IDEAS home Printed from https://ideas.repec.org/a/gam/jijerp/v14y2017i10p1146-d113512.html
   My bibliography  Save this article

Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival

Author

Listed:
  • Noha Sharafeldin

    (School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada
    Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA)

  • Martha L. Slattery

    (Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA)

  • Qi Liu

    (School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada)

  • Conrado Franco-Villalobos

    (School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada)

  • Bette J. Caan

    (Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94612, USA)

  • John D. Potter

    (Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA
    Centre for Public Health Research, Massey University, P.O. Box 756, Wellington 6140, New Zealand)

  • Yutaka Yasui

    (School of Public Health, University of Alberta, Edmonton, AB T6G 2R3, Canada
    Department of Epidemiology & Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA)

Abstract

Characterization of gene-environment interactions (GEIs) in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11), TLR4 (OR = 2.34, 95% CI: 1.38, 3.98), and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78) with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72), TLR4 (OR = 2.10, 95% CI: 1.22, 3.60) and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46) with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92) and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81) with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75) with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73), TLR2 (HR = 9.06, 95% CI: 1.14, 72.11), EGR2 (HR = 2.45, 95% CI: 1.42, 4.22), and EGFR (HR = 6.33, 95% CI: 1.95, 20.54) with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.

Suggested Citation

  • Noha Sharafeldin & Martha L. Slattery & Qi Liu & Conrado Franco-Villalobos & Bette J. Caan & John D. Potter & Yutaka Yasui, 2017. "Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival," IJERPH, MDPI, vol. 14(10), pages 1-15, September.
  • Handle: RePEc:gam:jijerp:v:14:y:2017:i:10:p:1146-:d:113512
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/1660-4601/14/10/1146/pdf
    Download Restriction: no

