Search

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Multiple myeloma is a cancer of the plasma cells, and the complete aetiology of the disease is still unclear. Here the authors perform an additional GWAS analysis followed by a meta-analysis with existing GWAS and replication genotyping and identify 6 novel risk loci and utilise gene expression, epigenetic profiling and in situ Hi-C data to further our understanding of MM susceptibility.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

While GWAS have uncovered susceptibility loci for B-cell precursor acute lymphoblastic leukemia (BCP-ALL), much of the heritable risk remains undiscovered. Here, the authors perform a meta-analysis of two existing BCP-ALL GWAS together with an unpublished GWAS to identify risk loci at 8q24.21 and 2q22.3.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

A polygenic hazard score (PHS₁) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS₂) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

The identification of individuals carrying cancer susceptibility genetic variants could be improved by peridiagnostic cancer genetic testing and cascade testing of the relatives of patients diagnosed with cancer. Herein we discuss two studies that highlight the importance of active involvement of the medical team, both in informing the relatives and offering pre-test telephone genetic counselling.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

Classical Hodgkin lymphoma is a cancer that originates in lymph nodes. Little is known about its genetic susceptibility. Here, the authors combined existing and new genome-wide association studies to identify risk loci for classical Hodgkin lymphoma at 6q22.33, and nodular sclerosis Hodgkin lymphoma at 3q28, 6q23.3, 10p14, 13q34, 16p13.13.

Rosalind Eeles and colleagues report meta-analysis of genome-wide association studies for prostate cancer and genotyping on the custom iCOGS array in 25,074 cases and 24,272 controls from 32 studies available in the PRACTICAL Consortium. They identify 23 new prostate cancer susceptibility loci, 20 of which are associated with both aggressive and non-aggressive disease.

Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG methylation sites associated with prostate cancer.

A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Genome-wide association studies (GWAS) have identified hundreds of genomic risk regions for prostate cancer. Here, the authors perform a transcriptome wide association study (TWAS) by incorporating prostate cancer GWAS with gene expression data to identify potential novel prostate cancer risk loci and possible risk mechanisms.

Rosalind Eeles, Christopher Haiman and colleagues report genome-wide association and meta-analyses of prostate cancer in populations of European, African, Japanese and Latino ancestry. They identify 23 new susceptibility loci, including one associated with early-onset prostate cancer.