Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population

Wenlong C Chen; Hannah Bye; Marco Matejcic; Ariella Amar; Dhiren Govender; Yee Wen Khew; Victoria Beynon; Robyn Kerr; Elvira Singh; Natalie J Prescott; Cathryn M Lewis; Chantal Babb de Villiers; M Iqbal Parker; Christopher G Mathew

doi:10.1093/carcin/bgz026

Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population

Wenlong C Chen, Hannah Bye, Marco Matejcic, Ariella Amar, Dhiren Govender, Yee Wen Khew, Victoria Beynon, Robyn Kerr, Elvira Singh, Natalie J Prescott, Cathryn M Lewis, Chantal Babb de Villiers, M Iqbal Parker, Christopher G Mathew

University of the Witwatersrand

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Abstract

Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asian and European populations. In this study, we investigated genetic variants from seven OSCC risk loci identified in non-African populations for association with OSCC in the South African Black population. We performed association studies in a total of 1471 cases and 1791 controls from two study sample groups, which included 591 cases and 852 controls from the Western Cape and 880 cases and 939 controls from the Johannesburg region in the Gauteng province. Thereafter, we performed a meta-analysis for 11 variants which had been genotyped in both studies. A single nucleotide polymorphism in the CHEK2 gene, rs1033667, was significantly associated with OSCC [P = 0.002; odds ratio (OR) = 1.176; 95% confidence interval (CI): 1.06-1.30]. However, single nucleotide polymorphisms in the CASP8/ALS2CR12, TMEM173, PLCE1, ALDH2, ATP1B2/TP53 and RUNX1 loci were not associated with the disease (P > 0.05). The lack of association of six of these loci with OSCC in South African populations may reflect different genetic risk factors in non-African and African populations or differences in the genetic architecture of African genomes. The association at CHEK2, a gene with key roles in cell cycle regulation and DNA repair, in an African population provides further support for the contribution of common genetic variants at this locus to the risk of oesophageal cancer.

Original language	English
Article number	bgz026
Pages (from-to)	513-520
Number of pages	8
Journal	Carcinogenesis
Volume	40
Issue number	4
Early online date	12 Feb 2019
DOIs	https://doi.org/10.1093/carcin/bgz026
Publication status	Published - Apr 2019

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Association of genetic variants_CHEN_Accepted07February2019_GOLD AAMAccepted author manuscript, 938 KBLicence: Unspecified

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Chen, W. C., Bye, H., Matejcic, M., Amar, A., Govender, D., Khew, Y. W., Beynon, V., Kerr, R., Singh, E., Prescott, N. J., Lewis, C. M., Babb de Villiers, C., Parker, M. I., & Mathew, C. G. (2019). Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population. Carcinogenesis, 40(4), 513-520. [bgz026]. https://doi.org/10.1093/carcin/bgz026

@article{e4947ea541344e02a70cfff60845a84c,

title = "Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population",

abstract = "Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asian and European populations. In this study, we investigated genetic variants from seven OSCC risk loci identified in non-African populations for association with OSCC in the South African Black population. We performed association studies in a total of 1471 cases and 1791 controls from two study sample groups, which included 591 cases and 852 controls from the Western Cape and 880 cases and 939 controls from the Johannesburg region in the Gauteng province. Thereafter, we performed a meta-analysis for 11 variants which had been genotyped in both studies. A single nucleotide polymorphism in the CHEK2 gene, rs1033667, was significantly associated with OSCC [P = 0.002; odds ratio (OR) = 1.176; 95% confidence interval (CI): 1.06-1.30]. However, single nucleotide polymorphisms in the CASP8/ALS2CR12, TMEM173, PLCE1, ALDH2, ATP1B2/TP53 and RUNX1 loci were not associated with the disease (P > 0.05). The lack of association of six of these loci with OSCC in South African populations may reflect different genetic risk factors in non-African and African populations or differences in the genetic architecture of African genomes. The association at CHEK2, a gene with key roles in cell cycle regulation and DNA repair, in an African population provides further support for the contribution of common genetic variants at this locus to the risk of oesophageal cancer.",

