Kathleen Cooney

Overview:

Dr. Cooney is Chair of the Duke Department of Medicine and Interim Director of the Duke Center for Applied Genomics and Precision Medicine.

She is a medical oncologist focused in caring for men with prostate cancer, and is internationally known for her investigations focused on the genetic epidemiology of prostate cancer.

Her research led to the important discovery of a recurrent mutation in the HOXB13 gene that increases the chances of being diagnosed with prostate cancer and is estimated to account for 5 percent of hereditary prostate cancer cases worldwide. Since men with HOXB13 mutations are at an increased risk of prostate cancer, they may benefit from participation in screening and potentially prevention protocols in the future.

Dr. Cooney’s research continues with federal funding to identify germline mutations associated with lethal and aggressive prostate cancer as well as prostate cancer in African American men.

Positions:

George Barth Geller Distinguished Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Chair, Department of Medicine

Medicine
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Member of Duke Molecular Physiology Institute

Duke Molecular Physiology Institute
School of Medicine

Education:

M.D. 1984

University of Pennsylvania, School of Medicine

Intern/Resident, Internal Medicine

University of Michigan, Ann Arbor

Chief Medical Resident, Internal Medicine

University of Michigan, Ann Arbor

Fellow, Hematology / Oncology

University of Michigan, Ann Arbor

Grants:

The Contribution of Rare Variants in Familial Clustering of Prostate and Breast Cancer in African Americans

Administered By
Medicine, Medical Oncology
Awarded By
Wayne State University
Role
Principal Investigator
Start Date
End Date

The Role of Mutations in BRCA2 and Other Known and Novel Cancer Susceptibility Genes in Inherited Risk for Lethal Prostate Cancer - IMPACT

Administered By
Medicine, Medical Oncology
Awarded By
Johns Hopkins University
Role
Principal Investigator
Start Date
End Date

Characterizing the Genetic Landscape of Prostate Cancer in Young African American Men - HDRA

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Publications:

The HOXB13 variant X285K is associated with clinical significance and early age at diagnosis in African American prostate cancer patients.

BACKGROUND: Recently, a novel HOXB13 variant (X285K) was observed in men of African descent with prostate cancer (PCa) in Martinique. Little is known about this or other variants in HOXB13 which may play a role in PCa susceptibility in African-American (AA) men. METHODS: We sequenced HOXB13 in an AA population of 1048 men undergoing surgical treatment for PCa at Johns Hopkins Hospital. RESULTS: Seven non-synonymous germline variants were observed in the patient population. While six of these variants were seen only once, X285K was found in eight patients. In a case-case analysis, we find that carriers of this latter variant are at increased risk of clinically significant PCa (1.2% carrier rate in Gleason Score ≥7 PCa vs. 0% in Gleason Score <7 PCa, odds ratio, OR = inf; 95% Confidence Interval, 95%CI:1.05-inf, P = 0.028), as well as PCa with early age at diagnosis (2.4% carrier rate in patients <50 year vs. 0.5% carrier rate in patients ≥50 year, OR = 5.25, 95% CI:1.00-28.52, P = 0.03). CONCLUSIONS: While this variant is rare in the AA population (~0.2% MAF), its ancestry-specific occurrence and apparent preferential association with risk for the more aggressive disease at an early age emphasizes its translational potential as an important, novel PCa susceptibility marker in the high-risk AA population.
Authors
Na, R; Wei, J; Sample, CJ; Gielzak, M; Choi, S; Cooney, KA; Rabizadeh, D; Walsh, PC; Zheng, LS; Xu, J; Isaacs, WB
MLA Citation
Na, Rong, et al. “The HOXB13 variant X285K is associated with clinical significance and early age at diagnosis in African American prostate cancer patients.Br J Cancer, vol. 126, no. 5, Mar. 2022, pp. 791–96. Pubmed, doi:10.1038/s41416-021-01622-4.
URI
https://scholars.duke.edu/individual/pub1503240
PMID
34799695
Source
pubmed
Published In
Br J Cancer
Volume
126
Published Date
Start Page
791
End Page
796
DOI
10.1038/s41416-021-01622-4

KLK3 germline mutation I179T complements DNA repair genes for predicting prostate cancer progression.

