Genetic Variants in XRCC2: New Insights Into Colorectal Cancer Tumorigenesis

TY - JOUR

T1 - Genetic Variants in XRCC2: New Insights Into Colorectal Cancer Tumorigenesis

A1 - Curtin,Karen

A1 - Lin,Wei-Yu

A1 - George,Rina

A1 - Katory,Mark

A1 - Shorto,Jennifer

A1 - Cannon-Albright,Lisa A.

A1 - Smith,Gillian

A1 - Bishop,D. Timothy

A1 - Cox,Angela

A1 - Camp,Nicola J.

A1 - Colorectal Canc Study Grp

AU - Curtin,Karen

AU - Lin,Wei-Yu

AU - George,Rina

AU - Katory,Mark

AU - Shorto,Jennifer

AU - Cannon-Albright,Lisa A.

AU - Smith,Gillian

AU - Bishop,D. Timothy

AU - Cox,Angela

AU - Camp,Nicola J.

AU - Colorectal Canc Study Grp

PY - 2009/9

Y1 - 2009/9

N2 - <p>Polymorphisms in DNA double-strand break repair gene XRCC2 may play an important role in colorectal cancer etiology, specifically in disease subtypes. Associations of XRCC2 variants and colorectal cancer were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, and Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases and 1,422 controls). The 14 variants studied were tagging single nucleotide polymorphisms (SNP) selected from National Institute of Environmental Health Sciences/HapMap data supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple colorectal cancer groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta-analyses of the total resource that includes family-based data. Similar to reports of colorectal cancer and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G&gt;C, with increased risk of rectal tumors (odds ratio, 2.1; 95% confidence interval, 1.3-3.3; P-chi 2 = 0.0006) versus controls, with the largest risk found for female rectal cases (odds ratio, 3.1; 95% confidence interval, 1.6-6.1; P-chi 2 = 0.0006). This difference was significantly different to that for proximal and distal colon cancers (P-chi 2 = 0.02). Our investigation supports a role for XRCC2 in colorectal cancer tumorigenesis, conferring susceptibility to rectal tumors. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2476-84)</p>

AB - <p>Polymorphisms in DNA double-strand break repair gene XRCC2 may play an important role in colorectal cancer etiology, specifically in disease subtypes. Associations of XRCC2 variants and colorectal cancer were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, and Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases and 1,422 controls). The 14 variants studied were tagging single nucleotide polymorphisms (SNP) selected from National Institute of Environmental Health Sciences/HapMap data supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple colorectal cancer groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta-analyses of the total resource that includes family-based data. Similar to reports of colorectal cancer and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G&gt;C, with increased risk of rectal tumors (odds ratio, 2.1; 95% confidence interval, 1.3-3.3; P-chi 2 = 0.0006) versus controls, with the largest risk found for female rectal cases (odds ratio, 3.1; 95% confidence interval, 1.6-6.1; P-chi 2 = 0.0006). This difference was significantly different to that for proximal and distal colon cancers (P-chi 2 = 0.02). Our investigation supports a role for XRCC2 in colorectal cancer tumorigenesis, conferring susceptibility to rectal tumors. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2476-84)</p>

KW - STRAND BREAK REPAIR

KW - SINGLE-NUCLEOTIDE POLYMORPHISMS

KW - EPITHELIAL OVARIAN-CANCER

KW - MICROSATELLITE INSTABILITY

KW - MISMATCH-REPAIR

KW - DNA-DAMAGE

KW - COLON-CANCER

KW - HOMOLOGOUS RECOMBINATION

KW - ASSOCIATION CONSORTIUM

KW - MAMMALIAN-CELLS

U2 - 10.1158/1055-9965.EPI-09-0187

DO - 10.1158/1055-9965.EPI-09-0187

M1 - Article

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 9

VL - 18

SP - 2476

EP - 2484

ER -