Genetic Determinants of Cancer Susceptibility

Angel, Joe M.; DiGiovanni, John

doi:10.1016/b978-0-12-801238-3.65251-0

Cited by 5 publications

(5 citation statements)

References 337 publications

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“…Analysis of genetic crosses between resistant and susceptible strains suggests the involvement of multiple genes that contribute to AOM susceptibility (Ruivenkamp et al 2003;Meunier et al 2010Meunier et al , 2011Meunier et al , 2013Eversley et al 2012;Liu et al 2012;Angel and DiGiovanni 2018), consistent with GWAS in humans (Tomlinson et al 2007(Tomlinson et al , 2008Zanke et al 2007;COGENT Study et al 2008;Tenesa et al 2008;Tenesa and Dunlop 2009;Theodoratou et al 2012;Schumacher et al 2015;Montazeri et al 2016;Tanikawa et al 2018;Bien et al 2019;Lu et al 2019). Crosses between susceptible and resistant strains manifest a resistant phenotype in both F1 mice and N2 progeny generated by backcrossing F1 mice to their resistant parental strain.…”

Section: Discussionmentioning

confidence: 53%

“…Previous mapping studies have reported 24 modifier alleles that contribute to the susceptibility of DMH or AOM-induced CRC (Moen et al 1992(Moen et al , 1996Jacoby et al 1994;van Wezel et al 1999;Angel et al 2000;Ruivenkamp et al 2003; Meunier et al 2010Meunier et al , 2011Meunier et al , 2013Eversley et al 2012;Liu et al 2012). Of the 24 modifiers, Colon cancer susceptibility 2 (Ccs2) overlaps with Susceptibility to colon cancer 7 (Scc7) on Chromosome (Chr) 3, while the remaining modifiers are distributed across 13 different chromosomes (Angel and DiGiovanni 2018). To extend the number, and to narrow the location of CRC modifiers, haplotype association mapping (HAM) (McClurg et al 2006(McClurg et al , 2007 and tree-based association mapping (Pan et al 2009) were performed using dense SNP maps and AOM susceptibility data from the inbred strain panel.…”

Section: Multiple Alleles Contribute To Aom-induced Carcinogenesis Sumentioning

confidence: 99%

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A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model

et al. 2020

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The azoxymethane model of colorectal cancer (CRC) was used to gain insights into the genetic heterogeneity of nonfamilial CRC. We observed significant differences in susceptibility parameters across 40 mouse inbred strains, with 6 new and 18 of 24 previously identified mouse CRC modifier alleles detected using genome-wide association analysis. Tumor incidence varied in F1 as well as intercrosses and backcrosses between resistant and susceptible strains. Analysis of inheritance patterns indicates that resistance to CRC development is inherited as a dominant characteristic genome-wide, and that susceptibility appears to occur in individuals lacking a large-effect, or sufficient numbers of small-effect, polygenic resistance alleles. Our results suggest a new polygenic model for inheritance of nonfamilial CRC, and that genetic studies in humans aimed at identifying individuals with elevated susceptibility should be pursued through the lens of absence of dominant resistance alleles rather than for the presence of susceptibility alleles.

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Section: Discussionmentioning

confidence: 53%

Section: Multiple Alleles Contribute To Aom-induced Carcinogenesis Sumentioning

confidence: 99%

A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model

et al. 2020

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“…CYP1B1 is expressed in the endoplasmic reticulum of extrahepatic organs. 77 , 78 Tumor cells have shown to express high levels of this enzyme, and this is associated with tumor progression. 38 CYP1B1 does not metabolize taxanes, but it binds to them, thereby reducing cellular availability.…”

Section: Discussionmentioning

confidence: 99%

“…CYP1B1 encodes for a cytochrome enzyme that, unlike others, is not expressed in the human liver and therefore not involved in hepatic metabolism. CYP1B1 is expressed in the endoplasmic reticulum of extrahepatic organs 77,78 . Tumor cells have shown to express high levels of this enzyme, and this is associated with tumor progression 38 .…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics of taxane‐induced neurotoxicity in breast cancer: Systematic review and meta‐analysis

