. 2017 Oct; 17(11):692-704.
doi: 10.1038/nrc.2017.82.

Genome-wide association studies of cancer: current insights and future perspectives

Amit Sud 1 Ben Kinnersley 1 Richard S Houlston 1 
  • PMID: 29026206
  •     74 citations


Genome-wide association studies (GWAS) provide an agnostic approach for investigating the genetic basis of complex diseases. In oncology, GWAS of nearly all common malignancies have been performed, and over 450 genetic variants associated with increased risks have been identified. As well as revealing novel pathways important in carcinogenesis, these studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers. The clinical application of GWAS is starting to provide opportunities for drug discovery and repositioning as well as for cancer prevention. However, deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS.

Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci.
Karim Labreche, Ben Kinnersley, +10 authors, Marc Sanson.
Acta Neuropathol, 2018 Feb 21; 135(5). PMID: 29460007    Free PMC article.
Looking back and looking forward.
Maximilian Muenke, Suzanne Hart.
Mol Genet Genomic Med, 2018 Feb 23; 6(1). PMID: 29471589    Free PMC article.
Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities.
Shyh-Han Tan, Gyorgy Petrovics, Shiv Srivastava.
Int J Mol Sci, 2018 Apr 25; 19(4). PMID: 29690565    Free PMC article.
Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.
Elizabeth B Claus, Alex J Cornish, +20 authors, Joseph L Wiemels.
Neuro Oncol, 2018 May 16; 20(11). PMID: 29762745    Free PMC article.
Beginning at the ends: telomeres and human disease.
Sharon A Savage.
F1000Res, 2018 May 18; 7. PMID: 29770205    Free PMC article.
Highly Cited. Review.
Impact of sex, body mass index and initial pathologic diagnosis age on the incidence and prognosis of different types of cancer.
Xuan Huang, Chuanjun Shu, Li Chen, Bing Yao.
Oncol Rep, 2018 Jun 30; 40(3). PMID: 29956810    Free PMC article.
Familial risks of acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms.
Amit Sud, Subhayan Chattopadhyay, +4 authors, Kari Hemminki.
Blood, 2018 Jul 12; 132(9). PMID: 29991558    Free PMC article.
Fine mapping of 2q35 high-risk neuroblastoma locus reveals independent functional risk variants and suggests full-length BARD1 as tumor-suppressor.
Flora Cimmino, Marianna Avitabile, +11 authors, Mario Capasso.
Int J Cancer, 2018 Aug 23; 143(11). PMID: 30132831    Free PMC article.
Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.
Amit Sud, Hauke Thomsen, +26 authors, Richard S Houlston.
Blood, 2018 Sep 09; 132(19). PMID: 30194254    Free PMC article.
Analysis of Racial/Ethnic Representation in Select Basic and Applied Cancer Research Studies.
Santiago Guerrero, Andrés López-Cortés, +7 authors, César Paz-Y-Miño.
Sci Rep, 2018 Sep 20; 8(1). PMID: 30228363    Free PMC article.
Leveraging Human Genetics to Guide Cancer Drug Development.
Ben Kinnersley, Amit Sud, +4 authors, Richard S Houlston.
JCO Clin Cancer Inform, 2019 Jan 18; 2. PMID: 30652614    Free PMC article.
Mendelian randomisation: A powerful and inexpensive method for identifying and excluding non-genetic risk factors for colorectal cancer.
Alex J Cornish, Ian P M Tomlinson, Richard S Houlston.
Mol Aspects Med, 2019 Feb 03; 69. PMID: 30710596    Free PMC article.
Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis.
Pin Wang, Yunshan Wang, +14 authors, Jian-Hua Mao.
Gut, 2019 Mar 08; 68(11). PMID: 30842212    Free PMC article.
The Need for Multi-Omics Biomarker Signatures in Precision Medicine.
Michael Olivier, Reto Asmis, +2 authors, Laura A Cox.
