962 Brief Communications | JNCI Vol. 100, Issue 13 | July 2, 2008
Control subjects were randomly selected
from the Norfolk, UK, component of
EPIC (European Prospective Investigation
of Cancer). Case subjects and control sub-
jects for prostate cancer were also drawn
from the UK population, whereas case
subjects and control subjects for ovarian
cancer were selected from four different
studies from the United Kingdom, United
States, and Denmark. To test the associa-
tion between these nine variants and the
four types of cancer, we performed univar-
iate analysis and compared genotype fre-
quencies in case subjects and control
subjects using unconditional logistic
The data we generated from the above
case – control studies show that there are at
Recently, genome-wide association studies
have been effective at identifying common
genetic variants or single-nucleotide poly-
morphisms (SNPs) associated with com-
mon disease risk without any presumption
about their localization or function. Recent
studies have identifi ed and confi rmed asso-
ciations of breast, prostate, and colorectal
cancer with several variants within a 600-
Kb region of a longer, 1.18-Mb, sequence
that does not code for any known genes on
chromosome 8q24 ( 1 – 10 ). Large chromo-
somal regions devoid of genes (often
referred to as gene deserts) have been dis-
covered to be associated with several dis-
eases, indicating that they may have a
function. Here, we have genotyped the nine
SNPs across the region: rs13254738,
rs7000448, and rs1447295 (or a good sur-
rogate SNP for each fourth footnote to
Table 1) in four large case – control sets of
prostate (1854 case subjects and 1894 con-
trol subjects), breast (2270 case subjects
and 2280 control subjects), colorectal (2299
case subjects and 2284 control subjects),
and ovarian (1975 case subjects and 3411
control subjects) cancer ( Table 1 and
Supplementary Table 1 ). Case subjects
with colorectal and breast cancer were
drawn from SEARCH, an ongoing popu-
lation-based study in East Anglia, UK.
Multiple Loci With Different Cancer
Specificities Within the 8q24 Gene Desert
Maya Ghoussaini , Honglin Song , Thibaud Koessler , Ali Amin Al Olama ,
Zsofia Kote-Jarai , Kristy E. Driver , Karen A. Pooley , Susan J. Ramus ,
Susanne Krüger Kjaer , Estrid Hogdall , Richard A. DiCioccio , Alice S. Whittemore ,
Simon A. Gayther , Graham G. Giles , Michelle Guy , Stephen M. Edwards ,
Jonathan Morrison , Jenny L. Donovan , Freddie C. Hamdy , David P. Dearnaley ,
Audrey T. Ardern-Jones , Amanda L. Hall , Lynne T. O’Brien , Beatrice N. Gehr-
Swain , Rosemary A. Wilkinson , Paul M. Brown , John L. Hopper , David E. Neal ,
Paul D. P. Pharoah , Bruce A. J. Ponder , Rosalind A. Eeles , Douglas F. Easton ,
Alison M. Dunning; for the UK Genetic Prostate Cancer Study Collaborators/
British Association of Urological Surgeons’ Section of Oncology and the UK
ProtecT Study Collaborators
Recent studies based on genome-wide association, linkage, and admixture scan
analysis have reported associations of various genetic variants in 8q24 with sus-
ceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-
Mb region that contains no known genes but is bounded at its centromeric end
by FAM84B and at its telomeric end by c-MYC , two candidate cancer susceptibil-
ity genes. To investigate the associations of specific loci within 8q24 with specific
cancers, we genotyped the nine previously reported cancer-associated single-
nucleotide polymorphisms across the region in four case – control sets of prostate
(1854 case subjects and 1894 control subjects), breast (2270 case subjects and
2280 control subjects), colorectal (2299 case subjects and 2284 control subjects),
and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different
haplotype blocks within this gene desert were specifically associated with risks of
different cancers. One block was solely associated with risk of breast cancer,
three others were associated solely with the risk of prostate cancer, and a fifth
was associated with the risk of prostate, colorectal, and ovarian cancer, but not
breast cancer. We conclude that there are at least five separate functional variants
in this region.