Guijosa

Freyria

Espinosa-Fernandez

et al. 2022

Clinical Translational Sci

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Taxane‐based chemotherapy regimens are used as first‐line treatment for breast cancer. Neurotoxicity, mainly taxane‐induced peripheral neuropathy (TIPN), remains the most important dose‐limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random‐effects gene meta‐analyses and examined interstudy heterogeneity with meta‐regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single‐nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta‐analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1‐rs2032582, ABCB1‐rs3213619, BCL6/‐rs1903216, /CAND1‐rs17781082, CYP1B1‐rs1056836, CYP2C8‐rs10509681, CYP2C8‐rs11572080, EPHA5‐rs7349683, EPHA6‐rs301927, FZD3‐rs7001034, GSTP1‐rs1138272, TUBB2A‐rs9501929, and XKR4‐rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta‐analysis. In conclusion, through systematic review and meta‐analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.

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“…Elevated CYP1B1 expression in prostate tumors and particularly in poor responders ( Figure 3 and Figure 4 ) underscores a high potential for drug resistance. Pathways identified in enrichment and network analysis of CYP1B1 ( Figure 5 and Table S3 ) align with its role in activating pathways associated with drug resistance in prostate cancer [ 24 ]. Unconventional steroid metabolism pathways driven by CYP1B1 are implicated in prostate cancer malignancy [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Signatures for Distinguishing Chemo-Sensitive from Chemo-Resistant Responders in Prostate Cancer Patients

Gumenku,

Sekhoacha,

Abrahams

et al. 2024

CIMB

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Prostate cancer remains a significant public health concern in sub-Saharan Africa, particularly impacting South Africa with high mortality rates. Despite many years of extensive research and significant financial expenditure, there has yet to be a definitive solution to prostate cancer. It is not just individuals who vary in their response to treatment, but even different nodules within the same tumor exhibit unique transcriptome patterns. These distinctions extend beyond mere differences in gene expression levels to encompass the control and networking of individual genes. Escalating chemotherapy resistance in prostate cancer patients has prompted increased research into its underlying mechanisms. The heterogeneous nature of transcriptomic organization among men makes the pursuit of universal biomarkers and one-size-fits-all treatments impractical. This study delves into the expression of drug resistance-associated genes, ABCB1 and CYP1B1, in cancer cells. Employing bioinformatics, we explored the molecular pathways and cascades linked to drug resistance following upregulation of these genes. Samples were obtained from archived prostate cancer patient specimens through pre-treatment biopsies of two categories: good vs. poor responders, with cDNAs synthesized from isolated RNAs subjected to qPCR analysis. The results revealed increased ABCB1 and CYP1B1 expression in tumor samples of the poor responders. Gene enrichment and network analysis associated ABCB1 with ABC transporters and LncRNA-mediated therapeutic resistance (WP3672), while CYP1B1 was linked to ovarian steroidogenesis, tryptophan metabolism, steroid hormone biosynthesis, benzo(a)pyrene metabolism, the sulindac metabolic pathway, and the estrogen receptor pathway, which are associated with drug resistance. Both ABCB1 and CYP1B1 correlated with microRNAs in cancer and the Nuclear Receptors Meta-Pathway. STRING analysis predicted protein–protein interactions of ABCB1 and CYP1B1 with Glutathione S-transferase Pi, Catechol O-methyltransferase, UDP-glucuronosyltransferase 1-6, Leucine-rich Transmembrane and O-methyltransferase (LRTOMT), and Epoxide hydrolase 1, with scores of 0.973, 0.971, 0.966, 0.966, and 0.966, respectively. Furthermore, molecular docking analysis of the chemotherapy drug, docetaxel, with CYP1B1 and ABCB1 revealed robust molecular interactions, with binding energies of −20.37 and −15.25 Kcal/mol, respectively. These findings underscore the susceptibility of cancer patients to drug resistance due to increased ABCB1 and CYP1B1 expression in tumor samples from patients in the poor-responders category that affects associated molecular pathways. The potent molecular interactions of ABCB1 and CYP1B1 with docetaxel further emphasize the potential basis for chemotherapy resistance.

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Genetic Determinants of Cancer Susceptibility

Cited by 5 publications

References 337 publications

A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model

A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model

Pharmacogenetics of taxane‐induced neurotoxicity in breast cancer: Systematic review and meta‐analysis

Genetic Signatures for Distinguishing Chemo-Sensitive from Chemo-Resistant Responders in Prostate Cancer Patients

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