scholarly journals Genomic Risk Factors for Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5137
Author(s):  
Dhanya Ramachandran ◽  
Thilo Dörk
Keyword(s):  
Cervical Cancer ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Meta Analysis ◽  
Invasive Cervical Cancer ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Risk Variants ◽  
Genetic Heritability ◽  
Corroborative Evidence

Cervical cancer is the fourth common cancer amongst women worldwide. Infection by high-risk human papilloma virus is necessary in most cases, but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability in the range of other gynaecological cancers, only few genomic susceptibility loci have been identified thus far. Various case-control association studies have found corroborative evidence for several independent risk variants at the 6p21.3 locus (HLA), while many reports of associations with variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

scholarly journals Genomic Risk Factors for Cervical Cancer

2021 ◽  
Author(s):  
Dhanya Ramachandran ◽  
Thilo Dörk
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Meta Analysis ◽  
Invasive Cervical Cancer ◽  
Recurrent Infection ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci

Cervical cancer is the fourth common cancer amongst women worldwide. Environmental factors such as smoking and obesity, and recurrent infection by high-risk human papillomavirus subtypes are known to promote progression towards invasive cervical disease. Infection by high-risk HPV is necessary in most cases but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability of between 27-36%, known genetic susceptibility loci that may be tumorigenic or influence host response to infection, only account for a small fraction of heritable risk factors so far. Various biobank-driven population based studies and meta-analyses have found corroborative evidence for several risk variants at the 6p21.3 locus (HLA), while many reports of variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

scholarly journals A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Nada A. Al-Tassan ◽  
Nicola Whiffin ◽  
Fay J. Hosking ◽  
Claire Palles ◽  
Susan M. Farrington ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Association Studies ◽  
Meta Analysis ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Risk Variants ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Long Non Coding Rna

Abstract Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 × 10−8, odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 × 10−8; OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 × 10-8; OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.

scholarly journals Risks and Function of Breast Cancer Susceptibility Alleles

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3953
Author(s):  
Saeideh Torabi Dalivandan ◽  
Jasmine Plummer ◽  
Simon A. Gayther
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Disease Risk ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Treatment Strategies ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Degree Relative ◽  
Risk Variants

Family history remains one of the strongest risk factors for breast cancer. It is well established that women with a first-degree relative affected by breast cancer are twice as likely to develop the disease themselves. Twins studies indicate that this is most likely due to shared genetics rather than shared epidemiological/lifestyle risk factors. Linkage and targeted sequencing studies have shown that rare high- and moderate-penetrance germline variants in genes involved in the DNA damage response (DDR) including BRCA1, BRCA2, PALB2, ATM, and TP53 are responsible for a proportion of breast cancer cases. However, breast cancer is a heterogeneous disease, and there is now strong evidence that different risk alleles can predispose to different subtypes of breast cancer. Here, we review the associations between the different genes and subtype-specificity of breast cancer based on the most comprehensive genetic studies published. Genome-wide association studies (GWAS) have also been used to identify an additional hereditary component of breast cancer, and have identified hundreds of common, low-penetrance susceptibility alleles. The combination of these low penetrance risk variants, summed as a polygenic risk score (PRS), can identify individuals across the spectrum of disease risk. However, there remains a substantial bottleneck between the discovery of GWAS-risk variants and their contribution to tumorigenesis mainly because the majority of these variants map to the non-protein coding genome. A range of functional genomic approaches are needed to identify the causal risk variants and target susceptibility genes and establish their underlying role in disease biology. We discuss how the application of these multidisciplinary approaches to understand genetic risk for breast cancer can be used to identify individuals in the population that may benefit from clinical interventions including screening for early detection and prevention, and treatment strategies to reduce breast cancer-related mortalities.

scholarly journals A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

2012 ◽  
Vol 21 (24) ◽  
pp. 5373-5384 ◽  
Author(s):  
Afshan Siddiq ◽  
Fergus J. Couch ◽  
Gary K. Chen ◽  
Sara Lindström ◽  
Diana Eccles ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Genome Wide
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