Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

@article{Rand2016WholeexomeSO,
  title={Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.},
  author={Kristin A. Rand and Nadin Rohland and Arti Tandon and Alexander Stram and Xin Sheng and Ron Do and Bogdan Pasaniuc and Alexander Allen and Dominique Quinque and Swapan Mallick and Lo{\"i}c Le Marchand and Sam Kaggwa and Alex Lubwama and Daniel O. Stram and Stephen Watya and Brian E. Henderson and David V. Conti and David Reich and Christopher A. Haiman},
  journal={Human molecular genetics},
  year={2016},
  volume={25 2},
  pages={
          371-81
        }
}
Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034… 

Tables from this paper

Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations.

TLDR
Systematic genomic sequencing of prostate cancer in African-American men revealed new insights into prostate cancer, including the identification of ERF as a prostate cancer gene; somatic copy-number alteration differences; and uncommon PIK3CA and PTEN alterations.

Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities

TLDR
A review examines the progress of understanding in CaP genetics and genomics and highlights the need to increase the representation from minority populations.

Inherited Predisposition to Prostate Cancer: From Gene Discovery to Clinical Impact.

  • K. Cooney
  • Biology, Medicine
    Transactions of the American Clinical and Climatological Association
  • 2017
TLDR
This research team studied a large number of families with linkage evidence to chromosome 17q21-22 and ultimately identified a recurrent mutation in the HOXB13 gene that accounts for ~5% of hereditary prostate cancer families.

Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort

TLDR
The aim of the study was to identify rare single nucleotide variants and small indels in 40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases and 1,006 unrelated controls using a robust and cost-effective DNA pooling NGS strategy.

Heritability of prostate cancer: a tale of rare variants and common single nucleotide polymorphisms.

TLDR
This meta-analysis included 51 cohort studies and found a dichotomized association between smoking and PCa risk and found current smoking was associated with an increased risk of PCa and a reduced risk in studies completed in 1995 or earlier.

Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes

TLDR
It is shown that only 13 of the 46 DDRGs identified with pathogenic/likely pathogenic mutations are present in both African American and European ancestry patients, and RAD family genes, which are potentially targetable, are among the most frequently mutated DDRGs in African American, but not in European Ancestry patients.

Exome-Wide Pan-Cancer Analysis of Germline Variants in 8,719 Individuals Finds Little Evidence of Rare Variant Associations

TLDR
This study investigated associations between rare variants and 14 cancer types and provided little evidence in favor of the rare variant hypothesis, suggesting much larger sample sizes may be needed to detect undiscovered rare cancer variants.

A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer

TLDR
A systematic literature review of cancer genetic susceptibility studies that used NGS technologies at an exome/genome-wide scale to obtain a fuller understanding of the research landscape to date and to inform future studies found the untapped potential in conducting studies with appropriately sized and racially diverse families and populations is pointed to.

Inflammatory metabolic profile of South African patients with prostate cancer

TLDR
A portrait of the metabolic changes in African men with PCa has been delineated indicating a strong association between inflammation and metabolic profiles, and how the metabolic profile could be used to identify those patients with high level of inflammation, characterized by aggressive PCa and short life expectancy.

References

SHOWING 1-10 OF 63 REFERENCES

A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer

TLDR
A new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] is identified and its association remains significant after adjustment for all known risk-associated variants.

Generalizability of established prostate cancer risk variants in men of African ancestry

TLDR
Examining previously reported risk variants in men of African ancestry indicates common functional alleles that are shared across populations, and further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African Ancestry.

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

TLDR
A new risk variant on chromosome 17q21 is identified, ∼5% in men of African descent, whereas it is rare in other populations (<1%).

The contribution of rare variation to prostate cancer heritability

We report targeted sequencing of 63 known prostate cancer risk regions in a multi-ancestry study of 9,237 men and use the data to explore the contribution of low-frequency variation to disease risk.

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

TLDR
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.

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

TLDR
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.

HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG)

TLDR
It is demonstrated that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.

Multiple regions within 8q24 independently affect risk for prostate cancer

TLDR
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.

Germline mutations in HOXB13 and prostate-cancer risk.

TLDR
The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer, and this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this common cancer.

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

TLDR
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.
...