J Natl Cancer Inst 2008;100: 962 – 966
Affiliations of authors: Cancer Research UK
Department of Oncology (MG, HS, TK, KED, KAP,
PDPP, BAJP, AMD), Cancer Research UK Genetic
Epidemiology Unit, Department of Public Health
and Primary Care (AAAO, JM, DFE), University of
Cambridge, Strangeways Research Laboratory,
Cambridge, UK; The Institute of Cancer Research,
Sutton, Surrey, UK (ZKJ, MG, SME, DPD, ALH,
LTO’, BNGS, RAW, RAE); Translational Research
Laboratories, Institute for Women ’ s Health,
University College London, London, UK (SJR,
SAG); Institute of Cancer Epidemiology, Danish
Cancer Society, Copenhagen, Denmark (SKK,
EH); Department of Cancer Genetics, Roswell
Park Cancer Institute, Buffalo, NY (RAD);
Department of Health Research and Policy,
Stanford University School of Medicine,
Stanford, CA (ASW); Cancer Epidemiology
Centre, The Cancer Council Victoria, Carlton,
Molecular, Environmental, Genetic and Analytic
Epidemiology, The University of Melbourne,
Carlton, Victoria, Australia
Department of Social Medicine, University of
Bristol, Bristol, UK (JLD); Academic Urology
Unit, University of Sheffield, Sheffield, UK
(FCH); The Royal Marsden NHS Foundation
Trust, Sutton, Surrey, UK (DPD, ATAJ,
ALH, BNGS, RAE); The Royal Marsden NHS
Foundation Trust, London, UK (DPD, ATAJ,
ALH, BNGS, RAE); Surgical Oncology (Uro-
Oncology: S4), University of Cambridge,
Addenbrooke’s Hospital, UK (DEN); Cancer
Research UK Cambridge Cancer Research
Institute, Cambridge, UK (BAJP) .
(GGG); Centre for
Correspondence to: Maya Ghoussaini, PhD, CR-
UK Department of Oncology, University of
Cambridge, Strangeways Research Laboratory,
Worts Causeway, CB1 8RN, Cambridge, UK
(e-mail: firstname.lastname@example.org ).
See “Funding” and “Notes” following “References.”
© The Author 2008. Published by Oxford University
Press. All rights reserved. For Permissions, please
JNCI | Brief Communications 963
least fi ve different cancer susceptibility loci
within the 8q24 “desert,” each separated
from the others by recombination hot spots
and each specifi c for cancer of particular
tissue type ( Table 1 and Figure 1, A ).
Region 1, the most centromeric block,
spans base positions 128.14 – 128.28 Mb
(NCBI Build 35). SNP rs16901979 (1.3,
Table 1 ) was reported to be associated with
prostate cancer by two independent studies
( 4 , 5 ). More recently, rs13254738 (1.1) and
rs6983561 (1.2) have also been found to be
associated with prostate cancer ( 5 ).
However, SNPs 1.2 and 1.3 are highly cor-
related; thus, they refl ect the same associa-
tion ( Figure 1, B ). We confi rmed the
association of these SNPs with prostate
cancer (odds ratio [OR] = 1.12, 95% confi -
dence interval [CI] = 1.01 to 1.24, P value
from Cochran Armitage test for trend =
0.029 for rs13254738; OR = 2.11, 95%
CI = 1.65 to 2.71, P value = 1.4 × 10 –9 for
rs6983561; and OR = 2.06, 95% CI = 1.61
to 2.65, P value = 4.9 × 10 –9 for rs16901979)
but found no evidence for their association
with risks of breast, colorectal, or ovarian
cancers. The only published study that
addressed the association of these SNPs with
risk of colon cancer also found no evidence
for an association ( 6 ). To our knowledge, no
other studies have specifi cally addressed the
association of these SNPs with breast, ovar-
ian, or other cancer types. Thus, variants in
region 1 appear to be specifi cally associated
with the risk of prostate cancer.
