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This study aimed to verify whether germline single nucleotide variants (SNV) in CTLA-4 gene, c.-1765C>T, c.-1661A>G, c.-1577G>A, and c.-1478G>A, influence the risk, clinicopathological aspects, and survival of patients with CM, as well as its functional consequences. A total of 432 patients with CM and 504 controls were evaluated. CTLA-4 genotypes were identified by real-time polymerase chain reaction (RT-PCR) and expression of CTLA-4 by quantitative PCR (qPCR) and luciferase assay. Cell cycle, proliferation, apoptosis/necrosis, and migration analyses were performed in SK-MEL-28 and A-375 cell lines modified to present homozygous ancestral or variant genotypes by CRISPR technique. Individuals with the CTLA-4 c.-1577 AA genotype and the combined CTLA-4 c.-1577 and c.-1478 AA + AA genotypes were at 1.60- and 3.12-fold higher risk of developing CM, respectively. The CTLA-4 c.-1577 AA genotype was seen as an independent predictor of worse event-free survival and was also associated with higher gene expression, higher cell proliferation, lower cell apoptosis, and higher cell migration. Our data present, for the first time, evidence that CTLA-4 c.-1577G>A alters the risk and clinical aspects of CM treated with conventional procedures and may be used for selecting individuals for tumor prevention and patients for distinct treatment. [ABSTRACT FROM AUTHOR]

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3′-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3′-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients. [ABSTRACT FROM AUTHOR]

Ultraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele "A" were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3, CREB1, and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients' clinicopathological features. [ABSTRACT FROM AUTHOR]

Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients. [ABSTRACT FROM AUTHOR]

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Background: Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods: This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2/df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results: Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2/df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). The model exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2: λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2: λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2: λ: p = .058; i: p < .001; Res: p < .001). Conclusion: The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatments. [ABSTRACT FROM AUTHOR]

Background: The psychometric properties of an instrument should be evaluated routinely when using different samples. This study evaluated the psychometric properties of the Functional Assessment of Cancer Therapy-General (FACT-G) when applied to a sample of Brazilian cancer patients.Methods: The face, content, and construct (factorial, convergent, and discriminant) validities of the FACT-G were estimated. Confirmatory factor analysis (CFA) was conducted the ratio chi-square by degrees of freedom (χ (2)/df), the comparative fit index (CFI), the Tucker-Lewis index (TLI), and the root mean square error of approximation (RMSEA) as indices. The invariance of the best model was assessed with multi-group analysis using the difference of chi-squares method (Δχ(2)). Convergent validity was assessed using Average Variance Extracted (AVE) and discriminant validity was determined via correlational analysis. Internal consistency was assessed using the Cronbach's alpha (α) coefficient, and the Composite Reliability (CR) was estimated.Results: A total of 975 cancer patients participated in the study, with a mean age of 53.3 (SD = 13.0) years. Of these participants, 61.5 % were women. In CFA, five correlations between errors were included to fit the FACT-G to the sample (χ (2)/df = 8.611, CFI = .913, TLI = .902, RMSEA = .088). The model did not indicate invariant independent samples (Δχ(2): μ: p < .001, i: p < .958, Cov: p < .001, Res: p < .001). While there was adequate convergent validity for the physical well-being (AVE = .54) and social and family Well-being factors (AVE = .55), there was low convergent validity for the other factors. Reliability was adequate (CR = .76-.89 and α = .71-.82). Functional well-being, emotional well-being, and physical well-being were the factors that demonstrated a strong contribution to patients' health-related quality of life (β = -.99, .88, and .64, respectively).Conclusion: The FACT-G was found to be a valid and reliable assessment of health-related quality of life in a Brazilian sample of patients with cancer. [ABSTRACT FROM AUTHOR]

Somatic copy number aberrations (CNAs) have been associated with clear-cell renal carcinoma (ccRCC) pathogenesis and are a potential source of new diagnostic, prognostic and therapeutic biomarkers. Recurrent CNAs include loss of chromosome arms 3p, 14q, 9p, and gains of 5q and 8q. Some of these regional CNAs are suspected of altering gene expression and could influence clinical outcomes. Despite many studies of CNAs in RCC, there are currently no descriptions of genomic copy number alterations in a Brazilian ccRCC cohort. This study was designed to evaluate the chromosomal profile of CNAs in Brazilian ccRCC tumors and explore clinical associations. A total of 92 ccRCC Brazilian patients that underwent nephrectomy at Barretos Cancer Hospital were analyzed for CNAs by array comparative genomic hybridization. Most patients in the cohort had early-stage localized disease. The most significant alterations were loss of 3p (87.3%), 14q (35.8%), 6q (29.3%), 9p (28.6%) and 10q (25.0%), and gains of 5q (59.7%), 7p (29.3%) and 16q (20.6%). Bioinformatics analysis revealed 19 genes mapping to CNA significant regions, including SETD2, BAP1, FLT4, PTEN, FGFR4 and NSD1. Moreover, gain of 5q34-q35.3 (FLT4 and NSD1) and loss of 6q23.2-q23.3 (MYB) and 9p21.3 (MLLT3) had gene expression levels that correlated with TCGA data and was also associated with advanced disease features, such as larger tumors, Fuhrman 3, metastasis at diagnosis and death. The loss of region 14q22.1 which encompasses the NIN gene was associated with poor overall survival. Overall, this study provides the first CNA landscape of Brazilian patients and pinpoints genomic regions and specific genes worthy of more detailed investigations. Our results highlight important genes that are associated with copy number changes involving large chromosomal regions that are potentially related to ccRCC tumorigenesis and disease biology for future clinical investigations. [ABSTRACT FROM AUTHOR]