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 MarchandM. 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

School of Medicine

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

47 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 (US)
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

ASJC Scopus subject areas

Oncology
Cancer Research

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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

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

@article{2ac593ad8b2942479ed563d925d9e5f7,

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 (US)",

volume = "136",

pages = "1210--1217",

journal = "International Journal of Cancer",

issn = "0020-7136",

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number = "5",

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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

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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

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Keywords

ASJC Scopus subject areas

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