BACKGROUND: Germline mutations in DNA repair genes and KLK3 have been associated with adverse prostate cancer (PCa) outcomes in separate studies but never jointly. The objective of this study is to simultaneously assess these two types of germline mutations. METHODS: Germline rare pathogenic mutations (RPMs) in 9 commonly tested DNA repair genes and KLK3 variants were tested for their associations with PCa progression in two PCa cohorts: (1) hospital-based PCa patients treated with radical surgery at the Johns Hopkins Hospital (JHH, N = 1943), and (2) population-based PCa patients in the UK Biobank (UKB, N = 10,224). Progression was defined as metastasis and/or PCa-specific death (JHH) and PCa-specific death (UKB). RPMs of DNA repair genes were annotated using the American College of Medical Genetics recommendations. Known KLK3 variants were genotyped. Associations were tested using a logistic regression model adjusting for genetic background (top ten principal components). RESULTS: In the JHH, 3.2% (59/1,843) of patients had RPMs in 9 DNA repair genes; odds ratio (OR, 95% confidence interval) for progression was 2.99 (1.6-5.34), P < 0.001. In comparison, KLK3 I179T mutation was more common; 9.7% (189/1,943) carried the mutation, OR = 1.6 (1.05-2.37), P = 0.02. Similar results were found in the UKB. Both types of mutations remained statistically significant in multivariable analyses. In the combined cohort, compared to patients without any mutations (RPMs-/KLK3-), RPMs-/KLK3+ patients had modestly increased risk for progression [OR = 1.54 (1.15-2.02), P = 0.003], and RPMs+/KLK3+ patients had greatly increased risk for progression [OR = 5.41 (2.04-12.99), P < 0.001]. Importantly, associations of mutations with PCa progression were found in patients with clinically defined low- or intermediate risk for disease progression. CONCLUSIONS: Two different cohorts consistently demonstrate that KLK3 I179T and RPMs of nine commonly tested DNA repair genes are complementary for predicting PCa progression. These results are highly relevant to PCa germline testing and provide critical information for KLK3 I179T to be considered in guidelines.
Authors
Xu, J; Shi, Z; Wei, J; Na, R; Resurreccion, WK; Wang, C-H; Sample, C; Han, M; Zheng, SL; Cooney, KA; Helfand, BT; Isaacs, WB
MLA Citation
Xu, Jianfeng, et al. “KLK3 germline mutation I179T complements DNA repair genes for predicting prostate cancer progression.Prostate Cancer Prostatic Dis, Feb. 2022. Pubmed, doi:10.1038/s41391-021-00466-6.
URI
https://scholars.duke.edu/individual/pub1509914
PMID
35149774
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-021-00466-6

Observed evidence for guideline-recommended genes in predicting prostate cancer risk from a large population-based cohort.

BACKGROUND: Germline testing for prostate cancer (PCa) is now recommended by the National Comprehensive Cancer Network. While multi-gene testing has been proposed, evidence for their association with PCa risk is not well established. METHODS: We tested associations of pathogenic/likely pathogenic mutations in 10 guideline-recommended genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, MLH1, MSH2, MSH6, PMS2, and HOXB13) with PCa risk in the UK Biobank, a population-based cohort. Mutations were annotated based on prostate-specific transcripts using the American College of Medical Genetics and Genomics standards. Associations were tested in 4399 PCa cases and 85,403 unaffected male controls using logistic regression adjusting for age and genetic background. p < .005 was considered significant based on Bonferroni correction. RESULTS: Among the 10 tested genes, significantly higher mutation carrier rates in PCa cases versus controls were found for four genes at p < .005; HOXB13, BRCA2, ATM, and CHEK2, with odds ratios (95% confidence interval) estimated at 4.96 (3.62-6.69), 3.23 (2.23-4.56), 2.95 (2.01-4.22), 1.94 (1.43-2.58), respectively. No significant association was found between mutation carrier status and age at PCa diagnosis or family history of PCa. Despite the large sample size of this study, statistical power remains limited, especially for genes where pathogenic mutation carrier rates are extremely rare (<0.03%). CONCLUSION: Observed evidence for PCa risk was found for four of the 10 guideline-recommended genes in this large population-based study. Mutations in these four genes can be interpreted with confidence in genetic counseling for PCa risk assessment. Evidence for the remaining six genes needs to be further evaluated in larger studies.
Authors
Wei, J; Yang, W; Shi, Z; Lu, L; Wang, Q; Resurreccion, WK; Engelmann, V; Zheng, SL; Hulick, PJ; Cooney, KA; Isaacs, WB; Helfand, BT; Lu, J; Xu, J
MLA Citation
Wei, Jun, et al. “Observed evidence for guideline-recommended genes in predicting prostate cancer risk from a large population-based cohort.Prostate, vol. 81, no. 13, Sept. 2021, pp. 1002–08. Pubmed, doi:10.1002/pros.24195.
URI
https://scholars.duke.edu/individual/pub1488640
PMID
34254341
Source
pubmed
Published In
Prostate
Volume
81
Published Date
Start Page
1002
End Page
1008
DOI
10.1002/pros.24195

Prostate Cancer Predisposition.

The identification and characterization of alterations in prostate cancer (PCa)-predisposing genes can help to inform screening strategies in undiagnosed men and treatment options in men in both the clinically localized and in the metastatic setting. This review provides an overview of the genetic basis underlying hereditary predisposition to PCa, the current role of genetics and PCa risk assessment, and how genetic risk factors affect aggressiveness and lethality of PCa.
Authors
Bhanji, Y; Isaacs, WB; Xu, J; Cooney, KA
MLA Citation
Bhanji, Yasin, et al. “Prostate Cancer Predisposition.Urol Clin North Am, vol. 48, no. 3, Aug. 2021, pp. 283–96. Pubmed, doi:10.1016/j.ucl.2021.03.001.
URI
https://scholars.duke.edu/individual/pub1485988
PMID
34210485
Source
pubmed
Published In
Urol Clin North Am
Volume
48
Published Date
Start Page
283
End Page
296
DOI
10.1016/j.ucl.2021.03.001

"Sheroes": Celebrating Women in Medicine Month During the Time of COVID-19.

Authors
Sata, SS; Vekstein, B; Svetkey, L; Criscione-Schreiber, L; Cooney, KA
MLA Citation
Sata, Suchita Shah, et al. “"Sheroes": Celebrating Women in Medicine Month During the Time of COVID-19.Acad Med, vol. 96, no. 5, May 2021, pp. e17–18. Pubmed, doi:10.1097/ACM.0000000000003967.
URI
https://scholars.duke.edu/individual/pub1481290
PMID
33538481
Source
pubmed
Published In
Acad Med
Volume
96
Published Date
Start Page
e17
End Page
e18
DOI
10.1097/ACM.0000000000003967