Int J Mol Sci, 2019 Sep 29; 20(19). PMID: 31561483    Free PMC article.
Joint Transcriptomic Analysis of Lung Cancer and Other Lung Diseases.
Beatriz Andrea Otálora-Otálora, Mauro Florez, +3 authors, Adriana Rojas.
Front Genet, 2019 Dec 24; 10. PMID: 31867044    Free PMC article.
Analysis of 153 115 patients with hematological malignancies refines the spectrum of familial risk.
Amit Sud, Subhayan Chattopadhyay, +4 authors, Kari Hemminki.
Blood, 2019 Aug 10; 134(12). PMID: 31395603    Free PMC article.
A causal mechanism for childhood acute lymphoblastic leukaemia.
Mel Greaves.
Nat Rev Cancer, 2018 May 23; 18(8). PMID: 29784935    Free PMC article.
Highly Cited. Review.
Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function.
Maud Fagny, John Platig, +2 authors, John Quackenbush.
Br J Cancer, 2019 Dec 07; 122(4). PMID: 31806877    Free PMC article.
Cancer genetics, precision prevention and a call to action.
Clare Turnbull, Amit Sud, Richard S Houlston.
Nat Genet, 2018 Aug 31; 50(9). PMID: 30158684    Free PMC article.
Highly Cited. Review.
Trypsin-encoding PRSS1-PRSS2 variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.
Benjamin O Wolthers, Thomas L Frandsen, +22 authors, Ponte di Legno toxicity working group.
Haematologica, 2018 Nov 24; 104(3). PMID: 30467200    Free PMC article.
Discovery of common and rare genetic risk variants for colorectal cancer.
Jeroen R Huyghe, Stephanie A Bien, +196 authors, Ulrike Peters.
Nat Genet, 2018 Dec 05; 51(1). PMID: 30510241    Free PMC article.
Highly Cited.
Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology.
Molly Went, Amit Sud, +52 authors, Richard S Houlston.
Blood Cancer J, 2019 Jan 04; 9(1). PMID: 30602759    Free PMC article.
Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma.
Isabelle Atkins, Ben Kinnersley, +25 authors, Richard S Houlston.
Cancer Res, 2019 Feb 03; 79(8). PMID: 30709929    Free PMC article.
Association analyses identify 31 new risk loci for colorectal cancer susceptibility.
Philip J Law, Maria Timofeeva, +96 authors, Malcolm G Dunlop.
Nat Commun, 2019 May 16; 10(1). PMID: 31089142    Free PMC article.
Highly Cited.
Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival.
Shun Lu, Calogerina Catalano, +9 authors, Asta Försti.
PLoS One, 2019 May 16; 14(5). PMID: 31091244    Free PMC article.
EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis.
Martina S Elias, Sheila C Wright, +14 authors, Sara J Brown.
J Allergy Clin Immunol, 2019 Jun 04; 144(2). PMID: 31158401    Free PMC article.
Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
Helen E Speedy, Renée Beekman, +15 authors, José I Martín-Subero.
Nat Commun, 2019 Aug 11; 10(1). PMID: 31399598    Free PMC article.
Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.
Molly Went, Ben Kinnersley, +26 authors, Richard S Houlston.
Hum Genomics, 2019 Aug 21; 13(1). PMID: 31429796    Free PMC article.
Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?
Davide Angeli, Samanta Salvi, Gianluca Tedaldi.
Int J Mol Sci, 2020 Feb 13; 21(3). PMID: 32046255    Free PMC article.
Allele-specific genome targeting in the development of precision medicine.
Junjiao Wu, Beisha Tang, Yu Tang.
Theranostics, 2020 Mar 21; 10(7). PMID: 32194858    Free PMC article.
Epistatic effect of TLR3 and cGAS-STING-IKKε-TBK1-IFN signaling variants on colorectal cancer risk.
Calogerina Catalano, Miguel Inacio da Silva Filho, +12 authors, Asta Försti.
