiple imputation and weighting were used to account for missing data.
Results: A total of 1901 patients with stage I to II breast cancer (mean [SD] age, 61.6 [11.0] years; 1071 [56.3%] non-Hispanic white) saw any medical oncologist. Analysis of multiply imputed, weighted data (mean n = 1866) showed that 168 (9.8%) (SE, 0.74%) received a second opinion and 54 (3.2%) (SE, 0.47%) received chemotherapy from the second oncologist. Satisfaction with chemotherapy decisions was high and did not differ between those who did (mean [SD], 4.3 [0.08] on a 1- to 5-point scale) or did not (4.4 [0.03]) obtain a second opinion (P = .29). Predictors of second opinion use included college education vs less education (odds ratio [OR], 1.85; 95% CI, 1.24-2.75), frequent use of internet-based support groups (OR, 2.15; 95% CI, 1.12-4.11), an intermediate result on the 21-gene recurrence score assay (OR, 1.85; 95% CI, 1.11-3.09), and a variant of uncertain significance on hereditary cancer genetic testing (OR, 3.24; 95% CI, 1.09-9.59). After controlling for patient and tumor characteristics, second opinion use was not associated with chemotherapy receipt (OR, 1.04; 95% CI, 0.71-1.52).
Conclusions and Relevance: Second opinion use was low (<10%) among patients with early-stage breast cancer, and high decision satisfaction regardless of second opinion use suggests little unmet demand. Along with educational level and use of internet support groups, uncertain results on genomic testing predicted second opinion use. Patient demand for second opinions may increase as more complex genomic tests are disseminated.

Imai T, Oue N, Sentani K, et al.
KIF11 Is Required for Spheroid Formation by Oesophageal and Colorectal Cancer Cells.
Anticancer Res. 2017; 37(1):47-55 [PubMed] Related Publications
BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC) are common types of human cancer. Spheroid colony formation is used to characterize cancer stem cell (CSCs). In the present study, we analyzed the significance of kinesin family 11 (KIF11 in human ESCC and CRC.
MATERIALS AND METHODS: Expression of KIF11 in 105 ESCC and 100 CRC cases was determined using immunohistochemistry. RNA interference was used to inhibit KIF11 expression in ESCC and CRC cell lines.
RESULTS: In total, 61 out of 105 (58%) ESCC and 62 out of 100 (62%) CRC cases were positive for KIF11. Expression of KIF11 was not associated with any clinicopathological characteristics. Both the number and size of spheres produced by from TE-5 ESCC cells and DLD-1 CRC cells were significantly reduced upon KIF11 siRNA transfection compared to negative control siRNA transfection.
CONCLUSION: These results indicate that KIF11 plays an important role in CSCs of ESCC and CRC.

Rodriguez-Salas N, Dominguez G, Barderas R, et al.
Clinical relevance of colorectal cancer molecular subtypes.
Crit Rev Oncol Hematol. 2017; 109:9-19 [PubMed] Related Publications
Colorectal cancer (CRC) is characterized by alteration of critical pathways such TP53 inactivation, BRAF, PI3CA mutations, APC inactivation, KRAS, TGF-β, CTNNB mutations, disregulation of Epithelial to mesnechymal transition (EMT) genes, WNT signaling activation, MYC amplification, and others. Differences in these molecular events results in differences in phenotypic characteristics of CRC, that have been studied and classified by different models of molecular subtypes. It could have potential applications to prognosis, but also to therapeutical approaches of the CRC patients. We review and summarized the different molecular classifications and try to clarify their clinical and therapeutical relevance.

