Biology subjects

Fejerman, L.

Publications and source records attributed to Fejerman, L..

4 recordsLinked to original sources

bioRxiv2022

Profile of the somatic mutational landscape in breast tumors from Hispanic/Latina women

Breast cancer causes the most cancer deaths among Hispanic/Latinas (H/L). However, limited tumor-sequencing data from H/L are available to guide treatment. To address this gap, we performed whole-exome sequencing of DNA from 140 HL germline and 146 matched breast tumors and RNA-seq for the tumors. We generated somatic-mutation profiles, identified copy-number alterations (CNAs), and compared results to non-Hispanic White (White) women in The Cancer Genome Atlas. Similar to Whites, PIK3CA and TP53 were the most commonly mutated genes in breast tumors from H/L. We found 4 common COSMIC mutation signatures (1, 2, 3, 13) and signature 16 not previously reported in other breast-cancer datasets. We observed recurrent amplifications in breast-cancer drivers including MYC, FGFR1, CCND1, and ERBB2, and a recurrent amplification on 17q11.2 associated with high KIAA0100 gene expression, implicated in breast-cancer aggressiveness. Expanded research is required to determine how these characteristics of H/L tumors impact treatment response and survival.

cancer biology↗

bioRxiv2019

A polygenic risk score for breast cancer in U.S. Latinas and Latin-American women

BackgroundOver 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Since most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry.\n\nMethodsWe conducted a pooled case-control analysis of U.S. Latinas and Latin-American women (4,658 cases, 7,622 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (p < 5 x 10-8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression and assessed discrimination using area under the receiver operating characteristic curve (AUROC). We also assessed PRS performance across quartiles of Indigenous American genetic ancestry.\n\nResultsOf 180 SNPs tested, 142 showed directionally consistent associations compared with European populations, and 39 were nominally significant (p < 0.05). The PRS was associated with breast cancer risk, with an odds ratio (OR) per standard deviation increment of 1.58 (95% CI 1.52 to 1.64) and AUCROC of 0.63 (95% CI 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry.\n\nConclusionsThe 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry.

epidemiology↗

bioRxiv2018

Identification of Novel Common Breast Cancer Risk Variants in Latinas at the 6q25 Locus

Background: Breast cancer is a partially heritable trait and over 180 common genetic variants have been associated with breast cancer in genome wide association studies (GWAS). We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25 with the protective minor allele originating from Indigenous American ancestry. Here we report on additional GWAS and replication in Latinas.\n\nMethods: We performed GWAS in 2385 cases and 7342 controls who were either U.S. Latinas or Mexican women. We replicated 2412 cases and 1620 controls of U.S Latina, Mexican, and Colombian women. In addition, we replicated the top novel variants in study of African American and African women and in one study of Chinese women. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model based approach.\n\nResults: We identified 3 SNPs (p=1.9x10-8 - 2.8x10-8) at 6q25 locus not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.75 (0.68-0.83). In a replication in women of Latin American origin, we also observed a consistent effect (OR: 0.88; 95% CI: 0.78-0.99; p=0.037). Since the minor allele was common in East Asians and African American but not European ancestry populations, we replicated in a meta-analysis of those populations and also observed a consistent effect (OR 0.94; 95% CI: 0.91 - 0.97; p=0.013).\n\nConclusion: The effect size of this variant is relatively large compared to other common variants associated with breast cancer and adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

genetics↗

bioRxiv2018

Genetic analysis of Sephardic ancestry in the Iberian Peninsula

The Sephardim are a major Jewish ethnic division whose origins can be traced back to the Iberian Peninsula. We used genome-wide SNP data to investigate the degree of Sephardic admixture in seven populations from the Iberian Peninsula and surrounding regions in the aftermath of their religious persecution starting in the late 14th century. To this end, we used Eastern Mediterranean (from South Italy, Greece and Israel) and North African (Tunisian and Moroccan) populations as proxies for the major ancestral components found in the target populations and carried out unlinked- and linked-marker analyses on the available genetic data. We report evidence of Sephardic ancestry in some of our Iberian samples, as well as in North Italy and Tunisia. We find the Sephardic admixture to be more recent relative to the Berber admixture following an out-of-Iberia geographic dispersal, suggesting Sephardic gene flow from Spain outwards. We also report some of the challenges in assigning Sephardic ancestry to potentially admixed individuals due to the lack of a clear genetic signature.

genomics↗