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Meta-Analysis
. 2017 Aug 1;109(8):djx084.
doi: 10.1093/jnci/djx084.

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

David V Conti  1 Kan Wang  1 Xin Sheng  1 Jeannette T Bensen  2   3 Dennis J Hazelett  4 Michael B Cook  5 Sue A Ingles  1   6 Rick A Kittles  7 Sara S Strom  8 Benjamin A Rybicki  9 Barbara Nemesure  10 William B Isaacs  11 Janet L Stanford  12   13 Wei Zheng  14 Maureen Sanderson  15 Esther M John  16   17 Jong Y Park  18 Jianfeng Xu  19 Victoria L Stevens  20 Sonja I Berndt  5 Chad D Huff  8 Zhaoming Wang  21 Edward D Yeboah  22   23 Yao Tettey  22   23 Richard B Biritwum  22   23 Andrew A Adjei  22   23 Evelyn Tay  22   23 Ann Truelove  24 Shelley Niwa  24 Thomas A Sellers  18 Kosj Yamoah  25 Adam B Murphy  26 Dana C Crawford  27 Susan M Gapstur  20 William S Bush  27 Melinda C Aldrich  28 Olivier Cussenot  29 Gyorgy Petrovics  30 Jennifer Cullen  30 Christine Neslund-Dudas  9 Mariana C Stern  1   6 Zsofia-Kote Jarai  31 Koveela Govindasami  32 Anand P Chokkalingam  33 Ann W Hsing  34 Phyllis J Goodman  35 Thomas Hoffmann  36 Bettina F Drake  37 Jennifer J Hu  38 Peter E Clark  39 Stephen K Van Den Eeden  40 Pascal Blanchet  41   42   43 Jay H Fowke  44 Graham Casey  45 Anselm J M Hennis  10   46 Ying Han  1 Alexander Lubwama  47 Ian M Thompson Jr  48 Robin Leach  48 Douglas F Easton  49 Fredrick Schumacher  50 David J Van den Berg  1 Susan M Gundell  1 Alex Stram  1 Peggy Wan  1 Lucy Xia  1 Loreall C Pooler  1 James L Mohler  3   51 Elizabeth T H Fontham  52 Gary J Smith  51 Jack A Taylor  53 Shiv Srivastava  30 Rosalind A Eeles  31   54 John Carpten  55 Adam S Kibel  56   57 Luc Multigner  58 Marie-Elise Parent  59 Florence Menegaux  60 Geraldine Cancel-Tassin  29 Eric A Klein  61 Laurent Brureau  41   42   43 Daniel O Stram  1   6 Stephen Watya  47   62 Stephen J Chanock  5 John S Witte  36   63 William J Blot  14 Brian E Henderson  1   6 Christopher A Haiman  1   6 PRACTICAL/ELLIPSE Consortium
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Free PMC article
Meta-Analysis

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

David V Conti et al. J Natl Cancer Inst. .
Free PMC article

Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Figures

Figure 1.
Figure 1.
Regional plot of a novel genome-wide statistically significant prostate cancer risk region at chromosome 13q34. Single nucleotide polymorphisms (SNPs) are plotted by their position 110 kb on either side of the index SNP (purple diamond) on the chromosome against their association (−log10P) with prostate cancer risk in men of African ancestry. SNPs surrounding the index SNP are colored to indicate the local linkage disequilibrium (LD) structure using pairwise r2 data from the African ancestry samples panel of the 1000 Genomes Project (November 2014 phase III). Below are peaks from transcription factor (TF) and histone modification ChIP-seq experiments in the same genomic window (see the Supplementary Methods, available online). All ChIP-seq in LNCaP unless otherwise indicated. AR = androgen receptor; CTCF = CCCTC-binding factor; LNCaP = Lymph Node Carcinoma of the Prostate cell line.

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