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Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.

TitlePleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.
Publication TypeJournal Article
Year of Publication2014
AuthorsCheng I, Kocarnik JM, Dumitrescu L, Lindor NM, Chang-Claude J, Avery CL, Caberto CP, Love S-A, Slattery ML, Chan AT, Baron JA, Hindorff LA, Park SLani, Schumacher FR, Hoffmeister M, Kraft P, Butler AM, Duggan DJ, Hou L, Carlson CS, Monroe KR, Lin Y, Carty CL, Mann S, Ma J, Giovannucci EL, Fuchs CS, Newcomb PA, Jenkins MA, Hopper JL, Haile RW, Conti DV, Campbell PT, Potter JD, Caan BJ, Schoen RE, Hayes RB, Chanock SJ, Berndt SI, Küry S, Bézieau S, Ambite JLuis, Kumaraguruparan G, Richardson DM, Goodloe RJ, Dilks HH, Baker P, Zanke BW, Lemire M, Gallinger S, Hsu L, Jiao S, Harrison TA, Seminara D, Haiman CA, Kooperberg C, Wilkens LR, Hutter CM, White E, Crawford DC, Heiss G, Hudson TJ, Brenner H, Bush WS, Casey G, Le Marchand L
Secondary AuthorsPeters U
JournalGut
Volume63
Issue5
Pagination800-7
Date Published2014 May
ISSN1468-3288
KeywordsAged, Chromosomes, Human, Pair 8, Colorectal Neoplasms, Female, Genetic Markers, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, Logistic Models, Male, Middle Aged, Polymorphism, Single Nucleotide, Principal Component Analysis, Registries, Risk Factors
Abstract

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.

DESIGN: 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.

DOI10.1136/gutjnl-2013-305189
Alternate JournalGut
PubMed ID23935004
PubMed Central IDPMC3918490
Grant ListU01HG004802 / HG / NHGRI NIH HHS / United States
R01 CA042182 / CA / NCI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01 CA059045 / CA / NCI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
R01 CA60987 / CA / NCI NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
U01HG004438 / HG / NHGRI NIH HHS / United States
R01 CA076366 / CA / NCI NIH HHS / United States
U19 CA 055075 / CA / NCI NIH HHS / United States
U01 HG004438 / HG / NHGRI NIH HHS / United States
U01CA98758 / CA / NCI NIH HHS / United States
P01 CA 087969 / CA / NCI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
U01 CA074799 / CA / NCI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R25CA94880 / CA / NCI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U19-CA148107 / CA / NCI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
K05 CA154337 / CA / NCI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
P50 CA 127003 / CA / NCI NIH HHS / United States
U24 CA074783 / CA / NCI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
R01 137178 / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 CA048998 / CA / NCI NIH HHS / United States
R25 CA094880 / CA / NCI NIH HHS / United States
U01 CA137088 / CA / NCI NIH HHS / United States
U01CA136792 / CA / NCI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
U01 HG007376 / HG / NHGRI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
Z01 CP010200 / ImNIH / Intramural NIH HHS / United States
U24 CA074794 / CA / NCI NIH HHS / United States
U01 CA164930 / CA / NCI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U19 CA055075 / CA / NCI NIH HHS / United States
U24 CA097735 / CA / NCI NIH HHS / United States
U01 CA074794 / CA / NCI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
R01 CA48998 / CA / NCI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States
T32 CA009168 / CA / NCI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
R01 CA063464 / CA / NCI NIH HHS / United States
P01 CA033619 / CA / NCI NIH HHS / United States
U01HG004798-01 / HG / NHGRI NIH HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
P30 CA015083 / CA / NCI NIH HHS / United States
R01 CA060987 / CA / NCI NIH HHS / United States
U01 CA097735 / CA / NCI NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
CA42182 / CA / NCI NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
UM1 CA167551 / CA / NCI NIH HHS / United States
U01 CA098758 / CA / NCI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 CA122839 / CA / NCI NIH HHS / United States
R37CA54281 / CA / NCI NIH HHS / United States
K05 CA152715 / CA / NCI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
U01 CA074783 / CA / NCI NIH HHS / United States
U01HG004801-01 / HG / NHGRI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
R01 CA63464 / CA / NCI NIH HHS / United States
U01 CA074806 / CA / NCI NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
U01 CA136792 / CA / NCI NIH HHS / United States
R01HL087641, / HL / NHLBI NIH HHS / United States
P30 CA071789 / CA / NCI NIH HHS / United States
R37 CA054281 / CA / NCI NIH HHS / United States
U01 CA074800 / CA / NCI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
P01CA33619 / CA / NCI NIH HHS / United States
U19 CA148107 / CA / NCI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States