Generalizability of established prostate cancer risk variants in men of African ancestry

Ying Han; Lisa B. Signorello; Sara S. Strom; Rick A. Kittles; Benjamin A. Rybicki; Janet L. Stanford; Phyllis J. Goodman; Sonja I. Berndt; John Carpten; Graham Casey; Lisa Chu; David V. Conti; Kristin A. Rand; W. Ryan Diver; Anselm J.M. Hennis; Esther M. John; Adam S. Kibel; Eric A. Klein; Suzanne Kolb; Loic Le Marchand; M. Cristina Leske; Adam B. Murphy; Christine Neslund-Dudas; Jong Y. Park; Curtis Pettaway; Timothy R. Rebbeck; Susan M. Gapstur; S. Lilly Zheng; Suh Yuh Wu; John S. Witte; Jianfeng Xu; William Isaacs; Sue A. Ingles; Ann Hsing; Douglas F. Easton; Rosalind A. Eeles; Fredrick R. Schumacher; Stephen Chanock; Barbara Nemesure; William J. Blot; Daniel O. Stram; Brian E. Henderson; Christopher A. Haiman

doi:10.1002/ijc.29066

Generalizability of established prostate cancer risk variants in men of African ancestry

Ying Han
, Lisa B. Signorello
, Sara S. Strom
, Rick A. Kittles
, Benjamin A. Rybicki
, Janet L. Stanford
, Phyllis J. Goodman
, Sonja I. Berndt
, John Carpten
, Graham Casey
, Lisa Chu
, David V. Conti
, Kristin A. Rand
, W. Ryan Diver
, Anselm J.M. Hennis
, Esther M. John
, Adam S. Kibel
, Eric A. Klein
, Suzanne Kolb
, Loic Le Marchand

M. Cristina Leske, Adam B. Murphy, Christine Neslund-Dudas, Jong Y. Park, Curtis Pettaway, Timothy R. Rebbeck, Susan M. Gapstur, S. Lilly Zheng, Suh Yuh Wu, John S. Witte, Jianfeng Xu, William Isaacs, Sue A. Ingles, Ann Hsing, Douglas F. Easton, Rosalind A. Eeles, Fredrick R. Schumacher, Stephen Chanock, Barbara Nemesure, William J. Blot, Daniel O. Stram, Brian E. Henderson, Christopher A. Haiman

Family , Population and Preventative Medicine

University of Southern California
Harvard University
Ludwig Center at Dana-Farber/Harvard Cancer Center
University of Texas Health Science Center at Houston
University of Illinois at Chicago
Henry Ford Health System
Fred Hutchinson Cancer Research Center
SWOG Statistical Center
National Institutes of Health
Translational Genomics Research Institute
Cancer Prevention Institute of California
American Cancer Society
Stony Brook University
The University of the West Indies
Ministry of Health Barbados
Stanford University
Brigham and Women’s Hospital
Cleveland Clinic Foundation
Connecticut Agricultural Experiment Station
Northwestern University
Moffitt Cancer Center
University of Texas MD Anderson Cancer Center
University of Pennsylvania
Wake Forest University
University of California at San Francisco
Johns Hopkins University
University of Cambridge
The Institute of Cancer Research
Royal Marsden NHS Foundation Trust
Vanderbilt University
International Epidemiology Institute

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p=3.7 × 10^-26) and rs6983561 (p=1.1 × 10^-16) at 8q24, as well as rs7210100 (p=5.4 × 10^-8) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR)=1.12, p=7.3 × 10^-98]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

Original language	English
Pages (from-to)	1210-1217
Number of pages	8
Journal	International Journal of Cancer
Volume	136
Issue number	5
DOIs	https://doi.org/10.1002/ijc.29066
State	Published - Mar 1 2015

Keywords

African ancestry
Generalizability
Genetic risk variant
Prostate cancer

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10.1002/ijc.29066

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Han, Y., Signorello, L. B., Strom, S. S., Kittles, R. A., Rybicki, B. A., Stanford, J. L., Goodman, P. J., Berndt, S. I., Carpten, J., Casey, G., Chu, L., Conti, D. V., Rand, K. A., Diver, W. R., Hennis, A. J. M., John, E. M., Kibel, A. S., Klein, E. A., Kolb, S., ... Haiman, C. A. (2015). Generalizability of established prostate cancer risk variants in men of African ancestry. International Journal of Cancer, 136(5), 1210-1217. https://doi.org/10.1002/ijc.29066

