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• W1636320324 abstract "Advances in high-throughput genotyping technologies have enabled the efficient systematic screening of single-nucleotide polymorphisms (SNPs) throughout the human genome for disease associations in genome-wide association studies (GWAS). Many human complex diseases have been interrogated by GWAS; these include autoimmune and chronic inflammatory diseases, neurological and neuropsychiatric diseases, cardiovascular diseases and cancers among others. Presently, more than 60 cancer GWAS have been published and numerous novel SNPs and genetic loci were found to be associated with various cancers such as breast, prostate and colorectal cancers. These SNP associations were supported by robust statistical evidence. The GWAS of cancers have so far focused only on SNPs. Other germline genetic variations such as small insertions and deletions (indels), copy number variations (CNVs) and tandem repeat polymorphisms should also be investigated for their associations with cancers in the future.Key Concepts: Cancer is similar to other complex diseases in that it is a consequence of complex interactions between multiple genetic factors and environmental exposures.The genetic susceptibility of cancer has been previously established by epidemiological, twin and familial aggregation studies.The implication of a genetic component in the aetiology of cancer has driven enormous research endeavours to identify the genetic risk factors.The candidate gene association and linkage analysis approaches to identifying these genetic risk factors has, however, generated inconsistent results in the past.Notable advances have been achieved in recent years by genome-wide association studies (GWAS) – where several hundred–thousand single nucleotide polymorphisms (SNPs) throughout the human genome are interrogated for disease associations.Numerous novel genetic loci or genes have been implicated in a variety of cancers by GWAS.This significant progress in dissecting the germline genetic component of cancers is credited to the development of high-throughput genotyping technologies, which has enabled GWAS to be done more efficiently on thousands of samples.Similar to other complex diseases, most of the GWAS-identified SNPs for cancers have small effect sizes (OR <1.5) and collectively only account for a small fraction of the heritability of cancers.Several practical steps to further uncover additional genetic loci for cancers include (a) extending GWAS in different populations, (b) meta-analysis, (c) subgroup analysis and (d) a second tier of replication.In addition, other approaches should also be considered such as investigating rare variants or less common SNPs, targeted resequencing of the GWAS-identified loci, copy number variations and homozygosity mapping analysis.Keywords:cancer genetics;single nucleotide polymorphisms (SNPs);high-throughput genotyping technologies;genome-wide association studies (GWAS);cancer genome sequencing" @default.
• W1636320324 created "2016-06-24" @default.
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• W1636320324 date "2010-12-15" @default.
• W1636320324 modified "2023-09-30" @default.
• W1636320324 title "Genome-wide Association Studies of Cancers" @default.
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• W1636320324 doi "https://doi.org/10.1002/9780470015902.a0022659" @default.
• W1636320324 hasPublicationYear "2010" @default.
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