Region 2, spanning base positions
128.35 – 128.51Mb, was fi rst identifi ed as a
potential breast cancer susceptibility locus
by a genome-wide scan; this identifi cation
was confi rmed by a study of 21 860 case
subjects and 22 578 control subjects ( 2 ). In
follow-up fi ne mapping, we have studied 23
SNPs that tag the common variation in this
haplotype block in the SEARCH study.
None of these SNPs showed a stronger
association with breast cancer than that
shown by the original tag SNP rs13281615
(data not shown). This SNP (2.1, Table 1 )
was not associated with prostate, colorectal,
or ovarian cancer. To date, the only pub-
lished study that tested the association of
these SNPs with risks of other cancers
(prostate and colorectal) found no evidence
of an association ( 6 ). Taken together, these
data suggest that region 2 is specifi c for
breast cancer susceptibility.
Region 3, spanning base positions
128.47 – 128.54 Mb, was originally detected
in African Americans by an admixture scan
(a method for localizing disease-causing
genetic variants that differ in frequency
across populations) for prostate cancer
(Table 1, rs6983267, 3.3; rs7000448, 4.1)
( 5 ). Subsequently, two genome-wide scans
found that SNP 3.3 and rs10505477 (3.1)
( 8 , 10 ) were associated with colorectal
cancer, and these associations have been
consistently replicated in independent
case – control studies ( 6 , 8 , 10 , 11 ). Another
SNP in the same block, rs10808556 (3.2),
has also been associated with colorectal
cancer ( 6 ). We found that SNPs 3.1, 3.2,
and 3.3 were all associated with risks of
prostate (OR = 1.43, 95% CI = 1.30 to 1.56,
P value = 7.7 × 10 –14 ), colorectal (OR = 1.27,
95% CI = 1.16 to 1.37, P value = 3.6 × 10 –8 ),
and ovarian cancers (OR = 1.11, 95% CI =
1.03 to 1.23, P value = 9.9 × 10 –3 ) (ORs,
95% CIs, and P values are given for SNP
3.2). This is the strongest evidence, to date,
reporting an association between ovarian
cancer risk and a common allele. The three
SNPs in this block are highly correlated
with each other in control subjects ( r 2 val-
ues >0.65, Figure 1, B ). Using stepwise
logistic regresison, the associations for
each disease could be explained by a single
SNP (data not shown). We found no
evidence that one of these SNPs was more
strongly associated with risk of prostate
and colon cancer than the other two. It is
therefore likely that there is common
underlying factor that increases the risk of
the three cancers. None of the SNPs in
this region were associated with breast
cancer risk. Our data suggest that the
prostate, colorectal, and ovarian cancer
locus is smaller than the one originally
defi ned ( 5 ) and only spans base positions
128.47 – 128.50 Mb. Therefore, we have
designated the remaining portion of the
original locus, spanning positions 128.50 –
128.54 Mb, as region 4.
Region 4 (prostate cancer) contains SNP
rs7000448 (4.1), which has been shown to
be associated with prostate cancer ( 5 ). This
SNP is only weakly correlated with the
region 3 and region 5 SNPs ( r 2 < 0.13,
Figure 1, B ). Furthermore, we confi rmed
an association of this variant with prostate
cancer risk (OR = 1.23, 95% CI = 1.11 to
1.35, P value = 2.8 × 10 –5 ) but found no
association with risks of colorectal, ovarian,
or breast cancers, suggesting that this is a
separate prostate cancer – specifi c locus.
Region 5 is the closest of the fi ve regions
to the c-MYC oncogene and spans base
positions 128.54 – 128.62Mb.
rs1447295 (5.1, Table 1 ) was originally
found to be associated with prostate cancer
through linkage and association analyses in
the Icelandic population ( 1 ). This association
has subsequently been replicated in other
populations ( 3 , 7 , 9 , 12 , 13 ). A second SNP,
rs10090154, which is perfectly correlated
with rs1447295 (5.1) in Europeans ( r 2 = 1 in
CEU HapMap) but not in Africans ( r 2 ≥
0.64), was subsequently identifi ed ( 5 ). A
weak association of rs10090154 with
colorectal cancer was reported as provi-
sional, pending independent confi rmation
( 6 ). We found SNP 5.1 (rs1447295) to be
statistically signifi cantly associated with
prostate cancer (OR = 1.86, 95% CI= 1.60
to 2.15, P value = 6.9 × 10 –17 ) but not with
breast, colorectal, or ovarian cancer. A
large study, nested in seven US and
European cohorts, has also noted the
CONTEXT AND CAVEATS
Genetic variants in a region of chromo-
some 8 had been associated with the risk of
breast, colorectal, and prostate cancer.
