SNP-Target Genes Interaction Perturbing the Cancer Risk in the Post-GWAS

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Nov 26

PMID 36428729

Authors

Wenmin Yang

Te Zhang

Xuming Song

Gaochao Dong

Lin Xu

Feng Jiang

Affiliations

Soon will be listed here.

Abstract

Cancer ranks as the second leading cause of death worldwide, and, being a genetic disease, it is highly heritable. Over the past few decades, genome-wide association studies (GWAS) have identified many risk-associated loci harboring hundreds of single nucleotide polymorphisms (SNPs). Some of these cancer-associated SNPs have been revealed as causal, and the functional characterization of the mechanisms underlying the cancer risk association has been illuminated in some instances. In this review, based on the different positions of SNPs and their modes of action, we discuss the mechanisms underlying how SNPs regulate the expression of target genes to consequently affect tumorigenesis and the development of cancer.

Citing Articles

The Association Between IL-8 Gene Polymorphisms and the Risk of Several Types of Cancer, Especially in Gastric Cancer.

Xu B, Yan Y Cancer Rep (Hoboken). 2025; 8(1):e70103.

PMID: 39821721 PMC: 11740087. DOI: 10.1002/cnr2.70103.

A computational and structural approach to identify malignant non-synonymous FOXM1 single nucleotide polymorphisms in triple-negative breast cancer.

Chatterjee P, Banerjee S Sci Rep. 2025; 15(1):964.

PMID: 39762471 PMC: 11704209. DOI: 10.1038/s41598-024-85100-w.

Analysis of Polymorphisms on the Clinicopathologic Characteristics of Asian Patients with Hepatocellular Carcinoma.

Chien Y, Lee H, Chiang W, Bai L, Hung Y, Chen S J Cancer. 2024; 15(16):5183-5190.

PMID: 39247597 PMC: 11375538. DOI: 10.7150/jca.98520.

Variation to biology: optimizing functional analysis of cancer risk variants.

Nelson S, Carrick D, Daee D, Fingerman I, Gillanders E J Natl Cancer Inst. 2024; 116(12):1882-1889.

PMID: 39052872 PMC: 11630534. DOI: 10.1093/jnci/djae173.

The landscape of 8q24 cytoband in gastric cancer (Review).

Larios-Serrato V, Valdez-Salazar H, Ruiz-Tachiquin M Oncol Lett. 2024; 27(4):179.

PMID: 38464340 PMC: 10921260. DOI: 10.3892/ol.2024.14311.

References

Meng Q, Wu S, Wang Y, Xu J, Sun H, Lu R . Promoter Polymorphism rs2333227 Enhances Malignant Phenotypes of Colorectal Cancer by Altering the Binding Affinity of AP-2α. Cancer Res. 2018; 78(10):2760-2769. PMC: 6084780. DOI: 10.1158/0008-5472.CAN-17-2538. View

Yang L, Kartsonaki C, Yao P, de Martel C, Plummer M, Chapman D . The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study. Lancet Public Health. 2021; 6(12):e888-e896. PMC: 8646857. DOI: 10.1016/S2468-2667(21)00164-X. View

Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui S, Kar S . Association analysis identifies 65 new breast cancer risk loci. Nature. 2017; 551(7678):92-94. PMC: 5798588. DOI: 10.1038/nature24284. View

Schodel J, Bardella C, Sciesielski L, Brown J, Pugh C, Buckle V . Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression. Nat Genet. 2012; 44(4):420-5, S1-2. PMC: 3378637. DOI: 10.1038/ng.2204. View

Tian J, Lou J, Cai Y, Rao M, Lu Z, Zhu Y . Risk SNP-Mediated Enhancer-Promoter Interaction Drives Colorectal Cancer through Both and . Cancer Res. 2020; 80(9):1804-1818. DOI: 10.1158/0008-5472.CAN-19-2389. View

Haberle V, Stark A . Eukaryotic core promoters and the functional basis of transcription initiation. Nat Rev Mol Cell Biol. 2018; 19(10):621-637. PMC: 6205604. DOI: 10.1038/s41580-018-0028-8. View

Yusufzai T, Tagami H, Nakatani Y, Felsenfeld G . CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell. 2004; 13(2):291-8. DOI: 10.1016/s1097-2765(04)00029-2. View

Garcia-Closas M, Couch F, Lindstrom S, Michailidou K, Schmidt M, Brook M . Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet. 2013; 45(4):392-8, 398e1-2. PMC: 3771695. DOI: 10.1038/ng.2561. View

Bardou M, Barkun A, Martel M . Obesity and colorectal cancer. Gut. 2013; 62(6):933-47. DOI: 10.1136/gutjnl-2013-304701. View

10.

Tian J, Chang J, Gong J, Lou J, Fu M, Li J . Systematic Functional Interrogation of Genes in GWAS Loci Identified ATF1 as a Key Driver in Colorectal Cancer Modulated by a Promoter-Enhancer Interaction. Am J Hum Genet. 2019; 105(1):29-47. PMC: 6612518. DOI: 10.1016/j.ajhg.2019.05.004. View

11.

Shibata T, Lieblong B, Sasagawa T, Nakagawa M . The promise of combining cancer vaccine and checkpoint blockade for treating HPV-related cancer. Cancer Treat Rev. 2019; 78:8-16. PMC: 6710123. DOI: 10.1016/j.ctrv.2019.07.001. View

12.

Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z . A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet. 2011; 43(8):792-6. DOI: 10.1038/ng.875. View

13.

Enciso-Mora V, Hosking F, Di Stefano A, Zelenika D, Shete S, Broderick P . Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222. Br J Cancer. 2013; 108(10):2178-85. PMC: 3670481. DOI: 10.1038/bjc.2013.155. View

14.

Ward L, Kellis M . Interpreting noncoding genetic variation in complex traits and human disease. Nat Biotechnol. 2012; 30(11):1095-106. PMC: 3703467. DOI: 10.1038/nbt.2422. View

15.

Murray P, Young L . An etiological role for the Epstein-Barr virus in the pathogenesis of classical Hodgkin lymphoma. Blood. 2019; 134(7):591-596. DOI: 10.1182/blood.2019000568. View

16.

Schottenfeld D, Beebe-Dimmer J, Buffler P, Omenn G . Current perspective on the global and United States cancer burden attributable to lifestyle and environmental risk factors. Annu Rev Public Health. 2013; 34:97-117. DOI: 10.1146/annurev-publhealth-031912-114350. View

17.

Raderer M, Kiesewetter B, Ferreri A . Clinicopathologic characteristics and treatment of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). CA Cancer J Clin. 2016; 66(2):153-71. DOI: 10.3322/caac.21330. View

18.

Yan J, Chen S, Local A, Liu T, Qiu Y, Dorighi K . Histone H3 lysine 4 monomethylation modulates long-range chromatin interactions at enhancers. Cell Res. 2018; 28(2):204-220. PMC: 5799818. DOI: 10.1038/cr.2018.1. View

19.

Ng P, Henikoff S . SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003; 31(13):3812-4. PMC: 168916. DOI: 10.1093/nar/gkg509. View

20.

Wang H, Yang B, Cai X, Cheng X, Shen N, Liu L . Hepatocellular carcinoma risk variant modulates lncRNA HLA-DQB1-AS1 expression via a long-range enhancer-promoter interaction. Carcinogenesis. 2021; 42(11):1347-1356. DOI: 10.1093/carcin/bgab095. View