Association of Genetic Ancestry with Breast Cancer in Ethnically Diverse Women from Chicago

Abstract

IntroductionNon-Hispanic (nH) Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors.MethodsWe used a panel of 100 ancestry informative markers (AIMs) to estimate individual genetic ancestry in 656 women from the “Breast Cancer Care in Chicago” study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities.ResultsAs expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54–0.92) among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56–0.95) among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02) and higher grade (p = 0.012) in nH Whites and later stage (p = 0.03) in nH Blacks.ConclusionNon-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial/ethnic groups.

Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry

“…An ancestry-specific susceptibility loci on chromosome 8q24.21 has been identified for prostate cancer with a considerably increased frequency in African American men (Bensen et al 2014). In a study of 656 women with breast cancer, higher European genetic contribution was associated with a significantly increased chance of earlier diagnosis (Al-Alem et al 2014).…”

Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans

“…36, 43 These autosomal markers have previously been identified and validated and are used to extract continental ancestry information in admixed populations. 44–46 From a study of over 4,000 autosomal single nucleotide polymorphisms (SNPs) spanning 22 chromosomes, an enriched panel of 100 unlinked AIMs was selected to provide individual ancestry assessment based on several measures of marker informativeness (F ST , F IC , and δ) and confirmed in several parental populations consisting of 60 CEPH Europeans, 56 Yoruban sub-Saharan Africans, 19 Bini sub-Saharan Africans, 23 Kanuri West Africans, 50 Mayan Amerindians, 26 Quechuan Amerindians, 29 Nahua Amerindians.…”

Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines

“…Although the social and cultural influences of race on disease are undeniable, the role of genetics cannot be ignored. For example, an admixed individual with 20% EUR genetic ancestry may be at greater or lesser risk of certain diseases than an individual with 40% EUR genetic ancestry (56)(57)(58)(59)(60). In addition, the implications for pharmacogenomics exist as the nuances of drug effects or mechanisms may not be generalizable in the African American population due to high WA genetic variance (28,61).…”