Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

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GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10⁻⁴) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry.

Vyšlo v časopise: Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans. PLoS Genet 7(5): e32767. doi:10.1371/journal.pgen.1001387
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001387

Souhrn

Zdroje

1. Al OlamaAA

Kote-JaraiZ

GilesGG

GuyM

MorrisonJ

2009 Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat Genet 41 1058 1060

2. AmundadottirLT

SulemP

GudmundssonJ

HelgasonA

BakerA

2006 A common variant associated with prostate cancer in European and African populations. Nat Genet 38 652 658

3. EelesRA

Kote-JaraiZ

Al OlamaAA

GilesGG

GuyM

2009 Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet 41 1116 1121

4. EelesRA

Kote-JaraiZ

GilesGG

OlamaAA

GuyM

2008 Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 40 316 321

5. FreedmanML

HaimanCA

PattersonN

McDonaldGJ

TandonA

2006 Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci U S A 103 14068 14073

6. GudmundssonJ

SulemP

GudbjartssonDF

BlondalT

GylfasonA

2009 Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat Genet 41 1122 1126

7. GudmundssonJ

SulemP

ManolescuA

AmundadottirLT

GudbjartssonD

2007 Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet 39 631 637

8. GudmundssonJ

SulemP

RafnarT

BergthorssonJT

ManolescuA

2008 Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat Genet 40 281 283

9. GudmundssonJ

SulemP

SteinthorsdottirV

BergthorssonJT

ThorleifssonG

2007 Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 39 977 983

10. HaimanCA

PattersonN

FreedmanML

MyersSR

PikeMC

2007 Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet 39 638 644

11. TakataR

AkamatsuS

KuboM

TakahashiA

HosonoN

2010 Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat Genet 42 751 754

12. ThomasG

JacobsKB

YeagerM

KraftP

WacholderS

2008 Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet 40 310 315

13. YeagerM

ChatterjeeN

CiampaJ

JacobsKB

Gonzalez-BosquetJ

2009 Identification of a new prostate cancer susceptibility locus on chromosome 8q24. Nat Genet 41 1055 1057

14. YeagerM

OrrN

HayesRB

JacobsKB

KraftP

2007 Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 39 645 649

15. GailMH

2009 Value of adding single-nucleotide polymorphism genotypes to a breast cancer risk model. J Natl Cancer Inst 101 959 963

16. WacholderS

HartgeP

PrenticeR

Garcia-ClosasM

FeigelsonHS

2010 Performance of common genetic variants in breast-cancer risk models. N Engl J Med 362 986 993

17. SunJ

ZhengSL

WiklundF

IsaacsSD

PurcellLD

2008 Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12. Nat Genet 40 1153 1155

18. ZhengSL

StevensVL

WiklundF

IsaacsSD

SunJ

2009 Two independent prostate cancer risk-associated Loci at 11q13. Cancer Epidemiol Biomarkers Prev 18 1815 1820

19. WatersKM

Le MarchandL

KolonelLN

MonroeKR

StramDO

2009 Generalizability of associations from prostate cancer genome-wide association studies in multiple populations. Cancer Epidemiol Biomarkers Prev 18 1285 1289

20. JiaL

LandanG

PomerantzM

JaschekR

HermanP

2009 Functional enhancers at the gene-poor 8q24 cancer-linked locus. PLoS Genet 5 e1000597 doi:10.1371/journal.pgen.1000597

21. Kote-JaraiZ

EastonDF

StanfordJL

OstranderEA

SchleutkerJ

2008 Multiple novel prostate cancer predisposition loci confirmed by an international study: the PRACTICAL Consortium. Cancer Epidemiol Biomarkers Prev 17 2052 2061

22. RafnarT

SulemP

StaceySN

GellerF

GudmundssonJ

2009 Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41 221 227

23. XuJ

ZhengSL

IsaacsSD

WileyKE

WiklundF

2010 Inherited genetic variant predisposes to aggressive but not indolent prostate cancer. Proc Natl Acad Sci U S A 107 2136 2140

24. RobbinsC

TorresJB

HookerS

BonillaC

HernandezW

2007 Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus. Genome Res 17 1717 1722

25. Crowther-SwanepoelD

BroderickP

Di BernardoMC

DobbinsSE

TorresM

2010 Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat Genet 42 132 136

26. EastonDF

PooleyKA

DunningAM

PharoahPD

ThompsonD

2007 Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447 1087 1093

27. GoodeEL

Chenevix-TrenchG

SongH

RamusSJ

NotaridouM

2010 A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet

28. KiemeneyLA

ThorlaciusS

SulemP

GellerF

AbenKK

2008 Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet 40 1307 1312

29. XiaoR

BoehnkeM

2009 Quantifying and correcting for the winner's curse in genetic association studies. Genet Epidemiol 33 453 462

30. ChangBL

SpanglerE

GallagherS

HaimanCA

HendersonBE

2010 Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent. Cancer Epidemiol Biomarkers Prev

31. XuJ

KibelAS

HuJJ

TurnerAR

PruettK

2009 Prostate cancer risk associated loci in African Americans. Cancer Epidemiol Biomarkers Prev 18 2145 2149

32. KolonelLN

HendersonBE

HankinJH

NomuraAM

WilkensLR

2000 A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol 151 346 357

33. SignorelloLB

HargreavesMK

SteinwandelMD

ZhengW

CaiQ

2005 Southern community cohort study: establishing a cohort to investigate health disparities. J Natl Med Assoc 97 972 979

34. GohaganJK

ProrokPC

HayesRB

KramerBS

2000 The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute: history, organization, and status. Control Clin Trials 21 251S 272S

35. CalleEE

RodriguezC

JacobsEJ

AlmonML

ChaoA

2002 The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics. Cancer 94 2490 2501

36. StromSS

GuY

ZhangH

TroncosoP

BabaianRJ

2004 Androgen receptor polymorphisms and risk of biochemical failure among prostatectomy patients. Prostate 60 343 351

37. InglesSA

CoetzeeGA

RossRK

HendersonBE

KolonelLN

1998 Association of prostate cancer with vitamin D receptor haplotypes in African-Americans. Cancer Res 58 1620 1623

38. LiuX

PlummerSJ

NockNL

CaseyG

WitteJS

2006 Nonsteroidal antiinflammatory drugs and decreased risk of advanced prostate cancer: modification by lymphotoxin alpha. Am J Epidemiol 164 984 989

39. AgalliuI

SalinasCA

HanstenPD

OstranderEA

StanfordJL

2008 Statin use and risk of prostate cancer: results from a population-based epidemiologic study. Am J Epidemiol 168 250 260

40. StanfordJL

WicklundKG

McKnightB

DalingJR

BrawerMK

1999 Vasectomy and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 8 881 886

41. RybickiBA

Neslund-DudasC

NockNL

SchultzLR

EklundL

2006 Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism. Cancer Detect Prev 30 412 422

42. PriceAL

PattersonNJ

PlengeRM

WeinblattME

ShadickNA

2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909

43. PriceAL

TandonA

PattersonN

BarnesKC

RafaelsN

2009 Sensitive detection of chromosomal segments of distinct ancestry in admixed populations. PLoS Genet 5 e1000519 doi:10.1371/journal.pgen.1000519