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Estrogen-receptor-positive (ER+) tumors employ complex signaling that engages in crosstalk with multiple pathways through genomic and non-genomic regulation. A greater understanding of these pathways is important for developing improved biomarkers that can better determine treatment choices, risk of recurrence and cancer progression. Deficiencies in DNA repair capacity (DRC) is a hallmark of breast cancer (BC); therefore, in this work we tested whether ER signaling influences DRC. We analyzed the association between ER positivity (% receptor activation) and DRC in 270 BC patients, then further stratified our analysis by HER2 receptor status. Our results show that among HER2 negative, the likelihood of having low DRC values among ER- women is 1.92 (95% CI: 1.03, 3.57) times the likelihood of having low DRC values among ER+ women, even adjusting for different potential confounders (p<0.05); however, a contrary pattern was observed among HER2 positives women. In conclusion, there is an association between DRC levels and ER status, and this association is modified by HER2 receptor status. Adding a DNA repair capacity test to hormone receptor testing may provide new information on defective DNA repair phenotypes, which could better stratify BC patients who have ER+ tumors. ER+/HER2- tumors are heterogeneous, incompletely defined, and clinically challenging to treat; the addition of a DRC test could better characterize and classify these patients as well as help clinicians select optimal therapies, which could improve outcomes and reduce recurrences.

Background Previous studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC) using a case–control epidemiological study in a Hispanic community. Methods We conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously. Results Compared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels ( p < 0.001). Validity of the association of DRC as a measure of BC risk showed a sensitivity of 83.2% and specificity of 77.6% ( p < 0.0001). Conclusions Our results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.

Efforts for the conservation of the endangered bat species Hipposideros turpis turpis in southern Japan are hampered by a lack of information about its biology and natural history and by the increasing effect of human activities. In an attempt to address some of the conservation challenges faced by this species, we studied the genetic structure and dispersal of intra- and interisland populations using six species-specific microsatellite markers. In particular, we sought to establish the relationship between island populations and to define effective management units for conservation. Pairwise co-ancestry index (F ST) analysis, analysis of molecular variance, and Bayesian clustering suggested the presence of significant genetic differentiation between islands but little differentiation within them. The small Yonaguni Island population appeared to be not only geographically isolated, but also genetically isolated. This population is at the greatest risk of extinction, considering its size and low genetic variation. The larger populations on Iriomote and Ishigaki Islands are genetically related to each other to a greater degree and exhibit higher genetic variation than the Yonaguni Island population. This suggests that these two island populations should be included in a single management unit, while bats from Yonaguni Island should be managed independently and given higher priority for conservation. Actions such as defining vegetation corridors between colonies, as well as building gates at the entrance of the largest known colony, should be included in the conservation agenda of this still poorly known species.

In the setting of total parathyroidectomy and autotransplantation surgery (TPT × AS) as treatment for secondary hyperparathyroidism (SHPT), we evaluated whether intraoperative parathyroid hormone (iPTH) monitoring is useful as a reference for total parathyroid removal. We conducted a prospective, open, single value measurement efficacy study of the intraoperative (i.o.) diagnostic monitoring of iPTH in a cohort of surgical patients. All patients (n = 25) underwent TPT × AS at the Department of Surgery, Donostia Hospital from January 2002 to October 2004. The primary outcome measures were kinetics of serum levels of iPTH during surgery and prediction time of the of descent of PTH levels (measured in the clinic on the day of admission and intraoperatively during induction of anesthesia, every 5 and 10 minutes after removal of the adenoma, and again 24 hours thereafter). iPTH levels returned to normal in all 25 patients, decreasing from pathological levels at the beginning of the operation (1302.24 + 424.9 pg/ml) to half (50%) values at the third intraoperative determination, minute 10 (614.8 ± 196.62), becoming undetectable at 24 hours. Frozen sections were conclusive for parathyroid tissue (20.56 + 10.3 minutes after removal). Intraoperative measurement of iPTH is useful in the prediction complete removal of all parathyroid tissue prior to autotransplantation, thus avoiding persistence of disease because of incomplete surgery.

