# Genetics of mammographic density and breast cancer risk in Latinas

> **NIH NIH K24** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $187,919

## Abstract

ABSTRACT
Mammographic density (MD) is a strong risk factor for breast cancer and family studies suggest it is highly
heritable. Genome wide association studies (GWAS) have identified a modest number of loci for MD, some of
which overlap with breast cancer risk. However, most of the heritability of breast cancer remains unexplained
and the underlying biology that explains the overlap between density and breast cancer risk remains poorly
understood.
This proposal will support Dr. Elad Ziv to continue scientific work on the genetics of mammographic density
and to continue to mentor clinician investigators in translational genetic studies of cancer. As part of the
current cycle of this K24, Dr. Ziv and his colleagues have investigated the genetics of breast cancer and MD in
Latina women. They have identified, via admixture mapping and GWAS, a very strong association for a single
nucleotide polymorphism (SNP) on chromosome 6q25. The minor allele at of this SNP is associated with
substantially reduced risk of breast cancer (Odds ratio of 0.6 for heterozygotes and 0.2 for homozygotes).
They also found that the minor allele is associated with a substantial reduction of mammographic density;
comparing women homozygous for the common allele vs. women homozygous for the low risk minor allele, the
median percent mammographic density is reduced from 16% to 8%, respectively. This SNP is found almost
exclusively in Latina women since this it originates in the Indigenous American populations from that region.
These results demonstrate the value of genetic studies in non-Caucasian populations for complex traits.
As part of the renewal for this project, they aim to extend these studies. They will focus on Latinas, a relatively
understudied population, where they have developed unique resources including a large GWAS and whole
exome sequencing data. First, they will investigate the possibility that rare variants at the 6q25 locus are
associated with MD in Latina women. They will perform targeted capture and sequencing of the region they
have previously found to be associated with breast cancer and density and they will perform rare variant
association tests. Second, they will use GWAS data from Latina women with breast cancer and controls to
determine what genes and pathways might be involved in the overlap between breast density and breast
cancer risk. Third, they will use data from their exome sequencing project (R01CA184545) to investigate
whether rare variants in coding regions in genes might underlie the shared heritability between MD and breast
cancer.
Dr. Ziv will also continue to mentor junior faculty, post-doctoral fellows, residents and students in research.
Mentees will work on the aims listed in this proposal and on several other large projects on genetic
susceptibility to breast cancer, genetics of mammographic density and genetics of multiple myeloma.

## Key facts

- **NIH application ID:** 9984974
- **Project number:** 5K24CA169004-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elad Ziv
- **Activity code:** K24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,919
- **Award type:** 5
- **Project period:** 2012-08-09 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984974

## Citation

> US National Institutes of Health, RePORTER application 9984974, Genetics of mammographic density and breast cancer risk in Latinas (5K24CA169004-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984974. Licensed CC0.

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