Cancer Med, 2019 Dec 24; 9(4). PMID: 31869529    Free PMC article.
MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells.
Temesgen D Fufa, Laura L Baxter, +4 authors, William J Pavan.
Epigenetics Chromatin, 2019 Aug 11; 12(1). PMID: 31399133    Free PMC article.
Impact of polymorphisms within genes involved in regulating DNA methylation in patients with metastatic colorectal cancer enrolled in three independent, randomised, open-label clinical trials: a meta-analysis from TRIBE, MAVERICC and FIRE-3.
Alberto Puccini, Fotios Loupakis, +17 authors, Heinz-Josef Lenz.
Eur J Cancer, 2019 Mar 11; 111. PMID: 30852420    Free PMC article.
A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population.
Yanmei Xu, Jing Li, +10 authors, Xiaozhong Wang.
Int J Genomics, 2020 Apr 08; 2020. PMID: 32258092    Free PMC article.
Systematic evaluation of cancer-specific genetic risk score for 11 types of cancer in The Cancer Genome Atlas and Electronic Medical Records and Genomics cohorts.
Zhuqing Shi, Hongjie Yu, +8 authors, Jianfeng Xu.
Cancer Med, 2019 Apr 11; 8(6). PMID: 30968590    Free PMC article.
Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk.
Wenjun Yang, Hongliang Liu, +8 authors, Qingyi Wei.
Cancer Sci, 2019 Apr 12; 110(6). PMID: 30972876    Free PMC article.
Going to extremes: determinants of extraordinary response and survival in patients with cancer.
Flurina A M Saner, Alan Herschtal, +13 authors, David D L Bowtell.
Nat Rev Cancer, 2019 May 12; 19(6). PMID: 31076661    Free PMC article.
Overcoming cancer therapeutic bottleneck by drug repurposing.
Zhe Zhang, Li Zhou, +4 authors, Canhua Huang.
Signal Transduct Target Ther, 2020 Jul 04; 5(1). PMID: 32616710    Free PMC article.
Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.
Yan Dora Zhang, Amber N Hurson, +102 authors, Montserrat Garcia-Closas.
Nat Commun, 2020 Jul 06; 11(1). PMID: 32620889    Free PMC article.
Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.
Ainsley Mike Antao, Apoorvi Tyagi, Kye-Seong Kim, Suresh Ramakrishna.
Cancers (Basel), 2020 Jun 19; 12(6). PMID: 32549302    Free PMC article.
Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.
W Dai, H Liu, +12 authors, Q Wei.
Br J Dermatol, 2020 Jan 20; 183(4). PMID: 31955403    Free PMC article.
Population Differentiation at the PVT1 Gene Locus: Implications for Prostate Cancer.
Gargi Pal, Lia Di, +3 authors, Olorunseun O Ogunwobi.
G3 (Bethesda), 2020 May 03; 10(7). PMID: 32358016    Free PMC article.
Cancer Risk Studies and Priority Areas for Cancer Risk Appraisal in Uganda.
Alfred Jatho, Binh Thang Tran, +2 authors, Noleb Mugume Mugisha.
Ann Glob Health, 2020 Jul 25; 86(1). PMID: 32704483    Free PMC article.
Leveraging Genome and Phenome-Wide Association Studies to Investigate Genetic Risk of Acute Lymphoblastic Leukemia.
Eleanor C Semmes, Jayaram Vijayakrishnan, +3 authors, Kyle M Walsh.
Cancer Epidemiol Biomarkers Prev, 2020 May 30; 29(8). PMID: 32467347    Free PMC article.
The Community Oncology and Academic Medical Center Alliance in the Age of Precision Medicine: Cancer Genetics and Genomics Considerations.
Marilena Melas, Shanmuga Subbiah, +2 authors, Kevin J McDonnell.
J Clin Med, 2020 Jul 10; 9(7). PMID: 32640668    Free PMC article.