    File URL: https://www.mdpi.com/1660-4601/14/10/1146/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. James Y. Dai & Charles Kooperberg & Michael Leblanc & Ross L. Prentice, 2012. "Two-stage testing procedures with independent filtering for genome-wide gene-environment interaction," Biometrika, Biometrika Trust, vol. 99(4), pages 929-944.
    2. Richard C. Grandison & Matthew D. W. Piper & Linda Partridge, 2009. "Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila," Nature, Nature, vol. 462(7276), pages 1061-1064, December.
    3. Teri A. Manolio & Francis S. Collins & Nancy J. Cox & David B. Goldstein & Lucia A. Hindorff & David J. Hunter & Mark I. McCarthy & Erin M. Ramos & Lon R. Cardon & Aravinda Chakravarti & Judy H. Cho &, 2009. "Finding the missing heritability of complex diseases," Nature, Nature, vol. 461(7265), pages 747-753, October.
    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. Jennifer A. Smith & Wei Zhao & Kalyn Yasutake & Carmella August & Scott M. Ratliff & Jessica D. Faul & Eric Boerwinkle & Aravinda Chakravarti & Ana V. Diez Roux & Yan Gao & Michael E. Griswold & Gerar, 2017. "Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies," IJERPH, MDPI, vol. 14(12), pages 1-18, December.
    2. Kevin R Thornton & Andrew J Foran & Anthony D Long, 2013. "Properties and Modeling of GWAS when Complex Disease Risk Is Due to Non-Complementing, Deleterious Mutations in Genes of Large Effect," PLOS Genetics, Public Library of Science, vol. 9(2), pages 1-14, February.
    3. Ruixue Fan & Shaw-Hwa Lo, 2013. "A Robust Model-free Approach for Rare Variants Association Studies Incorporating Gene-Gene and Gene-Environmental Interactions," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-14, December.
    4. Zhongshang Yuan & Hong Liu & Xiaoshuai Zhang & Fangyu Li & Jinghua Zhao & Furen Zhang & Fuzhong Xue, 2013. "From Interaction to Co-Association —A Fisher r-To-z Transformation-Based Simple Statistic for Real World Genome-Wide Association Study," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-8, July.
    5. Chang Lu & Jan Zaucha & Rihab Gam & Hai Fang & Smithers & Matt E. Oates & Miguel Bernabe-Rubio & James Williams & Natalie Zelenka & Arun Prasad Pandurangan & Himani Tandon & Hashem Shihab & Raju Kalai, 2023. "Hypothesis-free phenotype prediction within a genetics-first framework," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Ian Barnett & Rajarshi Mukherjee & Xihong Lin, 2017. "The Generalized Higher Criticism for Testing SNP-Set Effects in Genetic Association Studies," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 112(517), pages 64-76, January.
    7. Colin D Steer & Patrick Bolton & Jean Golding, 2015. "Preconception and Prenatal Environmental Factors Associated with Communication Impairments in 9 Year Old Children Using an Exposome-Wide Approach," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-26, March.
    8. Ziyun Wu & Shao Quan Liu & Dejian Huang, 2013. "Dietary Restriction Depends on Nutrient Composition to Extend Chronological Lifespan in Budding Yeast Saccharomyces cerevisiae," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-13, May.
    9. Bingxin Zhao & Fei Zou, 2022. "On polygenic risk scores for complex traits prediction," Biometrics, The International Biometric Society, vol. 78(2), pages 499-511, June.
    10. von Stumm, Sophie & Kandaswamy, Radhika & Maxwell, Jessye, 2023. "Gene-environment interplay in early life cognitive development," Intelligence, Elsevier, vol. 98(C).
    11. Jaleal S Sanjak & Anthony D Long & Kevin R Thornton, 2017. "A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets," PLOS Genetics, Public Library of Science, vol. 13(1), pages 1-30, January.
    12. Ai-Ru Hsieh & Dao-Peng Chen & Amrita Sengupta Chattopadhyay & Ying-Ju Li & Chien-Ching Chang & Cathy S J Fann, 2017. "A non-threshold region-specific method for detecting rare variants in complex diseases," PLOS ONE, Public Library of Science, vol. 12(11), pages 1-16, November.
    13. Diana Chang & Alon Keinan, 2012. "Predicting Signatures of “Synthetic Associations” and “Natural Associations” from Empirical Patterns of Human Genetic Variation," PLOS Computational Biology, Public Library of Science, vol. 8(7), pages 1-9, July.
    14. Thomas W Winkler & Anne E Justice & L Adrienne Cupples & Florian Kronenberg & Zoltán Kutalik & Iris M Heid & the GIANT consortium, 2017. "Approaches to detect genetic effects that differ between two strata in genome-wide meta-analyses: Recommendations based on a systematic evaluation," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-23, July.
    15. Ziwei Dai & Weiyan Zheng & Jason W. Locasale, 2022. "Amino acid variability, tradeoffs and optimality in human diet," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    16. Andrew K MacLeod & Gail Davies & Antony Payton & Albert Tenesa & Sarah E Harris & David Liewald & Xiayi Ke & Michelle Luciano & Lorna M Lopez & Alan J Gow & Janie Corley & Paul Redmond & Geraldine McN, 2012. "Genetic Copy Number Variation and General Cognitive Ability," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-9, December.
    17. Zhuoran Xu & Quan Li & Luigi Marchionni & Kai Wang, 2023. "PhenoSV: interpretable phenotype-aware model for the prioritization of genes affected by structural variants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Guo, Fangqi & Harris, Kathleen Mullan & Boardman, Jason D. & Robinette, Jennifer W., 2022. "Does crime trigger genetic risk for type 2 diabetes in young adults? A G x E interaction study using national data," Social Science & Medicine, Elsevier, vol. 313(C).
    19. Surina Singh & Ananyo Choudhury & Scott Hazelhurst & Nigel J. Crowther & Palwendé R. Boua & Hermann Sorgho & Godfred Agongo & Engelbert A. Nonterah & Lisa K. Micklesfield & Shane A. Norris & Isaac Kis, 2023. "Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Gaurav Bhatia & Vikas Bansal & Olivier Harismendy & Nicholas J Schork & Eric J Topol & Kelly Frazer & Vineet Bafna, 2010. "A Covering Method for Detecting Genetic Associations between Rare Variants and Common Phenotypes," PLOS Computational Biology, Public Library of Science, vol. 6(10), pages 1-12, October.

    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:gam:jijerp:v:14:y:2017:i:10:p:1146-:d:113512. 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: MDPI Indexing Manager (email available below). General contact details of provider: https://www.mdpi.com .

    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.