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. 2016 Jan 27;108(7):djv431.
doi: 10.1093/jnci/djv431. Print 2016 Jul.

Prostate Cancer Susceptibility in Men of African Ancestry at 8q24

Ying Han  1 , Kristin A Rand  1 , Dennis J Hazelett  1 , Sue A Ingles  1 , Rick A Kittles  1 , Sara S Strom  1 , Benjamin A Rybicki  1 , Barbara Nemesure  1 , William B Isaacs  1 , Janet L Stanford  1 , Wei Zheng  1 , Fredrick R Schumacher  1 , Sonja I Berndt  1 , Zhaoming Wang  1 , Jianfeng Xu  1 , Nadin Rohland  1 , David Reich  1 , Arti Tandon  1 , Bogdan Pasaniuc  1 , Alex Allen  1 , Dominique Quinque  1 , Swapan Mallick  1 , Dimple Notani  1 , Michael G Rosenfeld  1 , Ranveer Singh Jayani  1 , Suzanne Kolb  1 , Susan M Gapstur  1 , Victoria L Stevens  1 , Curtis A Pettaway  1 , Edward D Yeboah  1 , Yao Tettey  1 , Richard B Biritwum  1 , Andrew A Adjei  1 , Evelyn Tay  1 , Ann Truelove  1 , Shelley Niwa  1 , Anand P Chokkalingam  1 , Esther M John  1 , Adam B Murphy  1 , Lisa B Signorello  1 , John Carpten  1 , M Cristina Leske  1 , Suh-Yuh Wu  1 , Anslem J M Hennis  1 , Christine Neslund-Dudas  1 , Ann W Hsing  1 , Lisa Chu  1 , Phyllis J Goodman  1 , Eric A Klein  1 , S Lilly Zheng  1 , John S Witte  1 , Graham Casey  1 , Alex Lubwama  1 , Loreall C Pooler  1 , Xin Sheng  1 , Gerhard A Coetzee  1 , Michael B Cook  1 , Stephen J Chanock  1 , Daniel O Stram  1 , Stephen Watya  1 , William J Blot  1 , David V Conti  1 , Brian E Henderson  1 , Christopher A Haiman  1
Affiliations

Prostate Cancer Susceptibility in Men of African Ancestry at 8q24

Ying Han et al. J Natl Cancer Inst. .

Abstract

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

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Figures

Figure 1.
Figure 1.
Regional association plot of the 8q24 risk region in men of African ancestry. Single-nucleotide polymorphisms (SNPs) are plotted by position (x-axis) and -log10 P value (y-axis). The most associated SNP (purple diamond) is rs114798100, and the surrounding SNPs are colored to indicate pairwise correlation in African ancestry populations (AFR panel in 1000 Genomes). Below shows the overlap of the three most associated variants in ‘region 2’ as well as variants correlated at r2 ≥ 0.7 with rs114798100 (green), rs72725879 (red) and rs111906932 (blue) (Supplementary Table 7, available online) and functional annotations from DNAseI, histone modification, and ChIP-seq experiments in LNCaP (Supplementary Table 8 and Supplementary Methods, available online). All statistical tests were two-sided.
See this image and copyright information in PMC

References

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