Search

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9–12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9–12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT–qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9–12 alleles using nanopore long-sequencing. Using the Kruskal–Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9–12 and identifying which of them has developed cancer. [ABSTRACT FROM AUTHOR]

Every year, cancer affects more than one million Latin Americans. The increasing incidence of cancer could be secondary to an aging population, westernization of life style, and urbanization. LA has among the highest incidence rates of gastric cancer, compared to other countries. In this review, different studies on gastric cancer and its relation with risks factors, such as infections, diet and life styles typical of LA, besides the different molecular alterations of that specific population (mainly at a genetic polymorphism level) are analyzed. An exhaustive research was made in PubMed, MEDLINE and Embase of the most relevant studies conducted in the last 27 years (1990–2017) in LA. [ABSTRACT FROM PUBLISHER]

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies. [ABSTRACT FROM AUTHOR]

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case–control study was performed in 49 adult Mexican patients with grade II–IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40–5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17–10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26–4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma. [ABSTRACT FROM AUTHOR]

The deletion of exons 9 to 12 of BRCA1 (9–12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9–12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9–12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9–12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9–12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9–12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9–12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction: Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. Methods: A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. Results: Median follow-up was 41 months (range 1–48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. Conclusions: In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva. [ABSTRACT FROM AUTHOR]

The purpose of this study is to analyze the treatment results of patients with medullary thyroid cancer, focusing on surgical complications, biochemical cures, and survival. It is a retrospective analysis of 18 patients with advanced disease treated in a tertiary, teaching referral hospital in a developing country. Ten patients underwent only a initial surgery, of them, 7 developed surgical complications, 2 of them major. Five patients required a second procedure after the first surgery elsewhere, 2 of them developed complications, one major. Three denied further treatment after diagnosis was made. After a median follow-up of 35.5 months (1-108), 7 (39%) patients are alive without disease, 4 (22%) are alive with disease, and 7 (39%) died. From fifteen patients after surgery with curative puposes, 4 reached normal calcitonin levels and are still without evidence of recurrence after a mean follow-up of 47 months (3-86 months); 11 persisted with disease, of them, five patients needed a second surgery, two of them reached normal calcitonin levels, one of them is still under remission after 36 months, and one died 60 months later. Three patients denied more treatment. Nine patients did not reach normal calcitonin levels after first surgery or reoperation, but on postoperative images there were not evidence of residual disease and 6 of them are alive after a mean follow up of 55 (12-108) months. In conclusion, a biochemical cure for the advanced disease is rare after surgery, however, long term survival is possible when judicious surgery produces no evidence of residual disease by imaging. [ABSTRACT FROM AUTHOR]

Background: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter ( hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. Methods: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. Results: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. Conclusions: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients. [ABSTRACT FROM AUTHOR]

Background and Aims: The rs2981582 single nucleotide polymorphism in the fibroblast growth factor receptor 2 gene has been consistently associated with an increased risk of breast cancer. We evaluated the effect of rs2981582 polymorphism in the FGFR2 gene on the risk of breast cancer and its interaction with non-genetic risk factors. Methods: A population-based case-control study was conducted in Mexico. Data from 687 cases and 907 controls were analyzed. Results: The T allele of the rs2981582 polymorphism was associated with an increased risk of breast cancer (ORper allele = 1.24, 95% CI 1.06–1.46). There was also an interaction between this polymorphism and alcohol consumption (p = 0.043). The effect of alcohol consumption on the risk of breast cancer varied according to the allelic variants of the rs2981582 polymorphism in the FGFR2 gene: OR = 3.97 (95% CI 2.10–7.49), OR = 2.01 (95% CI 1.23–3.29) and OR = 1.21 (95% CI 0.48–3.05) for genotypes CC, CT and TT, respectively. Conclusions: This is the first study exploring the association between rs2981582 polymorphism in the FGFR2 gene and breast cancer risk in Mexican women. The interaction found may be of great public health interest because alcohol consumption is a modifiable breast cancer risk factor. Therefore, replication of this finding is of foremost importance. [Copyright &y& Elsevier]