Inherited pathogenic variants in genes that confer moderate to high risk of breast cancer may explain up to 50% of familial breast cancer. This study aimed at identifying inherited pathogenic variants in breast cancer cases from Puerto Rico that were not linked to BRCA1 or BRCA 2. Forty-eight breast cancer patients that met the clinical criteria for BRCA testing but had received a negative BRCA1 /2 result were recruited. Fifty-three genes previously implicated in hereditary cancer predisposition were captured using the BROCA Agilent cancer risk panel followed by massively parallel sequencing. Missense variants of uncertain clinical significance in CHEK2 were evaluated using an in vitro kinase assays to determine their impact on function. Pathogenic variants were identified in CHEK2 , MUTYH , and RAD51B in four breast cancer patients, which represented 8.3% of the cohort. We identified three rare missense variants of uncertain significance in CHEK 2 and two variants (p.Pro484Leu and p.Glu239Lys) showed markedly decreased kinase activity in vitro comparable to a known pathogenic variant. Interestingly, the local ancestry at the RAD51B locus in the carrier of p.Arg47* was predicted to be of African origin. In this cohort, 12.5% of the BRCA -negative breast cancer patients were found to carry a known pathogenic variant or a variant affecting protein activity. This study reveals an unmet clinical need of genetic testing that could benefit a significant proportion of at-risk Latinas. It also highlights the complexity of Hispanic populations as pathogenic factors may originate from any of the ancestral populations that make up their genetic backgrounds.

The three major hereditary cancer syndromes in Latinos (Hereditary Breast and Ovarian Cancer, Familial Adenomatous Polyposis and Lynch Syndrome) have been shown to exhibit geographic disparities by country of origin suggesting admixture-based disparities. A solid infrastructure of clinical genetics geared towards diagnosis and prevention could aid in reducing the mortality of these cancer syndromes in Latinos. Currently, clinical cancer genetic services in Latin America are scarce. Moreover, limited studies have investigated the mutational spectrum of these cancer syndromes in Latinos resulting in gaps in personalized medicine affecting diagnosis, treatment and prevention. The following commentary discusses available genotype and clinical information on hereditary cancer in Latinos and highlights the limited access for cancer genetic services in Latin America including barriers to genetic testing and alternatives for providing better access to genetic services. In this review, we discuss the status of clinical genetic cancer services for both US Latinos and those Latinos living in Latin America.

Methylation alterations of CpG islands, CpG island shores and first exons are key events in the formation and progression of human cancer, and an increasing number of differentially methylated regions and genes have been identified in breast cancer. Recent studies of the breast cancer methylome using deep sequencing and microarray platforms are providing a novel insight on the different roles aberrant methylation plays in molecular subtypes of breast cancer. Accumulating evidence from a subset of studies suggests that promoter methylation of tumor-suppressor genes associated with breast cancer can be quantified in circulating DNA. However, there is a paucity of studies that examine the combined presence of genetic and epigenetic alterations associated with breast cancer using blood-based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor for breast cancer that has been measured in lymphocytes. We isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL. Methylation of at least one gene was found in 49% of the cases compared to 20% of the controls. Three of the four genes had receiver characteristic operator curve values of ≥0.50: MAL (0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promoter methylation was associated with breast cancer and inversely associated with DRC. This is the first evidence of a significant association between genetic and epigenetic alterations in breast cancer using blood-based tests. The potential diagnostic utility of these biomarkers and their relevance for breast cancer risk prediction should be examined in larger cohorts.