author = "Chen, {Wenlong C} and Hannah Bye and Marco Matejcic and Ariella Amar and Dhiren Govender and Khew, {Yee Wen} and Victoria Beynon and Robyn Kerr and Elvira Singh and Prescott, {Natalie J} and Lewis, {Cathryn M} and {Babb de Villiers}, Chantal and Parker, {M Iqbal} and Mathew, {Christopher G}",

year = "2019",

month = apr,

doi = "10.1093/carcin/bgz026",

language = "English",

volume = "40",

pages = "513--520",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "4",

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Chen, WC, Bye, H, Matejcic, M, Amar, A, Govender, D, Khew, YW, Beynon, V, Kerr, R, Singh, E, Prescott, NJ , Lewis, CM, Babb de Villiers, C, Parker, MI & Mathew, CG 2019, 'Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population', Carcinogenesis, vol. 40, no. 4, bgz026, pp. 513-520. https://doi.org/10.1093/carcin/bgz026

TY - JOUR

T1 - Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population

AU - Chen, Wenlong C

AU - Bye, Hannah

AU - Matejcic, Marco

AU - Amar, Ariella

AU - Govender, Dhiren

AU - Khew, Yee Wen

AU - Beynon, Victoria

AU - Kerr, Robyn

AU - Singh, Elvira

AU - Prescott, Natalie J

AU - Lewis, Cathryn M

AU - Babb de Villiers, Chantal

AU - Parker, M Iqbal

AU - Mathew, Christopher G

PY - 2019/4

Y1 - 2019/4

N2 - Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asian and European populations. In this study, we investigated genetic variants from seven OSCC risk loci identified in non-African populations for association with OSCC in the South African Black population. We performed association studies in a total of 1471 cases and 1791 controls from two study sample groups, which included 591 cases and 852 controls from the Western Cape and 880 cases and 939 controls from the Johannesburg region in the Gauteng province. Thereafter, we performed a meta-analysis for 11 variants which had been genotyped in both studies. A single nucleotide polymorphism in the CHEK2 gene, rs1033667, was significantly associated with OSCC [P = 0.002; odds ratio (OR) = 1.176; 95% confidence interval (CI): 1.06-1.30]. However, single nucleotide polymorphisms in the CASP8/ALS2CR12, TMEM173, PLCE1, ALDH2, ATP1B2/TP53 and RUNX1 loci were not associated with the disease (P > 0.05). The lack of association of six of these loci with OSCC in South African populations may reflect different genetic risk factors in non-African and African populations or differences in the genetic architecture of African genomes. The association at CHEK2, a gene with key roles in cell cycle regulation and DNA repair, in an African population provides further support for the contribution of common genetic variants at this locus to the risk of oesophageal cancer.

AB - Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asian and European populations. In this study, we investigated genetic variants from seven OSCC risk loci identified in non-African populations for association with OSCC in the South African Black population. We performed association studies in a total of 1471 cases and 1791 controls from two study sample groups, which included 591 cases and 852 controls from the Western Cape and 880 cases and 939 controls from the Johannesburg region in the Gauteng province. Thereafter, we performed a meta-analysis for 11 variants which had been genotyped in both studies. A single nucleotide polymorphism in the CHEK2 gene, rs1033667, was significantly associated with OSCC [P = 0.002; odds ratio (OR) = 1.176; 95% confidence interval (CI): 1.06-1.30]. However, single nucleotide polymorphisms in the CASP8/ALS2CR12, TMEM173, PLCE1, ALDH2, ATP1B2/TP53 and RUNX1 loci were not associated with the disease (P > 0.05). The lack of association of six of these loci with OSCC in South African populations may reflect different genetic risk factors in non-African and African populations or differences in the genetic architecture of African genomes. The association at CHEK2, a gene with key roles in cell cycle regulation and DNA repair, in an African population provides further support for the contribution of common genetic variants at this locus to the risk of oesophageal cancer.

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U2 - 10.1093/carcin/bgz026

DO - 10.1093/carcin/bgz026

M3 - Article

C2 - 30753320

SN - 0143-3334

VL - 40

SP - 513

EP - 520

JO - Carcinogenesis

JF - Carcinogenesis

IS - 4

M1 - bgz026

ER -

Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population

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