@article{241fb44963194bed93608d8497edc7c7,

title = "Generalizability of established prostate cancer risk variants in men of African ancestry",

abstract = "Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83\%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37\%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p=3.7 × 10-26) and rs6983561 (p=1.1 × 10-16) at 8q24, as well as rs7210100 (p=5.4 × 10-8) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37\%) to 44 (54\%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR)=1.12, p=7.3 × 10-98]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.",

keywords = "African ancestry, Generalizability, Genetic risk variant, Prostate cancer",

author = "Ying Han and Signorello, \{Lisa B.\} and Strom, \{Sara S.\} and Kittles, \{Rick A.\} and Rybicki, \{Benjamin A.\} and Stanford, \{Janet L.\} and Goodman, \{Phyllis J.\} and Berndt, \{Sonja I.\} and John Carpten and Graham Casey and Lisa Chu and Conti, \{David V.\} and Rand, \{Kristin A.\} and Diver, \{W. Ryan\} and Hennis, \{Anselm J.M.\} and John, \{Esther M.\} and Kibel, \{Adam S.\} and Klein, \{Eric A.\} and Suzanne Kolb and \{Le Marchand\}, Loic and Leske, \{M. Cristina\} and Murphy, \{Adam B.\} and Christine Neslund-Dudas and Park, \{Jong Y.\} and Curtis Pettaway and Rebbeck, \{Timothy R.\} and Gapstur, \{Susan M.\} and Zheng, \{S. Lilly\} and Wu, \{Suh Yuh\} and Witte, \{John S.\} and Jianfeng Xu and William Isaacs and Ingles, \{Sue A.\} and Ann Hsing and Easton, \{Douglas F.\} and Eeles, \{Rosalind A.\} and Schumacher, \{Fredrick R.\} and Stephen Chanock and Barbara Nemesure and Blot, \{William J.\} and Stram, \{Daniel O.\} and Henderson, \{Brian E.\} and Haiman, \{Christopher A.\}",

note = "Publisher Copyright: {\textcopyright} 2014 UICC.",

year = "2015",

month = mar,

day = "1",

doi = "10.1002/ijc.29066",

language = "English",

volume = "136",

pages = "1210--1217",

journal = "International Journal of Cancer",

issn = "0020-7136",

number = "5",

}

Han, Y, Signorello, LB, Strom, SS, Kittles, RA, Rybicki, BA, Stanford, JL, Goodman, PJ, Berndt, SI, Carpten, J, Casey, G, Chu, L, Conti, DV, Rand, KA, Diver, WR, Hennis, AJM, John, EM, Kibel, AS, Klein, EA, Kolb, S, Le Marchand, L, Leske, MC, Murphy, AB, Neslund-Dudas, C, Park, JY, Pettaway, C, Rebbeck, TR, Gapstur, SM, Zheng, SL, Wu, SY, Witte, JS, Xu, J, Isaacs, W, Ingles, SA, Hsing, A, Easton, DF, Eeles, RA, Schumacher, FR, Chanock, S, Nemesure, B, Blot, WJ, Stram, DO, Henderson, BE & Haiman, CA 2015, 'Generalizability of established prostate cancer risk variants in men of African ancestry', International Journal of Cancer, vol. 136, no. 5, pp. 1210-1217. https://doi.org/10.1002/ijc.29066

TY - JOUR

T1 - Generalizability of established prostate cancer risk variants in men of African ancestry

AU - Han, Ying

AU - Signorello, Lisa B.

AU - Strom, Sara S.

AU - Kittles, Rick A.

AU - Rybicki, Benjamin A.

AU - Stanford, Janet L.

AU - Goodman, Phyllis J.

AU - Berndt, Sonja I.

AU - Carpten, John

AU - Casey, Graham

AU - Chu, Lisa

AU - Conti, David V.

AU - Rand, Kristin A.

AU - Diver, W. Ryan

AU - Hennis, Anselm J.M.

AU - John, Esther M.

AU - Kibel, Adam S.

AU - Klein, Eric A.

AU - Kolb, Suzanne

AU - Le Marchand, Loic

AU - Leske, M. Cristina

AU - Murphy, Adam B.

AU - Neslund-Dudas, Christine

AU - Park, Jong Y.

AU - Pettaway, Curtis

AU - Rebbeck, Timothy R.

AU - Gapstur, Susan M.

AU - Zheng, S. Lilly

AU - Wu, Suh Yuh

AU - Witte, John S.

AU - Xu, Jianfeng

AU - Isaacs, William

AU - Ingles, Sue A.

AU - Hsing, Ann

AU - Easton, Douglas F.

AU - Eeles, Rosalind A.

AU - Schumacher, Fredrick R.

AU - Chanock, Stephen

AU - Nemesure, Barbara

AU - Blot, William J.

AU - Stram, Daniel O.

AU - Henderson, Brian E.

AU - Haiman, Christopher A.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p=3.7 × 10-26) and rs6983561 (p=1.1 × 10-16) at 8q24, as well as rs7210100 (p=5.4 × 10-8) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR)=1.12, p=7.3 × 10-98]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

AB - Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p=3.7 × 10-26) and rs6983561 (p=1.1 × 10-16) at 8q24, as well as rs7210100 (p=5.4 × 10-8) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR)=1.12, p=7.3 × 10-98]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

KW - African ancestry

KW - Generalizability

KW - Genetic risk variant

KW - Prostate cancer

UR - https://www.scopus.com/pages/publications/84918776670

U2 - 10.1002/ijc.29066

DO - 10.1002/ijc.29066

M3 - Article

C2 - 25044450

AN - SCOPUS:84918776670

SN - 0020-7136

VL - 136

SP - 1210

EP - 1217

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 5

ER -

Generalizability of established prostate cancer risk variants in men of African ancestry

Abstract

Keywords

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