Background In the setting of total parathyroidectomy (TPT) and parathyroid transplantation (PTx) for renal hyperparathyroidism (RHP), we evaluated long‐term parathyroid graft function after subcutaneous pre‐sternal transplantation (SCPTx). Because parathyroid glands are surrounded by fatty tissue, we postulated that results of subcutaneous implantation of parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism could be at least as successful as intramuscular grafting, but without its complications Patients and Methods The study, a prospective open efficacy study of postoperative (po) diagnostic monitoring of intact parathyroid hormone (iPTH) on a cohort of surgical patients, was conducted within a university hospital with a dialysis unit. Thirty five patients (19 women and 16 men) operated on for renal hyperparathyroidism underwent TPT and SCPTx for RHP at the Department of General Surgery and the Department of Nephrology. Donostia Hospital. San Sebastián. Gipuzkoa. Spain, from January 2002 to December 2005. Follow‐up ranges from 6 months to 42 months (median: 15.4 months). The main outcome measure was evaluation of graft function by measurement of iPTH plasma level, based on serum levels of iPTH before operation and 24 h and 1, 3, 5, 15, 30, 60, 100, and 150 weeks after surgery Results Average preoperative iPTH values were 1,341.52 + 367.78 pg/ml (mean ± SD) (range: 493–2,180). After TPT and PSCTx, iPTH levels became undetectable in all patients at 24 h. A level of 50 pg/ml was established as the criterion of adequate parathyroid graft function. Values obtained at the various time intervals were as follows: 14.14 + 7.73 1 pg/ml (mean ± SD) (range: 6–36) after 1 week, 53 + 77.33 pg/ml (mean ± SD) (range: 35–74) after 5 weeks, 62.95 + 20.93 pg/ml (mean ± SD) (range: 11–89) after 15 weeks, 77.54 + 18.84 pg/ml (mean ± SD) (range: 24.6–104.2) after 30 weeks, 109.29 + 50.22 pg/ml (mean ± SD) (range: 54–327) after 60 weeks, 134.21 + 128.64 pg/ml (mean ± SD) (range: 43–712) after 100 weeks, and 122.84 + 117.54 pg/ml (mean ± SD) (range: 68–723) after 150 weeks. Prevalence of hypoparathyroidism (intact parathyroid hormone serum level < 20 pg/ml with a normal or low serum calcium concentration) was 2/35 (5.71%) by week 60 and recovered by week 100. Graft‐related recurrence was 2.85% (1/35). Conclusions Subcutaneous pre‐sternal transplantation (SCPTx) after TPT and PTx for secondary (RHP) is an adequate method to replace muscular forearm parathyroid transplantation and avoid its complications. Functioning results of total parathyroidectomy and presternal subcutaneous grafting compare favorably with the published data on other surgical techniques proposed for the treatment of renal hyperparathyroidism. Results of long‐term follow‐up exceed previously reported results.

Breast cancer is the most common cause of cancer diagnosis in women and is responsible for considerable mortality among the women of Puerto Rico. However, there are few studies in Puerto Rico on the genetic factors influencing risk. To determine the contribution of pathogenic mutations in BRCA1 and BRCA2, we sequenced these genes in 302 cases from two separate medical centers, who were not selected for age of onset or family history. We identified nine cases that are carriers of pathogenic germline mutation. This represents 2.9% of unselected cases and 5.6% of women meeting National Comprehensive Cancer Network (NCCN) criteria for BRCA testing. All of the identified pathogenic mutations were in the BRCA2 gene and the most common mutation is the p.Glu1308Ter (E1308X) mutation in BRCA2 found in eight out of nine cases, representing 89% of the pathogenic carriers. The E1308X mutation has been identified in breast and ovarian cancer families in Spain, and analysis of flanking DNA polymorphisms shows that all E1308X carriers occur on the same haplotype. This is consistent with BRCA2 E1308X being a founder mutation for the Puerto Rican population. These results will contribute to better inform genetic screening and counseling of breast and ovarian cancer cases in Puerto Rico and Puerto Rican populations in mainland United States.

Hereditary cancer predisposition syndromes comprise approximately 10% of diagnosed cancers; however, familial forms are believed to account for up to 30% of some cancers. In Hispanics, the most commonly diagnosed hereditary cancers include colorectal cancer syndromes such as, Lynch Syndrome, Familial Adenomatous Polyposis, and hereditary breast and ovarian cancer syndromes. Although the incidence of hereditary cancers is low, patients diagnosed with hereditary cancer syndromes are at high-risk for developing secondary cancers. Furthermore, the productivity loss that occurs after cancer diagnosis in these high-risk patients has a negative socio-economic impact. This review summarizes the genetic basis, phenotype characteristics, and the National Comprehensive Cancer Network’s screening, testing, and surveillance guidelines for the leading hereditary cancer syndromes. The aim of this review is to promote a better understanding of cancer genetics and genetic testing in Hispanic patients.