TY - JOUR
T1 - Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis
AU - Whiffin, Nicola
AU - Hosking, Fay J.
AU - Farrington, Susan M.
AU - Palles, Claire
AU - Dobbins, Sara E.
AU - Zgaga, Lina
AU - Lloyd, Amy
AU - Kinnersley, Ben
AU - Gorman, Maggie
AU - Tenesa, Albert
AU - Broderick, Peter
AU - Wang, Yufei
AU - Barclay, Ella
AU - Hayward, Caroline
AU - Martin, Lynn
AU - Buchanan, Daniel D.
AU - Win, Aung Ko
AU - Hopper, John
AU - Jenkins, Mark
AU - Lindor, Noralane M.
AU - Newcomb, Polly A.
AU - Gallinger, Steve
AU - Conti, David
AU - Schumacher, Fred
AU - Casey, Graham
AU - Liu, Tao
AU - Campbell, Harry
AU - Lindblom, Annika
AU - Houlston, Richard S.
AU - Tomlinson, Ian P.
AU - Dunlop, Malcolm G.
PY - 2014/9
Y1 - 2014/9
N2 - To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 [rs1035209; odds ratio (OR) = 1.13, P = 4.54 × 10-11]. We also performed meta-analysis of our studies, with previously published data, of several recently purported CRC risk loci. We failed to find convincing evidence for a previously reported genomewide association at rs11903757 (2q32.3). Of the three additional loci for which evidence of an association in Europeans has been previously described we failed to show an association between rs59336 (12q24.21) and CRC risk. However, for the other two SNPs, our analyses demonstrated new, formally significant associations with CRC. These are rs3217810 intronic in CCND2 (12p13.32; OR = 1.19, P = 2.16 3 10-10) and rs10911251 near LAMC1 (1q25.3; OR = 1.09, P = 1.75 × 10-8). Additionally, we found some evidence to support a relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally identified in East Asians in our European datasets. Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC.
AB - To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 [rs1035209; odds ratio (OR) = 1.13, P = 4.54 × 10-11]. We also performed meta-analysis of our studies, with previously published data, of several recently purported CRC risk loci. We failed to find convincing evidence for a previously reported genomewide association at rs11903757 (2q32.3). Of the three additional loci for which evidence of an association in Europeans has been previously described we failed to show an association between rs59336 (12q24.21) and CRC risk. However, for the other two SNPs, our analyses demonstrated new, formally significant associations with CRC. These are rs3217810 intronic in CCND2 (12p13.32; OR = 1.19, P = 2.16 3 10-10) and rs10911251 near LAMC1 (1q25.3; OR = 1.09, P = 1.75 × 10-8). Additionally, we found some evidence to support a relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally identified in East Asians in our European datasets. Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC.
UR - http://www.scopus.com/inward/record.url?scp=84905646607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905646607&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddu177
DO - 10.1093/hmg/ddu177
M3 - Article
C2 - 24737748
AN - SCOPUS:84905646607
SN - 0964-6906
VL - 23
SP - 4729
EP - 4737
JO - Human molecular genetics
JF - Human molecular genetics
IS - 17
M1 - ddu177
ER -