IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0321967.html
   My bibliography  Save this article

A genome-wide SNP-SNP interaction analysis exploring novel interacting loci associated with the risk of recurrence in colorectal cancer

Author

Listed:
  • Aaron A Curtis
  • Yajun Yu
  • Megan Carey
  • Yildiz E Yilmaz
  • Sevtap Savas

Abstract

Background: Genetic factors can influence and predict patient outcomes. The association of interactions of germline SNPs with patient outcomes is an understudied area of prognostic research. In this study, we applied the first genome-wide SNP-SNP interaction analysis in relation to colorectal cancer outcomes. Objectives: Our objective was to explore interacting SNP loci at the genome-wide level that predict the risk of local or distant recurrence (RMFS) in a cohort of stage I-III colorectal cancer patients from the Canadian province of Newfoundland and Labrador. Methods: The patient cohort consisted of 430 unrelated Caucasian patients. Genetic and medical data was collected previously and the genetic data consisted of a total of 384,415 genotyped SNPs. The PLINK epistasis function was utilized to examine pairwise SNP interactions. Select interactions were assessed by multivariable Cox-regression models, adjusting for established clinical covariates. Genomic regions identified were explored for additional interactions. Published databases were utilized to retrieve biological information about the loci identified. Results: After Bonferroni correction for multiple testing, no interaction remained significant. We present the top 20 interactions. The interaction p-values ranged from p = 1.37E-8 to p = 2.14E-9 in this set. Interactions were also tested by multivariable Cox regression models including established clinical covariates. Many of the SNPs were intronic and some of them were functional (e.g., expression quantitative expression loci). Analysis of the other SNPs in the same genomic regions as the interacting SNPs led to the identification of three additional interaction models. Conclusions: We present the results of the first genome-wide SNP-SNP interaction analysis in colorectal cancer outcomes. While no SNP-SNP interaction remained significant after correction for multiple testing, our methodology emphasizes the additional knowledge that can be obtained using interaction analyses while studying prognostic markers.

Suggested Citation

  • Aaron A Curtis & Yajun Yu & Megan Carey & Yildiz E Yilmaz & Sevtap Savas, 2025. "A genome-wide SNP-SNP interaction analysis exploring novel interacting loci associated with the risk of recurrence in colorectal cancer," PLOS ONE, Public Library of Science, vol. 20(6), pages 1-14, June.
    • Handle: RePEc:plo:pone00:0321967
    DOI: 10.1371/journal.pone.0321967
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0321967
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0321967&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0321967?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Fredrick R. Schumacher & Stephanie L. Schmit & Shuo Jiao & Christopher K. Edlund & Hansong Wang & Ben Zhang & Li Hsu & Shu-Chen Huang & Christopher P. Fischer & John F. Harju & Gregory E. Idos & Flavi, 2015. "Genome-wide association study of colorectal cancer identifies six new susceptibility loci," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Rikifumi Ohta & Yosuke Tanigawa & Yuta Suzuki & Manolis Kellis & Shinichi Morishita, 2024. "A polygenic score method boosted by non-additive models," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Pingting Ying & Can Chen & Zequn Lu & Shuoni Chen & Ming Zhang & Yimin Cai & Fuwei Zhang & Jinyu Huang & Linyun Fan & Caibo Ning & Yanmin Li & Wenzhuo Wang & Hui Geng & Yizhuo Liu & Wen Tian & Zhiyong, 2023. "Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0321967. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.