TY - JOUR
T1 - Distinct genetic association at the PLCE1 locus with oesophageal squamous cell carcinoma in the South African population
AU - Bye, Hannah
AU - Prescott, Natalie J.
AU - Lewis, Cathryn M.
AU - Matejcic, Marco
AU - Moodley, Loven
AU - Robertson, Barbara
AU - van Rensburg, Christo
AU - Parker, M. Iqbal
AU - Mathew, Christopher G.
N1 - Funding Information:
Association for International Cancer Research (09-0625), the Medical Research Council UK, The Generation Trust, the National Institutes of Health Research Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London to H.B., N.J.P., C.M.L., C.G.M., The South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation, the International Centre for Genetic Engineering and Biotechnology (ICGEB), the South African Medical Research Council and the University of Cape Town to M.I.P.
PY - 2012/11
Y1 - 2012/11
N2 - Oesophageal squamous cell carcinoma (OSCC) has a high prevalence in the Black and Mixed Ancestry populations of South Africa. Recently, three genome-wide association studies in Chinese populations identified five new OSCC susceptibility loci, including variants at PLCE1, C20orf54, PDE4D, RUNX1 and UNC5CL, but their contribution to disease risk in other populations is unknown. In this study, we report testing variants from these five loci for association with OSCC in the South African Black (407 cases and 849 controls) and Mixed Ancestry (257 cases and 860 controls) populations. The RUNX1 variant rs2014300, which reduced risk in the Chinese population, was associated with an increased risk of OSCC in the Mixed Ancestry population [odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.09-1.63, P = 0.0055], and none of the five loci were associated in the Black population. Since PLCE1 variants increased the risk of OSCC in all three Chinese studies, this gene was investigated further by sequencing in 46 Black South Africans. This revealed 48 variants, 10 of which resulted in amino acid substitutions, and much lower linkage disequilibrium across the PLCE1 locus than in the Chinese population. We genotyped five PLCE1 variants in cases and controls, and found association of Arg548Leu (rs17417407) with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93, P = 0.008) in the Black population. These findings indicate several differences in the genetic contribution to OSCC between the South African and Chinese populations that may be related to differences in their genetic architecture.
AB - Oesophageal squamous cell carcinoma (OSCC) has a high prevalence in the Black and Mixed Ancestry populations of South Africa. Recently, three genome-wide association studies in Chinese populations identified five new OSCC susceptibility loci, including variants at PLCE1, C20orf54, PDE4D, RUNX1 and UNC5CL, but their contribution to disease risk in other populations is unknown. In this study, we report testing variants from these five loci for association with OSCC in the South African Black (407 cases and 849 controls) and Mixed Ancestry (257 cases and 860 controls) populations. The RUNX1 variant rs2014300, which reduced risk in the Chinese population, was associated with an increased risk of OSCC in the Mixed Ancestry population [odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.09-1.63, P = 0.0055], and none of the five loci were associated in the Black population. Since PLCE1 variants increased the risk of OSCC in all three Chinese studies, this gene was investigated further by sequencing in 46 Black South Africans. This revealed 48 variants, 10 of which resulted in amino acid substitutions, and much lower linkage disequilibrium across the PLCE1 locus than in the Chinese population. We genotyped five PLCE1 variants in cases and controls, and found association of Arg548Leu (rs17417407) with a reduced risk of OSCC (OR = 0.74, 95% CI = 0.60-0.93, P = 0.008) in the Black population. These findings indicate several differences in the genetic contribution to OSCC between the South African and Chinese populations that may be related to differences in their genetic architecture.
UR - https://www.scopus.com/pages/publications/84868623103
U2 - 10.1093/carcin/bgs262
DO - 10.1093/carcin/bgs262
M3 - Article
C2 - 22865593
AN - SCOPUS:84868623103
SN - 0143-3334
VL - 33
SP - 2155
EP - 2161
JO - Carcinogenesis
JF - Carcinogenesis
IS - 11
ER -