Abstract 3517: A germline variant at 8q24 contributes to familial clustering of prostate cancer in men of African ancestry

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.3517-3517
• Main Authors: Darst, Burcu F., Bensen, Jeannette T., Ingles, Sue A., Rybicki, Benjamin A., Nemesure, Barbara, John, Esther M., Fowke, Jay H., Stevens, Victoria L., Berndt, Sonja I., Huff, Chad D., Park, Jong Y., Zheng, Wei, Ostrander, Elaine A., Srivastava, Shiv, Carpten, John, Sellers, Thomas A., Sanderson, Maureen, Crawford, Dana C., Cussenot, Olivier, Cullen, Jennifer, Kittles, Rick A., Xu, Jianfeng, Kote-Jarai, Zsofia, Multigner, Luc, Parent, Marie-Elise, Menegaux, Florence, Cancel-Tassin, Geraldine, Kibel, Adam S., Klein, Eric A., Goodman, Phyllis J., Hu, Jennifer J., Casey, Graham, Hennis, Anselm J., Thompson, Ian M., Leach, Robin, Mohler, James L., Fontham, Elizabeth T., Smith, Gary J., Taylor, Jack A., Eeles, Rosalind A., Brureau, Laurent, Chanock, Stephen J., Watya, Stephen, Stanford, Janet L., Mandal, Diptasri, Isaacs, William B., Cooney, Kathleen A., Blot, William J., Conti, David V., Haiman, Christopher A.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2020-3517

Germline variation at 8q24 is the strongest risk factor for prostate cancer (PCa) across all racial and ethnic populations. While most 8q24 associations have been observed across populations, rs72725854 [T risk allele frequency ~6%] is only found in men of African ancestry and is the strongest known genome-wide association signal for PCa in this population. We investigated whether the T allele of rs72725854 is associated with PCa family history and age at diagnosis, characteristics known to have a strong genetic component. Analyses were performed using a sample of 9,052 cases and 8,595 controls from the African Ancestry Prostate Cancer (AAPC) GWAS Consortium and the ELLIPSE/PRACTICAL OncoArray Consortium. Participants were unselected for PCa family history. Among cases, 23.7% carried at least one copy of the T allele versus 11.6% of controls. The OR was 2.29 (95% CI=2.10–2.49) for TA heterozygotes and 5.04 (95% CI=3.36–7.55) for TT homozygotes. The percentage of cases carrying the T allele was significantly greater for men with a PCa family history (27.4% vs. 22.7% without a family history, p=0.002) and for men diagnosed 100 ng/ml or death from PCa), 25.4% for high-risk disease (stage T3/T4, Gleason 8-10, or PSA=20-100 ng/ml), 24.6% for intermediate-risk disease (Gleason=7, stage T1/T2, and PSA=10-20 ng/ml), and 21.4% for low-risk disease (Gleason