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Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population

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Abstract

A recently published genome-wide association study (GWAS) in European populations identified several loci at 4q21, 4q23 and 12q24 that were associated with risk of upper aerodigestive tract (UADT) cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we conducted a case–control study in a Chinese population including 2,139 ESCC cases and 2,273 controls to evaluate the associations of six reported single nucleotide polymorphisms (SNPs) (rs1494961, rs1229984, rs1789924, rs971074, rs671 and rs4767364) with risk of ESCC. We found significant association with risk of ESCC for four SNPs, including rs1494961 in HEL308 at 4q21 [odds ratio (OR) = 1.15, 95 % confidence interval (CI) = 1.05–1.26], rs1229984 in ADH1B at 4q23 (OR = 1.24, 95 % CI = 1.13–1.36) and rs1789924 near ADH1C at 4q23 (OR = 1.20, 95 % CI = 1.03-1.39), and rs671 in ALDH2 at 12q24 (OR = 0.83, 95 % CI = 0.75–0.91). Combined analysis of these four SNPs showed a significant allele-dosage effect on ESCC risk for individuals with different number of risk alleles (P trend = 2.23 × 10−11). Compared with individuals with “0–2” risk allele, those carrying “3”, “4” or “5 or more” risk alleles had 1.42-, 1.66-, or 1.76-fold risk of ESCC, respectively. Thus, our findings indicate that rs1494961 at 4q21, rs1229984 and rs1789924 at 4q23, and rs671 at 12q24 may be used as genetic biomarkers for ESCC susceptibility in Chinese population.

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Abbreviations

GWAS:

Genome-wide association study

UADT:

Upper aerodigestive tract

SNPs:

Single nucleotide polymorphisms

OR:

Odds ratio

CI:

Confidence interval

ESCC:

Esophageal squamous cell carcinoma

LD:

Linkage disequilibrium

MAFs:

Minor allele frequencies

HNC:

Head and neck cancer

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Acknowledgments

This work was supported by National Natural Science Foundation of China (Grant numbers: 81001276, 81072380, 81101889); Jiangsu Natural Science Foundation (Grant number: BK2012841); the Key Project of the National Natural Science Foundation of China (Grant number: 81230067); the National Key Basic Research Program Grant (Grant numbers: 2011CB503805, 2013CB910304, 2013CB911400); the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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None declared.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China

    Yong Gao, Yisha He, Jiangbo Du, Chen Zhu, Hongxia Ma, Zhibin Hu, Guangfu Jin & Hongbing Shen

  2. Department of Medical Oncology, The Affiliated Huaian First People’s Hospital of Nanjing Medical University, Huaian, China

    Yong Gao & Xiaofei Chen

  3. Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Jing Xu

  4. Department of Thoracic Surgery, Jiangsu Cancer Hospital, Nanjing, China

    Lin Xu

  5. Department of Thoracic Surgery, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China

    Haiyong Gu

  6. MOE Key Lab of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China

    Yisha He, Jiangbo Du, Chen Zhu, Hongxia Ma, Zhibin Hu, Guangfu Jin & Hongbing Shen

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  1. Yong Gao
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  2. Yisha He
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  3. Jing Xu
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  4. Lin Xu
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  5. Jiangbo Du
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  6. Chen Zhu
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  7. Haiyong Gu
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  8. Hongxia Ma
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  9. Zhibin Hu
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  10. Guangfu Jin
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  11. Xiaofei Chen
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  12. Hongbing Shen
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Corresponding authors

Correspondence to Guangfu Jin, Xiaofei Chen or Hongbing Shen.

Additional information

Y. Gao, Y. He and J. Xu contributed equally to this work.

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Gao, Y., He, Y., Xu, J. et al. Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese population. Hum Genet 132, 649–656 (2013). https://doi.org/10.1007/s00439-013-1276-5

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