Case subjects with each of four cancers
(breast, colorectal, prostate, and ovarian)
and control subjects were examined for the
presence of previously identified risk vari-
ants that span the chromosomal region
previously associated with cancer risk.
Genotype frequencies were compared using
unconditional logistic regression.
At least five distinct cancer susceptibility
loci were found within the chromosomal
region, each separated by recombination
hot spots and specific for one or more of
the four cancers.
Fine mapping of the identified loci may
help elucidate molecular mechanisms that
contribute to carcinogenesis.
It is unknown whether any of the cancer-
associated polymorphisms examined are
causal variants or simply markers of
unknown causal variants.
964 Brief Communications | JNCI Vol. 100, Issue 13 | July 2, 2008
absence of association of this SNP with
breast cancer susceptibility ( 7 ).
To date, three risk-associated regions at
8q24 (regions 1, 3, and 5) have been
reported to confer independent risks of
prostate cancer. In this study, we found a
total of eight SNPs, distributed across
four regions, to be associated with the
risk of prostate cancer. To test how many
of these associations were independent,
we performed a stepwise logistic reg -
ression that included all eight SNPs in the
model. Five SNPs (two in region 1 and
one in each of regions 3, 4, and 5) were
independently associated with prostate
cancer (rs13254738, P = .008; rs6983561,
P = 1.6 × 10 –7 ; rs6983267, P = 1.6 × 10 –7 ;
rs7000448, P = .022; rs1447295, P = 2.0 ×
10 –13 ). Theoretically, each of these inde-
pendent SNPs may be markers for a sepa-
rate causative factor in prostate cancer
Thus, we have shown there are at least
fi ve independent loci within this gene des-
ert with different associations with particu-
lar cancers. Further studies of the region
may identify additional loci associated with
specifi c cancers and possibly refi ne our
understanding of the mechanisms underly-
ing the associations reported here. A recent
publication has reported that none of the
above SNPs were associated with risk of
endometrial cancer ( 14 ).
The biologic mechanisms underlying
these associations with different cancers are
unknown. This region is a frequent site of
somatic amplifi cation in several cancers
( 15 , 16 ). It is possible that these variants
affect tissue-specifi c enhancers in the
region, thus altering expression of one or
more genes an unknown distance away.
The known genes that are closest to 8q24
are FAM84B and c-MYC . Overexpression
of c-MYC occurs in both breast and pros-
tate cancers ( 17 – 19 ), and reduction of
c-MYC expression by RNA interference
inhibits tumor growth both in vivo and in
vitro ( 20 ). FAM84B is described as a breast
cancer membrane-associated protein, but
little more is known about its function ( 18 ).
However, SNPs located in the c-MYC and
FAM84B genes were not found to be asso-
ciated with prostate
Furthermore, SNPs in regions 1, 3, and 5
cancer ( 1 , 4 ).
