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dc.contributor.advisorAbraham, Ivoen
dc.contributor.authorOh, Yeum Mok
dc.creatorOh, Yeum Moken
dc.date.accessioned2017-09-28T22:10:23Z
dc.date.available2017-09-28T22:10:23Z
dc.date.issued2017
dc.identifier.urihttp://hdl.handle.net/10150/625685
dc.description.abstractBackground: The relevant risks associated with BRCA1 and BRCA2 mutation in breast and ovarian cancer have been well studied. BRCA mutations have also been found to be associated with other cancers, including colorectal cancer, but with conflicting results. Aims: We performed a systematic review and meta-analysis to identify, characterize, and review published studies evaluating BRCA mutation carriers with colorectal cancer, and to quantify the risk of colorectal cancer overall and in subgroups of BRCA mutation carriers. Methods: Eligible studies were retrieved through systematic review using multiple databases. Unadjusted odds ratios were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type, comparison group, and study design. Results: A total of 18 studies were included in the systematic review, of which 14 were also used in the meta-analysis: seven cohort studies comparing to the general population, five case-control studies, four cohort studies involving pedigree analysis, and two kin-cohort studies. Meta-analysis not differentiating between BRCA1 and BRCA2, revealed a statistically significant increased risk of colorectal cancer in BRCA mutation carriers in a fixed-effects model (OR=1.22, 95%CI=1.01-1.48, p=0.041), but not in a random-effects model (OR=1.20, 95%CI=0.96-1.50, p=0.111). Analyses stratified by study design and comparator found no association between BRCA mutation and colorectal cancer risk. In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR=1.48, 95%CI=1.13-1.94, p=0.005), but not in BRCA2 mutation. Conclusion: Systematic review and meta-analysis point at potential 1.22-fold greater risk of colorectal cancer in BRCA mutation carriers, attributable largely to a 1.48-fold greater risk of colorectal cancer in BRCA1 mutation carriers, regardless of age.
dc.language.isoen_USen
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.titleBRCA1 and BRCA2 Gene Mutations in Colorectal Cancer: A Systematic Review and Meta-Analysisen_US
dc.typetexten
dc.typeElectronic Thesisen
thesis.degree.grantorUniversity of Arizonaen
thesis.degree.levelmastersen
dc.contributor.committeememberAbraham, Ivoen
dc.contributor.committeememberBhattacharjee, Sandipanen
dc.contributor.committeememberSlack, Marionen
dc.contributor.committeememberMcBride, Alien
dc.description.releaseRelease after 28-Jun-2020en
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplinePharmaceutical Sciencesen
thesis.degree.nameM.S.en
html.description.abstractBackground: The relevant risks associated with BRCA1 and BRCA2 mutation in breast and ovarian cancer have been well studied. BRCA mutations have also been found to be associated with other cancers, including colorectal cancer, but with conflicting results. Aims: We performed a systematic review and meta-analysis to identify, characterize, and review published studies evaluating BRCA mutation carriers with colorectal cancer, and to quantify the risk of colorectal cancer overall and in subgroups of BRCA mutation carriers. Methods: Eligible studies were retrieved through systematic review using multiple databases. Unadjusted odds ratios were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type, comparison group, and study design. Results: A total of 18 studies were included in the systematic review, of which 14 were also used in the meta-analysis: seven cohort studies comparing to the general population, five case-control studies, four cohort studies involving pedigree analysis, and two kin-cohort studies. Meta-analysis not differentiating between BRCA1 and BRCA2, revealed a statistically significant increased risk of colorectal cancer in BRCA mutation carriers in a fixed-effects model (OR=1.22, 95%CI=1.01-1.48, p=0.041), but not in a random-effects model (OR=1.20, 95%CI=0.96-1.50, p=0.111). Analyses stratified by study design and comparator found no association between BRCA mutation and colorectal cancer risk. In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR=1.48, 95%CI=1.13-1.94, p=0.005), but not in BRCA2 mutation. Conclusion: Systematic review and meta-analysis point at potential 1.22-fold greater risk of colorectal cancer in BRCA mutation carriers, attributable largely to a 1.48-fold greater risk of colorectal cancer in BRCA1 mutation carriers, regardless of age.


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