Multiple newly identified loci associated with prostate cancer susceptibility

  title={Multiple newly identified loci associated with prostate cancer susceptibility},
  author={Rosalind A. Eeles and Zsofia Kote-Jarai and Graham G. Giles and Ali Amin Al Olama and Michelle Guy and Sarah K Jugurnauth and Shani A. Mulholland and Daniel A. Leongamornlert and Stephen M. Edwards and Jonathan Morrison and Helen I. Field and Melissa C. Southey and Gianluca Severi and Jenny L. Donovan and Freddie C. Hamdy and David P. Dearnaley and Kenneth Ross Muir and Charmaine D. Smith and Melisa Bagnato and Audrey Ardern-jones and Amanda L. Hall and Lynne T. O'Brien and Beatrice N Gehr-Swain and Rosemary A. Wilkinson and Angela Cox and Sarah J. Lewis and Paul M. Brown and Sameer Jhavar and Malgorzata Tymrakiewicz and Artitaya Lophatananon and Sarah L Bryant and Alan Horwich and Robert A. Huddart and Vincent Khoo and Chris C. Parker and Christopher J Woodhouse and Alan Thompson and Timothy J. Christmas and Chris Ogden and Cyril Fisher and Charles Jamieson and Colin S Cooper and Dallas R. English and John L. Hopper and David E. Neal and Douglas F. Easton},
  journal={Nature Genetics},
Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at ≤60 years or with a family history of disease, and 1,894 population-screened controls with… 

Genome-wide association study identifies new prostate cancer susceptibility loci.

A new susceptibility locus associated with overall PrCa risk at 2q37.3 is identified and a locus suggested by an earlier GWAS at 12q13 is confirmed, although it is unclear whether these or other loci are differentially associated with PrCa subtypes.

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

The results of stage 3 are reported, in which 1,536 SNPs are evaluated in 4,574 individuals with prostate cancer (cases) and 4,164 controls and a SNP in TERT more strongly associated with PrCa than that previously reported is identified.

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

The study is extended to evaluate promising associations in a second stage in which 43,671 SNPs are genotyped in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies.

Novel genetic loci associated with prostate cancer in the Japanese population.

This study identified five new loci associated with prostate cancer, which suggests that there are complex and diverse etiological processes leading to prostate cancer among different ethnic backgrounds, and suggests that the power of GWAS can be enhanced by examining different ethnic populations to uncover gene variants that are responsible for causing human diseases.

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled.

Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population

Five new loci for prostate cancer susceptibility are reported here, at 5p15 (λ-corrected probability PGC = 3.9 × 10−18), GPRC6A/RFX6 (PGC = 1.6 ×10−12), 13q22 ( PGC = 2.8 × 10–10−9), C2orf43 (PGD = 7.5 × 10.–8) and FOXP4 (PGE = 7−8).

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Two Susceptibility Loci Identified for Prostate Cancer Aggressiveness

A multistage, case-only genome-wide association study of prostate cancer cases identifies two loci associated with Gleason score, a pathological measure of disease aggressiveness, and the proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.

Identification of an aggressive prostate cancer predisposing variant at 11q13

The results indicate that the intronic variant IVS6‐43A>G increases the familial and unselected prostate cancer risk in a Finnish population and contributes to the aggressive progression of the disease in a high‐penetrance manner.



Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Observations indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry, and it is estimated that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked byrs1447295.

Genome-wide association study identifies novel breast cancer susceptibility loci

To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.

A common variant associated with prostate cancer in European and African populations

Allele −8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US, and the association was replicated in an African American case- control group with a similar OR, leading to a greater estimated PAR.

Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

Results from eight case-control groups demonstrate that this variant in TCF2 (HNF1β), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5, confers protection against type 2 diabetes.

Multiple regions within 8q24 independently affect risk for prostate cancer

Seven prostate cancer risk variants are identified, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 × 10−19 for the strongest association), and common genotypes that span a more than fivefold range of susceptibility to cancer in some populations are defined.

ELAC2/HPC2 polymorphisms, prostate-specific antigen levels, and prostate cancer.

There is no evidence that either ELAC2 polymorphism is associated with prostate cancer or PSA levels, according to a population-based study in Australia.

Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

Admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it and finding that the previously described alleles do not explain more than a fraction of the admixture signal.

Unravelling the genetics of prostate cancer

  • S. EdwardsR. Eeles
  • Biology
    American journal of medical genetics. Part C, Seminars in medical genetics
  • 2004
The evidence for the existence, first of familial prostate cancer, and second, for the presence of such a high‐risk gene in those families by epidemiological and experimental approaches are investigated.

Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene.

It is confirmed that BRCA2 is a high-risk prostate-cancer-susceptibility gene and have potential implications for the management of early-onset prostate cancer, in both patients and their relatives.

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.