Prevalence of targetable genomic alterations in young women with advanced breast cancer: a cross-sectional study.

PURPOSE: Approximately 5% of breast cancers each year are diagnosed in young women < 40 years who tend to have worse clinical outcomes. We compared genomic alterations using comprehensive genomic profiling (CGP) of tumor tissue among very young women (< 30 years) and young women (30-39 years) compared to women ≥ 40 years at diagnosis. METHODS: 2049 advanced breast cancer cases were submitted to Foundation Medicine within a 22-month window for CGP. Hybrid-capture based CGP was performed to evaluate all classes of genomic alterations. Tumor mutational burden was determined on at least 0.8 Mbp of sequenced DNA and microsatellite instability was determined on at least 95 loci. Immunocyte PD-L1 expression was determined by immunohistochemistry. RESULTS: Of the total cases, 28 (1.37%) were < 30 years, 159 (7.76%) were 30-39 years, and 1862 (90.87%) were ≥ 40 at time of diagnosis. Breast tumors were less likely to be estrogen receptor positive in younger women (54% of < 30 years, p > 0.05; 60% of 30-39 years, p < 0.001; 69.4% of ≥ 40 years) and more likely to be triple negative (43%, p = 0.05; 33%, p = 0.05; 26.1% respectively). Young women had higher rates of BRCA1 mutations (17.9% <30 years, p < 0.001; 10.1% 30-39 years, p < 0.001; 2.6% ≥40 years), but lower rates of CDH1 (7.1% <30 years, p > 0.05; 5.0% 30-39 years, p < 0.001; 15.4% ≥40 years) and PIK3CA mutations (17.9% <30 years, p = 0.02; 17.6% 30-39 years, p < 0.001; 40.0% ≥40 years). CONCLUSION: Our findings contribute to the growing literature demonstrating unique genetic profiles among young women diagnosed with breast cancer, compared to older women.

Targeted proteomic scan identifies alteration of serum proteins among workers occupationally exposed to low levels of trichloroethylene.

Occupational exposure to trichloroethylene (TCE) has been associated with alterations in B-cell activation factors and an increased risk of non-Hodgkin's lymphoma (NHL). Here, we aimed to examine the biological processes influenced by TCE exposure to understand the underlying molecular mechanisms. This cross-sectional molecular epidemiology study included data of 1317 targeted proteins in the serum from 42 TCE exposed and 34 unexposed factory workers in Guangdong, China. We used multivariable linear regressions to identify proteins associated with TCE exposure and examined their exposure-response relationship across categories of TCE exposure (unexposed, low exposed: <10 ppm, high exposed: ≥10 ppm). We further examined pathway enrichment of TCE-related proteins to understand their biological response. Occupational exposure to TCE was associated with lower levels of tumor necrosis factor receptor superfamily member 17 (TNFRSF17; ß = -.08; p-value = .0003) and kynureninase (KYNU; ß = -.10, p-value = .002). These proteins also showed a significant exposure-response relation across the unexposed, low exposed, and high exposed workers (all p-trends < .001, false discovery rate [FDR] < 0.20). Pathway analysis of TCE-related proteins showed significant enrichment (FDR < 0.05) for several inflammatory and immune pathways. TCE exposure was associated with TNFRSF17, a key B-cell maturation antigen that mediates B-cell survival and KYNU, an enzyme that plays a role in T-cell mediated immune response. Given that altered immunity is an established risk factor for NHL, our findings support the biological plausibility of linking TCE exposure with NHL.

Racial and ethnic differences in all-cause mortality among Hispanics diagnosed with follicular lymphoma and chronic lymphocytic leukemia in the Bronx, NY.

PURPOSE: Research suggests better survival among Hispanics with diffuse large B-cell lymphoma (DLBCL) compared to non-Hispanic Whites (NHW); however, less is known about racial/ethnic survival differences in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). METHODS: We identified incident FL and CLL cases diagnosed between 2005 and 2016 at Montefiore Medical Center in the Bronx, NY. Cox proportional hazards regression assessed the association between race/ethnicity and all-cause mortality among FL and CLL separately. RESULTS: Of the 201 FL patients, 39.3% were NHW, 19.4% non-Hispanic Black (NHB), and 41.3% Hispanic, with a similar distribution among CLL patients. After adjusting for International Prognostic Index factors, sex, and chemotherapy, Hispanics with FL had lower all-cause mortality compared to NHWs (HR = 0.22; 95% CI 0.08-0.63), similar to prior DLBCL findings. All-cause mortality did not differ between NHBs and NHWs for FL or by any race/ethnicity for CLL. CONCLUSION: In our diverse, urban population, we found that Hispanic diagnosed with FL had lower all-cause mortality compared to NHWs. We found no significant difference in all-cause mortality between Hispanics and NHWs diagnosed with CLL. Our study adds to the growing literature on racial and ethnic differences in survival among Hispanics with hematologic malignancies.

Racial and ethnic differences in diffuse large B-cell lymphoma survival among an underserved, urban population.