Using genetics to decipher the link between type 2 diabetes and cancer: shared aetiology or downstream consequence?
Emma E Vincent, Hanieh Yaghootkar.
Diabetologia, 2020 Jul 25; 63(9). PMID: 32705315    Free PMC article.
Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival.
Wei Dai, Hongliang Liu, +9 authors, Qingyi Wei.
Mol Carcinog, 2020 Apr 02; 59(6). PMID: 32232919    Free PMC article.
Critical Analysis of Genome-Wide Association Studies: Triple Negative Breast Cancer Quae Exempli Causa.
Maria-Ancuta Jurj, Mihail Buse, +4 authors, Ioana Berindan-Neagoe.
Int J Mol Sci, 2020 Aug 23; 21(16). PMID: 32823908    Free PMC article.
Mouse tumor susceptibility genes identify drug combinations for multiple myeloma.
Shuling Zhang, Wendy DuBois, +6 authors, Beverly A Mock.
J Cancer Metastasis Treat, 2020 Sep 15; 6. PMID: 32923678    Free PMC article.
krCRISPR: an easy and efficient strategy for generating conditional knockout of essential genes in cells.
Bei Wang, Zishi Wang, +5 authors, Yongming Wang.
J Biol Eng, 2019 May 03; 13. PMID: 31049076    Free PMC article.
Population Levels Assessment of the Distribution of Disease-Associated Variants With Emphasis on Armenians - A Machine Learning Approach.
Maria Nikoghosyan, Siras Hakobyan, +3 authors, Arsen Arakelyan.
Front Genet, 2019 May 21; 10. PMID: 31105750    Free PMC article.
Familial Risks and Mortality in Second Primary Cancers in Melanoma.
Subhayan Chattopadhyay, Akseli Hemminki, +3 authors, Kari Hemminki.
JNCI Cancer Spectr, 2019 Jul 31; 2(4). PMID: 31360883    Free PMC article.
SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility.
Esmat Abdi, Saeid Latifi-Navid, +4 authors, Farhad Pourfarzi.
Sci Rep, 2020 Oct 09; 10(1). PMID: 33028884    Free PMC article.
Cancer Predisposition Genes in Cancer-Free Families.
Guoqiao Zheng, Calogerina Catalano, +9 authors, Asta Försti.
Cancers (Basel), 2020 Oct 01; 12(10). PMID: 32992489    Free PMC article.
Genomic prediction of relapse in recipients of allogeneic haematopoietic stem cell transplantation.
J Ritari, K Hyvärinen, +9 authors, J Partanen.
Leukemia, 2018 Aug 10; 33(1). PMID: 30089915    Free PMC article.
Moving the needle on colorectal cancer genetics: it takes more than two to TANGO.
Luis G Carvajal-Carmona.
Br J Cancer, 2018 Oct 05; 119(8). PMID: 30283142    Free PMC article.
Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers.
Durray Shahwar, Muhammad Javed Iqbal, +6 authors, Baojun Xu.
Int J Mol Sci, 2019 Apr 27; 20(8). PMID: 31022877    Free PMC article.
Recent Advances in Understanding the Role of Genomic and Epigenomic Factors in Noncommunicable Diseases.
Hossain U Shekhar, Sajib Chakraborty, Kaiissar Mannoor, Altaf H Sarker.
Biomed Res Int, 2019 May 14; 2019. PMID: 31080807    Free PMC article.
Molecular Dynamics Simulations Predict That rSNP Located in the HNF‑1α Gene Promotor Region Linked with MODY3 and Hepatocellular Carcinoma Promotes Stronger Binding of the HNF‑4α Transcription Factor.
Eva Španinger, Uroš Potočnik, Urban Bren.
Biomolecules, 2020 Dec 30; 10(12). PMID: 33371430    Free PMC article.
Case-control analysis identifies shared properties of rare germline variation in cancer predisposing genes.
Mykyta Artomov, Vijai Joseph, +17 authors, Mark J Daly.