Table 1 . Association of 8q24 single nucleotide polymorphisms with colorectal, ovarian, breast, and prostate cancer *
Colorectal cancer † Ovarian cancerBreast cancer Prostate cancer
OR (95% CI) P value ‡ OR (95% CI) P value ‡ OR (95% CI) P value ‡ OR (95% CI) P value ‡
(1.1) (region 1,
(1.2) (region 1,
(1.3) (region 1,
(2.1) (region 2,
(3.1) (region 3,
(3.2) (region 3,
rs6983267 § (A/G)
(3.3) (region 3,
(4.1) (region 4,
(5.1) (region 5,
(0.99 to 1.13)
(0.94 to 1.11)
(0.88 to 1.05)
(1.01 to 1.24)
(0.81 to 1.11)
(0.72 to 1.13)
(0.77 to 1.21)
(1.65 to 2.71)
1.4 × 10 ? 9
G (0.97) 0.89
(0.77 to 1.06)
(0.71 to 1.11)
(0.80 to 1.25)
(1.61 to 2.65)
4.9 × 10 ? 9
A (0.60) 0.94
(0.89 to 1.00)
(0.91 to 1.07)
(1.11 to 1.32)
1 × 10 ? 5 0.95
(0.87 to 1.05)
(1.19 to 1.33)
2.9 × 10 ? 8
(1.04 to 1.23)
2.0 × 10 ? 3 0.96
(0.88 to 1.04)
(1.30 to 1.56)
7.7 × 10 ? 14
(1.16 to 1.37)
5.1 × 10 ? 8
(1.04 to 1.22)
1.7 × 10 ? 3 0.99
(0.91 to 1.08)
(1.19 to 1.44)
4.2 × 10 ? 8
(1.16 to 1.37)
3.6 × 10 ? 8
(1.03 to 1.20)
9.9 × 10 ? 3 0.97
(0.89 to 1.05)
(1.30 to 1.56)
7.7 × 10 ? 14
(0.98 to 1.11)
(0.96 to 1.13)
(0.88 to 1.05)
(1.11 to 1.35)
2.8 × 10 ? 5
(0.89 to 1.08)
( 0.93 to 1.22)
(0.80 to 1.07)
(1.60 to 2.15)
6.9 × 10 ? 17
* Genotype results were obtained for more than 95% of all subjects. rs10090154 was not evaluated because it was perfectly correlated with rs1447295 in our
European population sample. All genotyping was performed by Taqman assay unless otherwise indicated. No deviation from Hardy – Weinberg
equilibrium was observed in the genotype distributions of the control subjects for any of the SNPs. OR = odds ratio; CI = confidence interval; SNP = single
nucleotide polymorphism. The bold font refers to significant P values ( P < .05) and their corresponding OR.
† Sample sets consisted of 2299 colorectal cancer case subjects and 2284 control subjects, 1975 ovarian cancer case subjects and 3411 control subjects, 2270
breast cancer case subjects and 2280 control subjects, 1854 prostate cancer case subjects and 1894 control subjects.
‡ P value from the Cochran – Armitage trend test.
§ Genotyped in the prostate study using the illumina 550K chip covering approximately 550 000 SNPs across the genome. Hence, the SNPs were replaced by
alternative tags on the illumina chip: rs13281615 by rs672888 ( r 2 = 0.97) and rs10505477 by rs6983267 ( r 2 = 0.93).
JNCI | Brief Communications 965
found to be associated with prostate cancer
do not appear to be associated with changes
in expression of these genes in prostate or
colorectal tumors ( 1 , 4 , 10 ). Several other
genes were predicted to exist in 8q24 ( 1 , 10 ),
although there is no evidence for any
protein-coding transcripts ( 1 , 10 ). One is a
putative pseudogene of the transcription
factor POU5F1P1 in region 3. One study
has confi rmed the expression of this tran-
script in cancer tissues, including colon
cancer, although its physiological role is
unknown ( 8 ).
Despite their strong associations with
cancer, it is not known whether the SNPs
tested here are causal variants or are simply
markers that are correlated with the causal
variants in each region. Resequencing and
fi ne mapping of each of the haplotype
blocks, followed by functional characteriza-
tion studies, may ultimately identify the
causal variants and reveal their mechanisms
in cancer susceptibility and pathogenesis. If
this 8q24 locus is truly a gene desert, it
points to a very long-range mode of action
for these variants that had previously been
1. Amundadottir LT , Sulem P , Gudmundsson J .
A common variant associated with prostate
cancer in European and African populations .
Nat Genet. 2006 ; 38 ( 6 ) : 652 – 658 .
2. Easton DF , Pooley KA , Dunning AM , et al .
Genome-wide association study identifi es
novel breast cancer susceptibility loci . Nature .
2007 ; 447 ( 7148 ) : 1087 – 1093 .
