Multiple loci with different cancer specificities within the 8q24 gene desert.
Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility 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 susceptibility 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.
Ghoussaini
Maya
M
Cancer Research UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, CB1 8RN, Cambridge, UK. maya@srl.cam.ac.uk
Song
Honglin
H
Koessler
Thibaud
T
Al Olama
Ali Amin
AA
Kote-Jarai
Zsofia
Z
Driver
Kristy E
KE
Pooley
Karen A
KA
Ramus
Susan J
SJ
Kjaer
Susanne Krüger
SK
Hogdall
Estrid
E
DiCioccio
Richard A
RA
Whittemore
Alice S
AS
Gayther
Simon A
SA
Giles
Graham G
GG
Guy
Michelle
M
Edwards
Stephen M
SM
Morrison
Jonathan
J
Donovan
Jenny L
JL
Hamdy
Freddie C
FC
Dearnaley
David P
DP
Ardern-Jones
Audrey T
AT
Hall
Amanda L
AL
O'Brien
Lynne T
LT
Gehr-Swain
Beatrice N
BN
Wilkinson
Rosemary A
RA
Brown
Paul M
PM
Hopper
John L
JL
Neal
David E
DE
Pharoah
Paul D P
PD
Ponder
Bruce A J
BA
Eeles
Rosalind A
RA
Easton
Douglas F
DF
Dunning
Alison M
AM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*