Validation of a genetic risk score for Arkansas women of color

Athena Davenport, Richard Allman, Gillian S. Dite, John L. Hopper, Erika Spaeth Tuff, Stewart Macleod, Susan Kadlubar, Michael Preston, Ronda Henry-Tillman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

African American women in the state of Arkansas have high breast cancer mortality rates. Breast cancer risk assessment tools developed for African American underestimate breast cancer risk. Combining African American breast cancer associated single-nucleotide polymorphisms (SNPs) into breast cancer risk algorithms may improve individualized estimates of a woman's risk of developing breast cancer and enable improved recommendation of screening and chemoprevention for women at high risk. The goal of this study was to confirm with an independent dataset consisting of Arkansas women of color, whether a genetic risk score derived from common breast cancer susceptibility SNPs can be combined with a clinical risk estimate provided by the Breast Cancer Risk Assessment Tool (BCRAT) to produce a more accurate individualized breast cancer risk estimate. A population-based cohort of African American women representative of Arkansas consisted of 319 cases and 559 controls for this study. Five-year and lifetime risks from the BCRAT were measured and combined with a risk score based on 75 independent susceptibility SNPs in African American women. We used the odds ratio (OR) per adjusted standard deviation to evaluate the improvement in risk estimates produced by combining the polygenic risk score (PRS) with 5-year and lifetime risk scores estimated using BCRAT. For 5-year risk OR per standard deviation increased from 1.84 to 2.08 with the addition of the polygenic risk score and from 1.79 to 2.07 for the lifetime risk score. Reclassification analysis indicated that 13% of cases had their 5-year risk increased above the 1.66% guideline threshold (NRI = 0.020 (95% CI -0.040, 0.080)) and 6.3% of cases had their lifetime risk increased above the 20% guideline threshold by the addition of the polygenic risk score (NRI = 0.034 (95% CI 0.000, 0.070)). Our data confirmed that discriminatory accuracy of BCRAT is improved for African American women in Arkansas with the inclusion of specific SNP breast cancer risk alleles.

Original languageEnglish (US)
Article numbere0204834
JournalPloS one
Volume13
Issue number10
DOIs
StatePublished - Jan 1 2018

Fingerprint

Color
breast neoplasms
color
Breast Neoplasms
African Americans
risk assessment
Risk assessment
single nucleotide polymorphism
risk estimate
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Odds Ratio
odds ratio
Guidelines
chemoprevention
taxonomic revisions
Chemoprevention
Case-Control Studies
Screening

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Davenport, A., Allman, R., Dite, G. S., Hopper, J. L., Tuff, E. S., Macleod, S., ... Henry-Tillman, R. (2018). Validation of a genetic risk score for Arkansas women of color. PloS one, 13(10), [e0204834]. https://doi.org/10.1371/journal.pone.0204834

Validation of a genetic risk score for Arkansas women of color. / Davenport, Athena; Allman, Richard; Dite, Gillian S.; Hopper, John L.; Tuff, Erika Spaeth; Macleod, Stewart; Kadlubar, Susan; Preston, Michael; Henry-Tillman, Ronda.

In: PloS one, Vol. 13, No. 10, e0204834, 01.01.2018.

Research output: Contribution to journalArticle

Davenport, A, Allman, R, Dite, GS, Hopper, JL, Tuff, ES, Macleod, S, Kadlubar, S, Preston, M & Henry-Tillman, R 2018, 'Validation of a genetic risk score for Arkansas women of color', PloS one, vol. 13, no. 10, e0204834. https://doi.org/10.1371/journal.pone.0204834
Davenport A, Allman R, Dite GS, Hopper JL, Tuff ES, Macleod S et al. Validation of a genetic risk score for Arkansas women of color. PloS one. 2018 Jan 1;13(10). e0204834. https://doi.org/10.1371/journal.pone.0204834
Davenport, Athena ; Allman, Richard ; Dite, Gillian S. ; Hopper, John L. ; Tuff, Erika Spaeth ; Macleod, Stewart ; Kadlubar, Susan ; Preston, Michael ; Henry-Tillman, Ronda. / Validation of a genetic risk score for Arkansas women of color. In: PloS one. 2018 ; Vol. 13, No. 10.
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