Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.
OBJECTIVE
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer.


METHODS
We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations.


RESULTS
Two correlated SNPs--rs10090154 and rs4242382--in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites.


CONCLUSIONS
This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.
Cancer Prevention Institute of California, Fremont, California, USA.
Iona
I
Cheng
Jonathan M
JM
Kocarnik
Logan
L
Dumitrescu
Noralane M
NM
Lindor
Jenny
J
Chang-Claude
Christy L
CL
Avery
Christian P
CP
Caberto
Shelly-Ann
SA
Love
Martha L
ML
Slattery
Andrew T
AT
Chan
John A
JA
Baron
Lucia A
LA
Hindorff
Sungshim Lani
SL
Park
Fredrick R
FR
Schumacher
Michael
M
Hoffmeister
Peter
P
Kraft
Anne M
AM
Butler
David J
DJ
Duggan
Lifang
L
Hou
Chris S
CS
Carlson
Kristine R
KR
Monroe
Yi
Y
Lin
Cara L
CL
Carty
Sue
S
Mann
Jing
J
Ma
Edward L
EL
Giovannucci
Charles S
CS
Fuchs
Polly A
PA
Newcomb
Mark A
MA
Jenkins
John L
JL
Hopper
Robert W
RW
Haile
David V
DV
Conti
Peter T
PT
Campbell
John D
JD
Potter
Bette J
BJ
Caan
Robert E
RE
Schoen
Richard B
RB
Hayes
Stephen J
SJ
Chanock
Sonja I
SI
Berndt
Sebastien
S
Küry
Stephane
S
Bézieau
Jose Luis
JL
Ambite
Gowri
G
Kumaraguruparan
Danielle M
DM
Richardson
Robert J
RJ
Goodloe
Holli H
HH
Dilks
Paxton
P
Baker
Brent W
BW
Zanke
Mathieu
M
Lemire
Steven
S
Gallinger
Li
L
Hsu
Shuo
S
Jiao
Tabitha A
TA
Harrison
Daniela
D
Seminara
Christopher A
CA
Haiman
Charles
C
Kooperberg
Lynne R
LR
Wilkens
Carolyn M
CM
Hutter
Emily
E
White
Dana C
DC
Crawford
Gerardo
G
Heiss
Thomas J
TJ
Hudson
Hermann
H
Brenner
William S
WS
Bush
Graham
G
Casey
Loïc
L
Le Marchand
Ulrike
U
Peters
D000368:Aged; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012042:Registries; D012307:Risk Factors
D005819:Genetic Markers
COLORECTAL CANCER; EPIDEMIOLOGY; POLYMORPHIC VARIATION