3. Freedman ML , Haiman CA , Patterson N ,
et al . Admixture mapping identifi es 8q24 as a
prostate cancer risk locus in African-American
men . Proc Natl Acad Sci USA . 2006 ; 103 ( 38 ) :
14068 – 14073 .
4. Gudmundsson J , Sulem P , Manolescu A , et al .
Genome-wide association study identifi es a
second prostate cancer susceptibility variant at
8q24 . Nat Genet. 2007 ; 39 ( 5 ) : 631 – 637 .
5. Haiman CA , Patterson N , Freedman ML ,
et al . Multiple regions within 8q24 indepen-
dently affect risk for prostate cancer . Nat Genet.
2007 ; 39 ( 5 ) : 638 – 644 .
6. Haiman CA , Le Marchand L , Yamamato J ,
et al . A common genetic risk factor for colorec-
tal and prostate cancer . Nat Genet. 2007 ; 39 ( 8 ) :
954 – 956 .
7. Schumacher FR , Feigelson HS , Cox DG , et al .
A common 8q24 variant in prostate and breast
cancer from a large nested case-control study .
Cancer Res. 2007 ; 67 ( 7 ) : 2951 – 2956 .
8. Tomlinson I , Webb E , Carvajal-Carmona L ,
et al . A genome-wide association scan of tag
SNPs identifi es a susceptibility variant for
colorectal cancer at 8q24.21 . Nat Genet. 2007 ;
39 ( 8 ) : 984 – 988 .
9. Yeager M , Orr N , Hayes RB , et al . Genome-
wide association study of prostate cancer
identifi es a second risk locus at 8q24 . Nat Genet.
2007 ; 39 ( 5 ) : 645 – 649 .
10. Zanke BW , Greenwood CM , Rangrej J , et al .
Genome-wide association scan identifi es a
colorectal cancer susceptibility locus on chro-
mosome 8q24 . Nat Genet. 2007 ; 39 ( 8 ) : 989 – 994 .
11. Gruber SB , Moreno V , Rozek LS , et al .
Genetic variation in 8q24 associated with
risk of colorectal cancer . Cancer Biol Ther .
2007 ; 6 ( 7 ) : 1143 – 1147 .
Figure 1 . A ) Haploview output of the 1.18-Mb 8q24 “desert” showing the fi ve cancer-specifi c regions reported to date. Approximate positions of
the genes POU5F1P1 , c-MYC , and FAM84B are indicated. Correlations between single nucleotide polymorphisms (SNPs) in the region are indi-
cated. Darker squares = stronger correlations. B ) Correlations ( r 2 ) between SNPs with data in Table 1 . Darker shading corresponds to stronger
correlations between SNPs.
966 Brief Communications | JNCI Vol. 100, Issue 13 | July 2, 2008
12. Severi G , Hayes VM , Padilla EJ , et al . The
common variant rs1447295 on chromosome
8q24 and prostate cancer risk: results from an
Australian population-based case-control study .
Cancer Epidemiol Biomarkers Prev . 2007 ; 16 ( 3 ) :
610 – 612 .
13. Zheng SL , Sun J , Cheng Y , et al . Association
between two unlinked loci at 8q24 and pros-
tate cancer risk among European Americans .
J Natl Cancer Inst . 2007 ; 99 ( 20 ) : 1525 – 1533 .
14. Setiawan VW , Ursin G , Horn-Ross PL , et al .
Germ line variation at 8q24 and endometrial
cancer risk . Cancer Epidemiol Biomarkers Prev .
2007 ; 16 ( 10 ) : 2166 – 2168 .
15. Buness A , Kuner R , Ruschhaupt M , Poustka A ,
Sultmann H , Tresch A . Identifi cation of aber-
rant chromosomal regions from gene expres-
sion microarray studies applied to human breast
cancer . Bioinformatics . 2007 ; 23 ( 17 ) : 2273 – 2280 .
16. Van Den BC , Guan XY , Von Hoff D , et al .
DNA sequence amplifi cation in human pros-
tate cancer identifi ed by chromosome micro-
dissection: potential prognostic implications .
Clin Cancer Res. 1995 ; 1 ( 1 ) : 11 – 18 .
