Disparities in cancer genetics care by race/ethnicity among pan‐cancer patients with pathogenic germline variants

Liu, Ying L.; Maio, Anna; Kemel, Yelena; Salo‐Mullen, Erin; Sheehan, Margaret; Tejada, Prince Ray; Trottier, Magan; Arnold, Angela G.; Fleischut, Megan Harlan; Latham, Alicia; Carlo, Maria I.; Murciano‐Goroff, Yonina R.; Walsh, Michael F.; Mandelker, Diana; Mehta, Nikita; Bandlamudi, Chaitanya; Arora, Kanika; Zehir, Ahmet; Berger, Michael F.; Solit, David B.; Aghajanian, Carol; Díaz, Luis A.; Brown, Carol L.; Offit, Kenneth; Hamilton, Jada G.; Stadler, Zsofia K.

doi:10.1002/cncr.34434

Cited by 18 publications

(18 citation statements)

References 58 publications

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“…Self‐reported data on race/ethnicity and AJ ancestry were used to classify patients into mutually exclusive ancestry groups: NH‐White, AJ, non‐White (Asian, Black/AA, Hispanic, or Other), or unknown. All patients self‐identifying as AJ or Hispanic were classified as such, regardless of race, and all patients identifying as American Indian/Alaskan Native, Native Hawaiian, or Other Pacific Islander were classified as Other, as previously described 24 …”

Section: Methodsmentioning

confidence: 99%

“…Disparities in referral/uptake for genetic counseling, completion of genetic testing, and subsequent utilization of cancer screening and prevention by race/ethnicity, which affect not only patients but their families, are well characterized in the hereditary breast and ovarian cancer literature 19–21 . Across cancer types, in patients who undergo paired somatic/germline assessment as part of routine oncologic care (mainstreaming), 22,23 self‐identified Black/AA patients are less likely to undergo recommended counseling for germline findings compared with non‐Hispanic (NH) White patients 24 . However, there is a lack of data regarding racial/ethnic disparities in relation to genetic testing and follow‐up specifically in patients with EC, a cancer type in which racial disparities in outcomes are particularly stark 25 …”

Section: Introductionmentioning

confidence: 99%

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Pathogenic germline variants in patients with endometrial cancer of diverse ancestry

Liu,

Gordhandas,

Arora

et al. 2023

Cancer

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BackgroundRacial disparities in outcomes exist in endometrial cancer (EC). The contribution of ancestry‐based variations in germline pathogenic variants (gPVs) is unknown.MethodsGermline assessment of ≥76 cancer predisposition genes was performed in patients with EC undergoing tumor‐normal Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets sequencing from January 1, 2015 through June 30, 2021. Self‐reported race/ethnicity and Ashkenazi Jewish ancestry data classified patients into groups. Genetic ancestry was inferred from Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets. Rates of gPV and genetic counseling were compared by ancestry.ResultsAmong 1625 patients with EC, 216 (13%) had gPVs; 15 had >1 gPV. Rates of gPV varied by self‐reported ancestry (Ashkenazi Jewish, 40/202 [20%]; Asian, 15/124 [12%]; Black/African American (AA), 12/171 [7.0%]; Hispanic, 15/124 [12%]; non‐Hispanic (NH) White, 129/927 [14%]; missing, 5/77 [6.5%]; p = .009], with similar findings by genetic ancestry (p < .001). We observed a lower likelihood of gPVs in patients of Black/AA (odds ratio [OR], 0.44; 95% CI, 0.22–0.81) and African (AFR) ancestry (OR, 0.42; 95% CI, 0.18–0.85) and a higher likelihood in patients of Ashkenazi Jewish genetic ancestry (OR, 1.62; 95% CI; 1.11–2.34) compared with patients of non‐Hispanic White/European ancestry, even after adjustment for age and molecular subtype. Somatic landscape influenced gPVs with lower rates of microsatellite instability‐high tumors in patients of Black/AA and AFR ancestry. Among those with newly identified gPVs (n = 114), 102 (89%) were seen for genetic counseling, with lowest rates among Black/AA (75%) and AFR patients (67%).ConclusionsIn those with EC, gPV and genetic counseling varied by ancestry, with lowest rates among Black/AA and AFR patients, potentially contributing to disparities in outcomes given implications for treatment and cancer prevention.Plain Language Summary Black women with endometrial cancer do worse than White women, and there are many reasons for this disparity. Certain genetic changes from birth (mutations) can increase the risk of cancer, and it is unknown if rates of these changes are different between different ancestry groups. Genetic mutations in 1625 diverse women with endometrial cancer were studied and the lowest rates of mutations and genetic counseling were found in Black and African ancestry women. This could affect their treatment options as well as their families and may make disparities worse.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pathogenic germline variants in patients with endometrial cancer of diverse ancestry

Liu,

Gordhandas,

Arora

et al. 2023

Cancer

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“…Understanding diverse perspectives regarding the personal utility of genetics and genomics could help improve recruitment of diverse populations for clinical genomics research 10 and increase uptake of clinical genetic testing among currently underrepresented demographic groups. 11 Although previous reviews have described the literature on personal utility, these studies have not reported the demographic characteristics of participants included in the reviewed studies. 1,3 To address this gap, we conducted a systematic review of the peer-reviewed literature focused on defining and measuring the personal utility of genetic and genomic testing to determine the underlying demographic characteristics of study participants.…”

Section: Introductionmentioning

confidence: 99%

“…The need to diversify genomic data sets is widely recognized, but the parallel challenge of including diverse participants in studies of the perceived value of genetic and genomic testing remains relatively unexplored. Understanding diverse perspectives regarding the personal utility of genetics and genomics could help improve recruitment of diverse populations for clinical genomics research and increase uptake of clinical genetic testing among currently underrepresented demographic groups …”

