Racial disparities in prevalence of homologous recombination deficiency in ovarian, uterine, and cervical cancer tumors

Abstract

<h3>Objectives:</h3> Prior literature suggests that Black individuals exhibit a higher prevalence of aggressive molecular features in different cancers including endometrial cancers. Blacks may also have more defects in homologous recombination deficiency (HRD). It is currently unclear if the difference in somatic mutations in HRD genes between Blacks and Whites extends to other races and varies by cancer site. This study evaluated racial disparities in somatic mutations in HRD genes in ovarian, endometrial, and cervical cancer. <h3>Methods:</h3> Data were obtained from The Cancer Genome Atlas (TCGA). Somatic mutations in genes associated with HRD including <i>BRCA-1, BRCA-2,</i> PTEN, CDK12, and RAD51C were acquired for the women with invasive ovarian, uterine, or cervical cancer. Race was categorized as White, Black, Asian, American-Indian, Pacific Islander, or Unknown. Chi-square was used to compare differences in the proportion of mutations between racial groups. <h3>Results:</h3> A total of 280 ovarian, 472 uterine, and 139 cervical cancer patients were included in our analysis and the distribution of somatic mutations in five HRD are displayed in Table 1 by topographic site. Within ovarian cancers, <i>BRCA-1</i> was the most common mutation (8.57%), followed by CDK12 (7.50%) and <i>BRCA-2</i> (7.14%). The rate of <i>BRCA-1</i> mutations in Asian, White, and Black individuals was 10.0%, 7.59%, and 6.25%, respectively (<i>P</i>=0.21). In the endometrial cancer cases, 74.6% expressed a PTEN mutation, and 19.3% expressed a <i>BRCA-2</i> mutation. PTEN mutations were less common in Black women (57.3%) compared to Whites (78.3%) or Asians (90.0%) (<i>P</i>=2.19 x10-18). Finally, 25.2% of all cervical cancer tumors expressed the PTEN mutation, with a similar distribution of PTEN mutations in Asians (28.6%), Blacks (26.7%), and Whites (23.4%) (p=0.78). When considering gynecologic malignancies as an integrated group, 21.6% of Asians had somatic mutations in <i>BRCA-1</i> (21.6%) compared to 9.9% in Whites (9.94%) or 7.5% in Blacks (<i>P</i>=0.001). Asians also had the highest proportion of somatic mutations in <i>BRCA-2</i> (24.3%) compared with 13.3% in Whites and 14.2% in Blacks (<i>P</i>=6.62x10^-6). <h3>Conclusions:</h3> The observed racial differences in the distribution of somatic mutations in HRD across gynecologic malignancies merits further investigation to tailor treatment selection to target these defects.