17. Sears RC . The life cycle of C-myc : from syn-
thesis to degradation . Cell Cycle . 2004 ; 3 ( 9 ) :
1133 – 1137 .
18. Buttyan R , Sawczuk IS , Benson MC , Siegal JD ,
Olsson CA . Enhanced expression of the c-myc
protooncogene in high-grade human prostate
cancers . Prostate . 1987 ; 11 ( 4 ) : 327 – 337 .
19. Nupponen NN , Kakkola L , Koivisto P ,
Visakorpi T . Genetic alterations in hormone-
refractory recurrent prostate carcinomas . Am
J Pathol . 1998 ; 153 ( 1 ) : 141 – 148 .
20. Wang YH , Liu S , Zhang G , et al . Knockdown
of c-Myc expression by RNAi inhibits MCF-7
breast tumor cells growth in vitro and in vivo .
Breast Cancer Res. 2005 ; 7 ( 2 ) : R220 – R228 .
This work was supported by Cancer Research UK.
The ProtecT study which provided control subjects
for the prostate analyses is funded by the Health
Technology Assessment Programme (projects
96/20/06, 96/20/99). We would also like to thank
the following for funding support: The Institute of
Cancer Research and The Everyman Campaign,
The Prostate Cancer Research Foundation,
Prostate Research Campaign UK, The National
Cancer Research Network UK, and The National
Cancer Research Institute UK and grants from the
National Health and Medical Research Council,
Australia (209057, 251533, 450104); VicHealth; The
Cancer Council Victoria; The Whitten Foundation;
Tattersall’s; The Roswell Park Alliance; The Danish
Cancer Society; National Cancer Institute (CA71766
and Core Grant CA16056 and RO1 CA61107); and
Fondation Dr Dubois-Ferrière Dinu Lipatti.
H. Song, T. Koessler, and A. A. A. Olama contrib-
uted equally to the work.
List of members of The UK Genetic Prostate
Cancer Study Collaborators/British Association of
Urological Surgeons’ Section of Oncology is avail-
able on request.
UK ProtecT Study Collaborators: Prasad
Bollina, Sue Bonnington, Debbie Cooper,
Andrew Doble, Alan Doherty, Garett Durkan,
Emma Elliott, David Gillatt, Pippa Herbert, Peter
Holding, Joanne Howson, Mandy Jones, Roger
Kockelbergh, Howard Kynaston, Teresa Lennon,
Norma Lyons, Hing Leung, Hilary Moody, Philip
Powell, Stephen Prescott, Pauline Thompson —
Care of Surgical Oncology (Uro-Oncology:S4),
University of Cambridge, Box 279, Addenbrooke’s
Hospital, Hills Road, Cambridge, UK.
We would like to thank all the patients and con-
trol subjects who took part in this study. We would
also like to thank Hannah Munday, Barbara Perkins,
Helen Imogen Field, Mitul Shah, Clare Jordan,
Judy West, Anabel Simpson, Sue Irvine, the search
team: the local general practices and nurses and the
East Anglian Cancer Registry for recruitment of the
UK case subjects and the EPIC-Norfolk investiga-
tors for recruitment of the UK control subjects;
Claus K. Høgdall and Jan Blaakaer for their addi-
tional contribution to the MALignant OVArian
cancer collection; Aleksandra Gentry-Maharaj, Eva
Wozniak, Usha Menon, and the UK Ovarian-can-
cer Population Study (UKOPS) team of research
nurses for their contribution to the UKOPS ovarian
cancer collection (funded by the OAK foundation).
D. F. Easton is a principal research fellow of Cancer
Research UK, P. D. P. Pharoah is Cancer Research
UK senior clinical research fellow, and B. A. J.
Ponder is a Gibb fellow of CRUK. J. L. Hopper is an
Australia fellow of the National Health and Medical
Research Council. The authors had full responsibil-
ity for the analysis and interpretation of the data and
for the writing and submission of the manuscript.
Manuscript received November 27 , 2007 ;
revised April 20 , 2008 ; accepted May 14 , 2008 .