Breast cancer (BC) is potentially a traumatic stressor which may be associated with negative outcomes, such as post-traumatic stress disorder (PTSD) or positive changes, such as post-traumatic growth (PTG). This study aims to identify the core issues of BC related PTSD, PTG and psychological distress by interrogating the literature in BC survivors. We have also highlighted issues related to the assessment, diagnosis and clinical management of PTSD and PTG. The authors systematically reviewed studies published from 1985 to 2014 pertaining to PTSD, psychological distress and PTG in BC survivors with particular attention paid to incidence rates and causative factors. Multiple studies intimated that women with BC have evidence of PTSD at the initial stages of diagnosis, whereas PTG develops once patients undergo treatment. Early diagnosis and treatment of PTSD/PTG is paramount from literature review but the previously mentioned relationship between PTSD and PTG in BC patients could not be verified. It is evident from the literature that a small percentage of BC patients experience PTSD, while the majority experience PTG after BC diagnosis and treatment. Future research should include prospective studies focusing on high-risk patients, causative factors and the development of psychological interventions.
Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.
CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7 Ã 1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P ¼ 0.03), all-cause mortality in lung cancer patients (HR, 1.43; P ¼ 0.009), and CLL progression (HR, 1.62; P ¼ 0.03). We also found borderline evidence of a statistical interaction between the CYP3A7 Ã 1C allele, treatment of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (P interaction ¼ 0.06). The CYP3A7 Ã 1C allele, which results in adult expression of the fetal CYP3A7 gene, is likely to be the functional allele influencing levels of circulating endogenous sex hormones and outcome in these various malignancies. Further studies confirming these associations and determining the mechanism by which CYP3A7 Ã 1C influences outcome are required. One possibility is that standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximately 8% of cancer patients who are CYP3A7 Ã 1C carriers.
Background MicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients. Materials and Methods All studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size. Result Thirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39–1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: <0.001% and P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, <0.001 and 61.28%, 0.006, respectively). These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-let-7 were associated with poor prognosis in NSCLC. Conclusion miR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.
Aims: In the Northern Territory (NT) of Australia, Indigenous women have a lower incidence of breast cancer, but a higher mortality than Non-indigenous women. The aim of this study was to describe and compare breast cancer pathological features related to stage and biological aggression between the two groups. Methods: Subjects were identified by extract from the NT Cancer Registry in two separate cohorts, cohort 1 (1991-2000) and cohort 2 (2001-2010). Data from cohort 1 included age, stage, tumor grade and estrogen receptor status (ER) and treatment completion. Additional pathological variables including tumor size, HER2 status, lymphovascular invasion and derived tumor phenotype were available for cohort 2. Bivariate P values for categoric variables were calculated using Fisher's exact tests. The Wilcoxon rank-sum test was used to compare cohort 2. Logistic regression was used to calculate odds ratios. Results: There were 359 (44 indigenous) eligible women in cohort 1 and 526 (100 indigenous) for cohort 2. In cohort 1, in both cohorts, indigenous women were more likely to present at an advanced stage, but there was no difference in ER status or tumor grade. When derived phenotypes were compared, indigenous women were less likely to have better prognosis luminal A tumors, and more likely to have HER2-enriched tumors. Conclusion: This two decade long comparison of the pathological features of breast cancer between indigenous and nonindigenous women of the NT has confirmed that Indigenous women not only present at a later stage than NI women but are also afflicted by poorer prognosis tumors, particularly HER2 enriched.
Prostate cancer (PC) is a common cancer (excluding non-melanoma skin cancer) in men in many parts of the world, although incidence and mortality rates vary significantly by population. In current medical practice, prognostic markers for PC include the presenting serum prostate-specific antigen (PSA) level, tumour Gleason score (GS) and clinical tumour stage. However, existing pre-treatment factors cannot be used to predict acute radiotherapy (RT)-induced toxicity. Therefore, new protein biomarkers are required in RT oncology to improve decision-making, treatment and therapy monitoring for PC patients. The aim of this systematic review is to the update potential research to address the difference in cytokine expression and their association with RT-induced toxicity and clinical outcomes. Studies were collected after searching three electronic databases: PubMed, Medline, and Google Scholar. An additional search was carried out through cross-check on a bibliography of selected articles. After the selection process made by two of the authors, 19 articles met the inclusion criteria and were included in the systematic review. Results from previous studies identified elevated levels of cytokines have been reported in several types of cancers and have sometimes correlated with disease progression or prognosis. Elevated levels of cytokine were noticed after immediate exposure to RT and their association with RT-induced acute/late toxicity of PC patients. Moreover, above studies also identified overexpression of cytokines on tumour biopsies and correlation with shortening cancer-specific survival and biochemical recurrence. Thus, altered levels of cytokine might be predictive biomarkers for RT-induced and clinical outcomes of PC patients.
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