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dc.contributor.authorJung, Su Yon
dc.contributor.authorRohan, Thomas
dc.contributor.authorStrickler, Howard
dc.contributor.authorBea, Jennifer
dc.contributor.authorZhang, Zuo-Feng
dc.contributor.authorHo, Gloria
dc.contributor.authorCrandall, Carolyn
dc.date.accessioned2017-11-03T21:50:58Z
dc.date.available2017-11-03T21:50:58Z
dc.date.issued2017-10-12
dc.identifier.citationGenetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk 2017, 12 (10):e0186296 PLOS ONEen
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0186296
dc.identifier.urihttp://hdl.handle.net/10150/625969
dc.description.abstractGenetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance) on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants) had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.
dc.language.isoenen
dc.publisherPUBLIC LIBRARY SCIENCEen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0186296en
dc.rights© 2017 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleGenetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risken
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Canc Ctr, Med & Nutr Scien
dc.identifier.journalPLOS ONEen
dc.description.noteOpen access journal.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-09-11T23:55:01Z
html.description.abstractGenetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance) on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants) had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.


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© 2017 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
Except where otherwise noted, this item's license is described as © 2017 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.