Zhang M, Sui C, Dai B, et al.
PEG10 is imperative for TGF-β1-induced epithelial‑mesenchymal transition in hepatocellular carcinoma.
Oncol Rep. 2017; 37(1):510-518 [PubMed] Related Publications
Substantial evidence indicates that transforming growth factor-beta 1 (TGF-β1) plays a vital role in epithelial-mesenchymal transition (EMT). PEG10 has been shown involved in invasion and metastasis of tumors. The present study investigated the role of PEG10 in TGF-β1-triggered EMT in hepatocellular carcinoma (HCC) progression. Immunohistochemistry and real-time PCR were used to measure the expression level of PEG10 in clinical HCC tissues with or without lymph node metastasis, and normal tissues. The results showed that PEG10 expression is higher in HCC tissues and associated with overall survival (OS) and lymph node metastasis. Moreover, PEG10 expression level was remarkably higher in hepatic cancer cells than the normal hepatic cell line L02. In the present study, we constructed an adenovirus vector containing the coding area of PEG10 (Ad-PEG10) and infected HepG2 cells and found that overexpression of PEG10 promoted the cell migration, invasion ability and EMT of HepG2 cells. TGF-β1 acted on HepG2 cells by enhancing cell migration, invasion, EMT and upregulating PEG10 expression level. However, cells pretreated with adenovirus vector of PEG10 shRNAs (Ad-shRNA1 and Ad-shRNA2) did not occur EMT prior to TGF-β1 stimulation. Moreover, TGF-β1 did not increase the migration and invasion of cells with PEG10 knockdown and overexpression of PEG10 confers chemoresistance to HepG2 cells. Accordingly, sufficient PEG10 expression level is essential for TGF-β1 induced EMT and associated with the chemoresistance in HepG2 cells.

Xu G, Zhang M, Zhu H, Xu J
A 15-gene signature for prediction of colon cancer recurrence and prognosis based on SVM.
Gene. 2017; 604:33-40 [PubMed] Related Publications
OBJECTIVE: To screen the gene signature for distinguishing patients with high risks from those with low-risks for colon cancer recurrence and predicting their prognosis.
METHODS: Five microarray datasets of colon cancer samples were collected from Gene Expression Omnibus database and one was obtained from The Cancer Genome Atlas (TCGA). After preprocessing, data in GSE17537 were analyzed using the Linear Models for Microarray data (LIMMA) method to identify the differentially expressed genes (DEGs). The DEGs further underwent PPI network-based neighborhood scoring and support vector machine (SVM) analyses to screen the feature genes associated with recurrence and prognosis, which were then validated by four datasets GSE38832, GSE17538, GSE28814 and TCGA using SVM and Cox regression analyses.
RESULTS: A total of 1207 genes were identified as DEGs between recurrence and no-recurrence samples, including 726 downregulated and 481 upregulated genes. Using SVM analysis and five gene expression profile data confirmation, a 15-gene signature (HES5, ZNF417, GLRA2, OR8D2, HOXA7, FABP6, MUSK, HTR6, GRIP2, KLRK1, VEGFA, AKAP12, RHEB, NCRNA00152 and PMEPA1) were identified as a predictor of recurrence risk and prognosis for colon cancer patients.
CONCLUSION: Our identified 15-gene signature may be useful to classify colon cancer patients with different prognosis and some genes in this signature may represent new therapeutic targets.

Huang CF, Huang CY, Yeh ML, et al.
Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment.
EBioMedicine. 2017; 15:81-89 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIMS: The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCC) related hepatocellular carcinoma. The impact of the genetic variants and its serum levels on post-treatment cohort is elusive.
METHODS: MICA rs2596542 genotype and serum MICA (sMICA) levels were evaluated in 705 patients receiving antiviral therapy.
RESULTS: Fifty-eight (8·2%) patients developed HCC, with a median follow-up period of 48·2months (range: 6-129months). The MICA A allele was associated with a significantly increased risk of HCC development in cirrhotic non-SVR patients but not in patients of non-cirrhotic and/or with SVR. For cirrhotic non-SVR patients, high sMICA levels (HR/CI: 5·93/1·86-26.38·61, P=0·002) and the MICA rs2596542 A allele (HR/CI: 4·37/1·52-12·07, P=0·002) were independently associated with HCC development. The risk A allele or GG genotype with sMICA>175ng/mL provided the best accuracy (79%) and a negative predictive value of 100% in predicting HCC.
CONCLUSIONS: Cirrhotic patients who carry MICA risk alleles and those without risk alleles but with high sMICA levels possessed the highest risk of HCC development once they failed antiviral therapy.