Eur J Hum Genet, 2019 Feb 06; 27(5). PMID: 30718883    Free PMC article.
The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia.
Irina A Elcheva, Vladimir S Spiegelman.
Cancers (Basel), 2021 Jan 10; 12(12). PMID: 33419342    Free PMC article.
Systematic evaluation of the effects of genetic variants on PIWI-interacting RNA expression across 33 cancer types.
Junyi Xin, Mulong Du, +7 authors, Meilin Wang.
Nucleic Acids Res, 2020 Dec 18; 49(1). PMID: 33330918    Free PMC article.
8q24.21 Locus: A Paradigm to Link Non-Coding RNAs, Genome Polymorphisms and Cancer.
Claire Wilson, Aditi Kanhere.
Int J Mol Sci, 2021 Jan 28; 22(3). PMID: 33499210    Free PMC article.
Genome-wide association study across pediatric central nervous system tumors implicates shared predisposition and points to 1q25.2 (PAPPA2) and 11p12 (LRRC4C) as novel candidate susceptibility loci.
Jon Foss-Skiftesvik, Christian Munch Hagen, +11 authors, Jonas Bybjerg-Grauholm.
Childs Nerv Syst, 2020 Nov 24; 37(3). PMID: 33226468
Fluorescence Sheds Light on DNA Damage, DNA Repair, and Mutations.
Norah A Owiti, Zachary D Nagel, Bevin P Engelward.
Trends Cancer, 2020 Nov 19; 7(3). PMID: 33203608    Free PMC article.
Genetic cancer predisposition syndromes among older adults.
Yanin Chavarri-Guerra, Thomas P Slavin, Ossian Longoria-Lozano, Jeffrey N Weitzel.
J Geriatr Oncol, 2020 Jan 26; 11(7). PMID: 31980412    Free PMC article.
Pentagalloyl glucose inhibits TNF-α-activated CXCL1/GRO-α expression and induces apoptosis-related genes in triple-negative breast cancer cells.
Patricia Mendonca, Sumaih Alghamdi, Samia Messeha, Karam F A Soliman.
Sci Rep, 2021 Mar 13; 11(1). PMID: 33707603    Free PMC article.
Identification of common predisposing loci to hematopoietic cancers in four dog breeds.
Benoît Hédan, Édouard Cadieu, +8 authors, Catherine André.
PLoS Genet, 2021 Apr 02; 17(4). PMID: 33793571    Free PMC article.
Quantitative methods for metabolomic analyses evaluated in the Children's Health Exposure Analysis Resource (CHEAR).
CHEAR Metabolomics Analysis Team, Matthew Mazzella, +9 authors, Chris Gennings.
J Expo Sci Environ Epidemiol, 2019 Sep 25; 30(1). PMID: 31548623    Free PMC article.
Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival.
Haijiao Wang, Hongliang Liu, +7 authors, Qingyi Wei.
Ann Transl Med, 2021 Apr 13; 9(5). PMID: 33842617    Free PMC article.
Germline Variants That Affect Tumor Progression.
Ajay Chatrath, Aakrosh Ratan, Anindya Dutta.
Trends Genet, 2020 Nov 19; 37(5). PMID: 33203571    Free PMC article.
Crohn's disease-associated ATG16L1 T300A genotype is associated with improved survival in gastric cancer.
Changqing Ma, Chad E Storer, +8 authors, Ta-Chiang Liu.
EBioMedicine, 2021 Apr 28; 67. PMID: 33906066    Free PMC article.
Will polygenic risk scores for cancer ever be clinically useful?
Amit Sud, Clare Turnbull, Richard Houlston.
NPJ Precis Oncol, 2021 May 23; 5(1). PMID: 34021222    Free PMC article.
DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population.
Maria Samara, Maria Papathanassiou, +3 authors, Vassilios Tzortzis.
Curr Oncol, 2021 Jun 03; 28(3). PMID: 34068981    Free PMC article.