899 Population coverage of HLA-A*02:01, *02:05, *02:06 across selected cancer types in the United States

BackgroundGSK is investigating an autologous TCR T-cell therapy for solid tumors that recognizes the cancer testis antigen, NY-ESO-1, presented on the cancer cell surface by specific HLA-A*02 sub-types. The aim of this study was to estimate the number of patients in the US in 2020 with HLA-A*02 genotype subtypes HLA-A*02:01, 02:05, 02:06 across selected cancer types (invasive lung, ovarian, gastric, esophageal, invasive and in-situ bladder and multiple myeloma), accounting for racial variation.MethodsThis study was carried out in three parts utilizing three national datasets.1. The prevalence of each cancer type was estimated by race utilizing prevalence rates from US Surveillance, Epidemiology, and End Results (SEER) 1975–2018 data.1 2. The US population coverage for the specific HLA-A*02 subtype (%) by race in 2020, was estimated utilizing Hardy Weinberg Principles and allele frequencies extracted from the allele frequency net database (US National Marrow Donor Program (NMDP) population only).2 3. The estimated population coverage for the specific HLA-A*02 subtype expression (%) by cancer subtype, was calculated using US Census (2019) data.3 For the purpose of this analyses, single race population estimates were used. Race was categorized as ‘White’, ‘Black’, ‘Asian/Pacific Islander’, ‘Native American’ and ‘Other’. The Hispanic population was included as a proportion of each category, where appropriate. Limitations include the seven assumptions underlying Hardy-Weinberg equilibrium, which were met, and the assumption that the NMDP, SEER and US Census data are reflective of the US population. Predictive and prognostic clinical characteristics including histological subtypes were not accounted for in this analysis.ResultsAcross selected cancer types, the most prevalent race category was White, reflecting the racial distribution of the US (table 1). Of these cancer types, multiple myeloma and invasive gastric cancer are represented by the lowest proportion of White patients and the highest proportion of Black patients. Results of the HLA sub-type distribution by race are presented in the table below. The overall proportion of patients who are HLA-A*02:01, *02:05 or *02:06 positive is estimated to be between 41.7% (multiple myeloma) and 45.8% (invasive and in-situ bladder) in the US accounting for the racial variations in each cancer type of interest.Abstract 899 Table 1Proportion of patients who are HLA-A*02:01, *02:05, or *02:06 positive by race and cancer subtypeConclusionsThe proportion of patients with specific HLA-A*02 subtypes is similar across selected cancers, accounting for racial variation in the US. Racial variation by cancer type is an important consideration when estimating the size of eligible populations for T-cell therapies requiring specific HLA-A*02 histocompatibility.AcknowledgementsFundingGlaxoSmithKlineReferencesHowlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2018, National Cancer Institute. Bethesda, MD, [https://seer.cancer.gov/csr/1975_2018/], based on November 2020 SEER data submission, posted to the SEER web site, April 2021 (Accessed July 2021).Gonzalez-Galarza FF, McCabe A, Santos EJ, Jones J, Takeshita LY, Ortega-Rivera ND, Del Cid-Pavon GM, Ramsbottom K, Ghattaoraya GS, Alfirevic A, Middleton D, Jones AR. Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools. Nucleic Acids Res 2020;48:D783–8.U S Census Bureau (2011). ACS demographic and housing estimates. [https://data.census.gov/cedsci/table?q=United%20States&g=0100000US&tid=ACSDP1Y2017.DP05&vintage=2017&layer=state&cid=DP05_0001E] (Accessed July 2021).

Are Teachers Biased against Black Children? A Study of Race, Amygdala Volume, and Problem Behaviors

Introduction: While the amygdala has a core role in behaviors, less is known about racial variation in the association between amygdala volume and teachers’ behavioral rating of children. According to the Minorities’ Diminished Returns (MDRs) phenomenon, the effects of individual-level risk and protective factors tend to be weaker for Black than White children due to structural factors such as social stratification and racism. Purpose: Built on the MDRs framework and conceptualizing race as a social rather than a biological factor, this study explored racial variation in the magnitude of the effects of amygdala volume on teachers’ behavioral ratings of children. Methods: For this cross-sectional study, we used baseline socioeconomic data and structural magnetic resonance imaging (sMRI) data of 4305 American children ages 9-10 who had participated in the Adolescent Brain Cognitive Development (ABCD) study. The primary outcome was the teachers’ behavioral rating of the child. The independent variable was amygdala volume. Age, sex, parental education, parental marital status, and ethnicity were the covariates. Race was the moderator. We used mixed-effect models for data analysis to adjust for the participants’ nested nature within families and study sites. Results: Teachers rated children with larger amygdala volumes as having lower behavioral problems. The concordance between size of amygdala volume and teachers’ behavioral rating of the child was modified by race. For while children, teachers reported the children to have lower behavioral problems when they had a large amygdala. For Black children, teachers reported high behavioral problems across all amygdala sizes. Conclusions: The results can be explained in two ways. The first explanation is minorities’ diminished returns hypothesis (MDRs). In line with MDRs, due to structural inequalities and school segregation, a large amygdala would result in a more favorable behavioral rating of the White children than Black children, as we expect an unequal effect of equal resources across racial groups in the presence of racism. The second explanation is systemic bias of teachers against Black children: meaning that due to their anti-Black bias, teachers report high behavioral problems in Black children, across all amygdala sizes (behavioral profiles). That means, race may trigger some cues and biases in the teachers, so they do not pay attention to the details of the behavioral profile of the Black child. For White children, however, in the absence of such racial bias, teachers behavioral rating of a child reflects the child’s amygdala size.