Evidence map›Paper›PMID 37658461›Full record

ArticleGenome medicine2023

Interplay of Mendelian and polygenic risk factors in Arab breast cancer patients.

Mohammed Al-Jumaan, Hoyin Chu, Abdullah Alsulaiman, Sabrina Y Camp, Seunghun Han, Riaz Gillani, Yousef Al Marzooq, Fatmah Almulhim, Chittibabu Vatte, Areej Al Nemer and 4 more

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Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Mohammed Al-Jumaan *College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Hoyin Chu *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Abdullah AlsulaimanCollege of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Sabrina Y CampDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Seunghun HanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Riaz GillaniCancer Program, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yousef Al MarzooqCollege of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Fatmah AlmulhimCollege of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Chittibabu VatteCollege of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Areej Al NemerCollege of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Afnan AlmuhannaCollege of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Amein Al-Ali *College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Saud H AlDubayan *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. saud_aldubayan@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-9062-3399

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBreast cancer patients from the indigenous Arab population present much earlier than patients from Western countries and have traditionally been underrepresented in cancer genomics studies. The contribution of polygenic and Mendelian risk toward the earlier onset of breast cancer in the population remains elusive.

methodsWe performed low-pass whole genome sequencing (lpWGS) and whole-exome sequencing (WES) from 220 female breast cancer patients unselected for positive family history from the indigenous Arab population. Using publicly available resources, we imputed population-specific variants and calculated breast cancer burden-sensitive polygenic risk scores (PRS). Variant pathogenicity was also evaluated on exome variants with high coverage.

resultsVariants imputed from lpWGS showed high concordance with paired exome (median dosage correlation: 0.9459, Interquartile range: 0.9410-0.9490). After adjusting the PRS to the Arab population, we found significant associations between PRS performance in risk prediction and first-degree relative breast cancer history prediction (Spearman rho=0.43, p = 0.03), where breast cancer patients in the top PRS decile are 5.53 (95% CI 1.76-17.97, p = 0.003) times more likely also to have a first-degree relative diagnosed with breast cancer compared to those in the middle deciles. In addition, we found evidence for the genetic liability threshold model of breast cancer where among patients with a family history of breast cancer, pathogenic rare variant carriers had significantly lower PRS than non-carriers (p = 0.0205, Mann-Whitney U test) while for non-carriers every standard deviation increase in PRS corresponded to 4.52 years (95% CI 8.88-0.17, p = 0.042) earlier age of presentation.

conclusionsOverall, our study provides a framework to assess polygenic risk in an understudied population using lpWGS and identifies common variant risk as a factor independent of pathogenic variant carrier status for earlier age of onset of breast cancer among indigenous Arab breast cancer patients.

Indexed as

Breast NeoplasmsArabsBreastExomeFemaleHumansRisk FactorsAge of onsetArab populationBreast cancerImputationLow-pass whole genome sequencingPathogenic variantsPolygenic risk score

Identifiers

PMID37658461
PMCPMC10474689

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.