Qiu ZL, Shen CT, Sun ZK, et al.
Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting 131I Uptake and Mortality in Papillary Thyroid Cancer Patients with Lung Metastases.
Cell Physiol Biochem. 2016; 40(6):1377-1390 [PubMed] Related Publications
PURPOSE: The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases.
METHODS: The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis.
RESULTS: Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(P<0.001).
CONCLUSIONS: ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC.

Zheng J, Wang L, Peng Z, et al.
Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma.
EBioMedicine. 2017; 15:62-72 [PubMed] Free Access to Full Article Related Publications
Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In this study, samples from primary ccRCC tumor and their corresponding nontumor adjacent tissues (n=18) were analyzed by quantitative proteomic assay. Proteins downregulated in tumors were studied by GO and KEGG pathways enrichment analyses. Six proteins were found both downregulated and annotated with cell proliferation in ccRCC patients. Of these proteins, PDZK1 and FABP1 were also involved in the lipid metabolism pathway. The downregulation of PDZK1 was further validated in TCGA_KIRC dataset (n=532) and independent set (n=202). PDZK1 could discriminate recurrence, metastasis and prognosis between ccRCC patients. Low level of PDZK1 in both mRNA and protein was associated with reduced overall survival (OS) and disease-free survival (DFS) in two independent sets. In univariate and multivariate analyses, PDZK1 was defined as an independent prognostic factor for both OS and DFS. These findings indicated that low level of PDZK1 could predict poor clinical outcome in patients with ccRCC.

Koehler P, Hamprecht A, Bader O, et al.
Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study.
Int J Antimicrob Agents. 2017; 49(2):218-223 [PubMed] Related Publications
Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently.

Tesson S, Richards I, Porter D, et al.
Women's preferences for contralateral prophylactic mastectomy following unilateral breast cancer: What risk-reduction makes it worthwhile?
Breast. 2017; 31:233-240 [PubMed] Related Publications
OBJECTIVES: Contralateral prophylactic mastectomy (CPM) reduces the risk of contralateral breast cancer (BC) following unilateral BC, but may not increase survival in BRCA1/2 mutation negative women. Despite this, and the risk for adverse physical and psychological impact, uptake is increasing in BRCA1/2 mutation negative women. We aimed to quantify the degree of reduction in lifetime contralateral BC risk women required to justify CPM, and to explore demographic, disease and psychosocial predictors of preferences using Protection Motivation Theory (PMT) as a theoretical framework. Reasoning behind preferences was also examined.
MATERIALS AND METHODS: 388 women previously diagnosed with unilateral BC, of negative or unknown BRCA1/2 status, were recruited from an advocacy group research database. Two hypothetical risk trade-off scenarios were used to quantify the reduction in lifetime contralateral BC risk that women judged necessary to justify CPM, using a 5% and 20% baseline. Demographic, disease and PMT measures were assessed using a questionnaire.
RESULTS: Most women required their risk to be more than halved from a 5% or 20% baseline to justify CPM. Polarised preferences were also common, with some women consistently accepting or refusing CPM independent of risk/benefit trade-offs. Preferences were associated with coping self-efficacy and having a prior CPM. Explanations for judging CPM worthwhile included reducing or eliminating contralateral BC risk, attaining breast symmetry and reducing worry.
CONCLUSION: Risk-reduction preferences were highly variable. Decisive factors in women's preferences for CPM related to clinical, psychological and cosmetic outcomes, but not to demographic or disease characteristics.

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