Section: Introductionmentioning

confidence: 99%

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Demographic Characteristics Associated With Perceptions of Personal Utility in Genetic and Genomic Testing

et al. 2023

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ImportanceThe expansion of genetic and genomic testing in health care has led to recognition that these tests provide personal as well as clinical utility to patients and families. However, available systematic reviews on this topic have not reported the demographic backgrounds of participants in studies of personal utility, leaving generalizability unclear.ObjectiveTo determine the demographic characteristics of participants in studies examining the personal utility of genetic and genomic testing in health care.Evidence ReviewFor this systematic review, we utilized and updated the results of a highly cited 2017 systematic review on the personal utility of genetics and genomics, which identified relevant articles published between January 1, 2003, and August 4, 2016. We also used the original methods to update this bibliography with literature published subsequently up to January 1, 2022. Studies were screened for eligibility by 2 independent reviewers. Eligible studies reported empirical data on the perspectives of patients, family members, and/or the general public in the US on the personal utility of any type of health-related genetic or genomic test. We utilized a standardized codebook to extract study and participant characteristics. We summarized demographic characteristics descriptively across all studies and by subgroup based on study and participant characteristics.FindingsWe included 52 studies with 13 251 eligible participants. Sex or gender was the most frequently reported demographic characteristic (48 studies [92.3%]), followed by race and ethnicity (40 studies [76.9%]), education (38 studies [73.1%]), and income (26 studies [50.0%]). Across studies, participants disproportionately were women or female (mean [SD], 70.8% [20.5%]), were White (mean [SD], 76.1% [22.0%]), had a college degree or higher (mean [SD], 64.5% [19.9%]), and reported income above the US median (mean [SD], 67.4% [19.2%]). Examination of subgroups of results by study and participant characteristics evidenced only small shifts in demographic characteristics.Conclusions and RelevanceThis systematic review examined the demographic characteristics of individual participants in studies of the personal utility of health-related genetic and genomic testing in the US. The results suggest that participants in these studies were disproportionately White, college-educated women with above-average income. Understanding the perspectives of more diverse individuals regarding the personal utility of genetic and genomic testing may inform barriers to research recruitment and uptake of clinical testing in currently underrepresented populations.

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Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing

Chen,

Facio,

Aradhya

et al. 2023

JAMA Netw Open

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ImportanceVariants of uncertain significance (VUSs) are rampant in clinical genetic testing, frustrating clinicians, patients, and laboratories because the uncertainty hinders diagnoses and clinical management. A comprehensive assessment of VUSs across many disease genes is needed to guide efforts to reduce uncertainty.ObjectiveTo describe the sources, gene distribution, and population-level attributes of VUSs and to evaluate the impact of the different types of evidence used to reclassify them.Design, Setting, and ParticipantsThis cohort study used germline DNA variant data from individuals referred by clinicians for diagnostic genetic testing for hereditary disorders. Participants included individuals for whom gene panel testing was conducted between September 9, 2014, and September 7, 2022. Data were analyzed from September 1, 2022, to April 1, 2023.Main Outcomes and MeasuresThe outcomes of interest were VUS rates (stratified by age; clinician-reported race, ethnicity, and ancestry groups; types of gene panels; and variant attributes), percentage of VUSs reclassified as benign or likely benign vs pathogenic or likely pathogenic, and enrichment of evidence types used for reclassifying VUSs.ResultsThe study cohort included 1 689 845 individuals ranging in age from 0 to 89 years at time of testing (median age, 50 years), with 1 203 210 (71.2%) female individuals. There were 39 150 Ashkenazi Jewish individuals (2.3%), 64 730 Asian individuals (3.8%), 126 739 Black individuals (7.5%), 5539 French Canadian individuals (0.3%), 169 714 Hispanic individuals (10.0%), 5058 Native American individuals (0.3%), 2696 Pacific Islander individuals (0.2%), 4842 Sephardic Jewish individuals (0.3%), and 974 383 White individuals (57.7%). Among all individuals tested, 692 227 (41.0%) had at least 1 VUS and 535 385 (31.7%) had only VUS results. The number of VUSs per individual increased as more genes were tested, and most VUSs were missense changes (86.6%). More VUSs were observed per sequenced gene in individuals who were not from a European White population, in middle-aged and older adults, and in individuals who underwent testing for disorders with incomplete penetrance. Of 37 699 unique VUSs that were reclassified, 30 239 (80.2%) were ultimately categorized as benign or likely benign. A mean (SD) of 30.7 (20.0) months elapsed for VUSs to be reclassified to benign or likely benign, and a mean (SD) of 22.4 (18.9) months elapsed for VUSs to be reclassified to pathogenic or likely pathogenic. Clinical evidence contributed most to reclassification.Conclusions and RelevanceThis cohort study of approximately 1.6 million individuals highlighted the need for better methods for interpreting missense variants, increased availability of clinical and experimental evidence for variant classification, and more diverse representation of race, ethnicity, and ancestry groups in genomic databases. Data from this study could provide a sound basis for understanding the sources and resolution of VUSs and navigating appropriate next steps in patient care.

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Disparities in cancer genetics care by race/ethnicity among pan‐cancer patients with pathogenic germline variants

Cited by 18 publications

References 58 publications

Pathogenic germline variants in patients with endometrial cancer of diverse ancestry

Pathogenic germline variants in patients with endometrial cancer of diverse ancestry

Demographic Characteristics Associated With Perceptions of Personal Utility in Genetic and Genomic Testing

Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing

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