Colorectal cancer-susceptibility single-nucleotide polymorphisms in Korean population

Authors

  • Sung Noh Hong,

    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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    • Sung Noh Hong and Changho Park contributed equally to this work as first author.
  • Changho Park,

    1. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
    2. Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea
    3. Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea
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    • Sung Noh Hong and Changho Park contributed equally to this work as first author.
  • Jong-il Kim,

    1. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
    2. Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea
    3. Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea
    4. Psoma Therapeutics Inc., Seoul, Korea
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  • Duk-Hwan Kim,

    1. Department of Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Hee Cheol Kim,

    1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Dong Kyung Chang,

    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Poong-Lyul Rhee,

    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Jae J. Kim,

    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Jong Chul Rhee,

    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Hee Jung Son,

    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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    • Young-Ho Kim and Hee Jung Son contributed equally to this work as corresponding author.
  • Young-Ho Kim

    Corresponding author
    1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    • Correspondence

      Young-Ho Kim, Department of Medicine, Samsung Medical Center (135-710), Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 135-710, Korea. Email: younghokim@skku.edu

      Hee Jung Son, Department of Medicine, Samsung Medical Center (135-710), Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 135-710, Korea. Email: hjls.son@samsung.com

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    • Young-Ho Kim and Hee Jung Son contributed equally to this work as corresponding author.

  • Potential conflicts of interest: There are no potential conflicts of interest for each of the authors.

Abstract

Background and Aim

Considering the significant racial and ethnic diversity in genetic variation, it is unclear whether the genome-wide association studies-identified colorectal cancer (CRC)-susceptibility single-nucleotide polymorphisms (SNPs) discovered in European populations are also relevant to the Korean population. However, studies on CRC-susceptibility SNPs in Koreans are limited.

Methods

To investigate the racial and ethnic diversity of CRC-susceptibility genetic variants, we genotyped for the established European CRC-susceptibility SNPs in 198 CRC cases and 329 controls in Korea. To identify novel genetic variants using genome-wide screening in Korea, Illumina HumanHap 370K/610K BeadChips were performed on 105 CRC patients, and candidate CRC-susceptibility SNPs were selected. Subsequently, genotyping for replication was done in 189 CRC cases and 190 controls.

Results

Among the European CRC-susceptibility SNPs, rs4939827 in SMAD7 was associated with a significant decreased risk of Korean CRC (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 0.67 [95% CI, 0.47–0.95]; dominant model, 0.59 [95% CI, 0.39–0.91]). rs4779584 and rs10795668 were associated with CRC risk in females and males, respectively. Among candidate CRC-susceptibility SNPs selected from genome-wide screening, novel SNP, rs17051076, was found to be associated with a significantly increased risk of microsatellite instability-high CRC (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 4.25 [95% CI, 1.51–11.98]; dominant model, 3.52 [95% CI, 1.13–10.94]) in the replication study.

Conclusions

rs4939827, rs4779584, and rs10795668 may contribute to the risk of CRC in the Korean population as well as in European populations. Novel rs17051076 could be associated with microsatellite instability-high CRC in Koreans. These associations support the ethnic diversity of CRC-susceptibility SNPs and should be taken into account in large-scale studies.

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