Racial/ethnic differences in diffuse large B-cell lymphoma (DLBCL) survival have focused on non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB), often excluding Hispanics/Latinos. To further assess these racial/ethnic survival differences, we identified incident DLBCL cases diagnosed between 2005 and 2016 (n = 404; NHW = 136, NHB = 106, Hispanic/Latino = 162) at Montefiore Medical Center (Bronx, NY). All-cause mortality survival curves were assessed by the Kaplan-Meier method and log-rank test. Cox proportional hazards regression assessed the association between demographic/clinical factors and all-cause mortality. Hispanic/Latino patients experienced 52% lower risk of mortality compared to NHWs (HR = 0.48, 95%CI = 0.28-0.83), after adjusting for clinical prognostic factors. This reduced risk experienced by Hispanics/Latinos was similarly observed by age at diagnosis (≤60 years, >60 years), stage (I/II, III/IV), and receipt of chemotherapy. NHBs and NHWs experienced similar risk of mortality (HR = 0.85, 95%CI = 0.52-1.40). Overall, among DLBCL patients, Hispanics/Latinos had improved survival compared to NHWs. Additional research should seek to identify the drivers of this survival benefit.

Environmental health literacy and household air pollution-associated symptoms in Kenya: a cross-sectional study.

BACKGROUND: Household air pollution (HAP) is a significant source of the global burden of disease. Our objective was to evaluate the association between environmental health literacy (EHL), a domain of health literacy (HL) that describes the ability to use environmental health information to reduce health risks, and symptoms associated with HAP. METHODS: We performed a cross-sectional population-based study of 353 households in Kasarani, Kenya. One individual from each household was surveyed using our novel EHL survey tool. Baseline characteristics were compared between individuals who were symptomatic (i.e., experiencing cough, shortness of breath, phlegm production, wheeze, chest tightness, headache, eye irritation, or burns from cooking at least 5 times per month) versus individuals who were asymptomatic (i.e., experiencing none or symptoms no more than once per month). Multivariate logistic regression was used to determine the odds ratios (OR) of self-reported symptoms associated with HL, stratified by median EHL, adjusting for education, self-perceived health and solid fuel use. RESULTS: A total of 100 individuals (28%) reported experiencing one or more symptoms at least 5 times per month, including 31.2% of solid fuel users and 30.3% of non-solid fuel users. Among individuals with high EHL, higher HL was associated with lower risk of experiencing symptoms (OR = 0.26; 95% CI 0.10-0.67), however, there was no association among individuals with low EHL (OR = 0.85; 95% CI 0.34-2.13). Among solid fuel users, the association between HL and risk of experiencing symptoms was driven by individuals with high EHL (OR = 0.30; 95% CI 0.05-1.84), rather than those with low EHL (OR = 1.22; 95% CI 0.36-4.16). CONCLUSIONS: To the best of our knowledge, this was the first study to assess the association between EHL, HL, and HAP-associated symptoms. Our findings highlight the potential importance of EHL in promoting sustainable interventions to reduce symptoms associated with HAP from solid fuel use among communities in Kenya.

Influence of Rurality, Race, and Ethnicity on Non-Hodgkin Lymphoma Incidence.

INTRODUCTION: Exposure to lymphomagens vary by geography. The extent to which these contribute to racial and ethnic disparities in non-Hodgkin lymphoma (NHL) incidence is not well understood. We sought to evaluate the association between urban-rural status and racial and ethnic disparities in the 3 major NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We used data on NHL incidence from 21 Surveillance, Epidemiology, and End Results (SEER) population-based registries for the period 2000 to 2016. Population characteristics were compared by NHL subtype and urban-rural status, using rural-urban continuum codes from the US Department of Agriculture. Incidence rate ratios were calculated, and Poisson regression was used to assess the association between incidence and rurality. RESULTS: A total of 136,197 DLBCL, 70,882 FL, and 120,319 CLL incident cases aged ≥ 20 years were reported. The majority of DLBCL patients were non-Hispanic white (73.5%), with 11.9% Hispanic and 7.3% non-Hispanic black, with a similar distribution observed in FL and CLL. Adjusting for age, sex, and family poverty, we found increased DLBCL incidence among Hispanics in increasingly urban areas compared to rural areas (rural incidence rate ratio [IRR] = 1.00; nonmetropolitan urban IRR = 1.32, 95% CI 1.16, 1.51; metropolitan urban IRR = 1.55, 95% CI 1.36, 1.76). Among non-Hispanic blacks, urban areas, relative to rural areas, were associated with increased CLL incidence (IRR = 1.48; 95% CI 1.27, 1.72). CONCLUSION: Urban-rural incidence patterns suggest that environmental exposures in urban areas associated with DLBCL and CLL pathogenesis may disproportionately affect Hispanics and non-Hispanic blacks.

PRDM15 Is Associated with Risk of Chronic Obstructive Pulmonary Disease in a Rural Population in Chile.

BACKGROUND: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with ∼1% of Latin American ancestry. OBJECTIVE: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. METHOD: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p ≤ 0.001), call rates (<95%), and minor allele frequencies (<0.5%) in controls, 455,564 markers were available for logistic regression. RESULTS: PRDM15 rs1054761 C allele (p = 2.22 × 10-7) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10-6). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. CONCLUSION: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.

Spread of academic success in a high school social network.

Application of social network analysis to education has revealed how social network positions of K-12 students correlate with their behavior and academic achievements. However, no study has been conducted on how their social network influences their academic progress over time. Here we investigated correlations between high school students' academic progress over one year and the social environment that surrounds them in their friendship network. We found that students whose friends' average GPA (Grade Point Average) was greater (or less) than their own had a higher tendency toward increasing (or decreasing) their academic ranking over time, indicating social contagion of academic success taking place in their social network.