ASPO Abstracts
Novel breast cancer susceptibility identified in African ancestry consortia under linkage peaks
Category: Cancer Health Disparities
Conference Year: 2021
Abstract Body:
Purpose. Continued expansion of genome-wide association studies into diverse populations is critical for an
improved understanding of both shared and unique contributors to breast cancer risk. Here, we performed a
genetic association study guided by a priori linkage findings from African ancestry pedigrees to identify novel and
potentially ancestry-specific associations. Methods. We performed a fixed effect inverse variance weighted meta-
analysis in four African ancestry breast cancer consortia and the Ghana Breast Health Study (a total of 9,241
breast cancer cases and 10,193 controls). We examined associations with overall breast cancer, as well as ER-
positive and ER-negative subtypes in three genomic regions that approximate a 1 LOD drop for significant linkage
peaks (3q26-27, 12q22-23, 16q21-22.1), including SNPs with MAF>0.001 and imputation quality score ≥0.6
(193,132 SNPs in total). We used region-wide significance thresholds determined a priori based on linkage
equilibrium information to identify the approximate number of independent SNPs (tests) in each region. Results.
On chr12q, we identified two significant associations for overall breast cancer which are 2.2 kb apart and in perfect
LD in YRI (rs1420647, A allele, OR=0.87, p=2.50x10-6; rs12322371, A allele, OR=0.88, p=3.15x10-6), and one
significant association for ER-negative breast cancer (rs770066000, T allele, OR=1.67, p=3.51x10-6). The two
chr12 SNPs associated with overall breast cancer are intron variants in CFAP54. On chr3, we identified two
significant associations with ER-negative breast cancer (rs184090918, A allele, OR=0.27, p=1.23x10-5;
rs76959804, A allele, OR=0.28, p=1.77x10-5) that are 2 kb apart and also in perfect LD in YRI. The significant
chr3 SNPs are upstream to open chromatin ENSR00000710716, which is actively regulated in mammary tissues.
The closest flanking genes are RPL7L1P8 upstream and LINC02031 downstream. On chr16, we identified one
association with ER-negative breast cancer (rs34147411, T allele, OR=1.62, p=8.82x10-6), an intron variant in
DUS2. Conclusion. Our study, guided by prior linkage evidence, identified novel associations with overall and ER-
negative breast cancer in an independent dataset comprised of women of African ancestry that warrant further
study.
Keywords: breast cancer African ancestry genetics