| 1. |
- Campo, Chiara, et al.
(författare)
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Inherited variants in genes somatically mutated in thyroid cancer
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Tumour suppressor genes when mutated in the germline cause various cancers, but they can also be somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic well-differentiated thyroid cancer (WDTC). Methods We performed a two-stage case-control association study with a total of 2214 cases and 2108 healthy controls from an Italian population. By genotyping 34 single nucleotide polymorphisms (SNPs), we covered a total of 59 missense SNPs and SNPs located in the 5' and 3' untranslated regions (UTRs) of 10 different genes. Results The Italian1 series showed a suggestive association for 8 SNPs, from which three were replicated in the Italian2 series. The meta-analysis revealed a study-wide significant association for rs459552 (OR: 0.84, 95%CI: 0.75-0.94) and rs1800900 (OR: 1.15, 95%CI: 1.05-1.27), located in the APC and GNAS genes, respectively. The APC rs459552 is a missense SNP, located in a conserved amino acid position, but without any functional consequences. The GNAS rs1800900 is located at a conserved 5'UTR and according to the experimental ENCODE data it may affect promoter and histone marks in different cell types. Conclusions The results of this study yield new insights on WDTC, showing that inherited variants in the APC and GNAS genes can play a role in the etiology of thyroid cancer. Further studies are necessary to better understand the role of the identified SNPs in the development of WDTC and to functionally validate our in silico predictions.
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| 2. |
- Figlioli, Gisella, et al.
(författare)
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A comprehensive meta-analysis of case-control association studies to evaluate polymorphisms associated with the risk of differentiated thyroid carcinoma
- 2016
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1055-9965. ; 25:4, s. 700-713
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Tidskriftsartikel (refereegranskat)abstract
- Background: Linkage analyses and association studies suggested that inherited genetic variations play a role in the development of differentiated thyroid carcinoma (DTC). Methods: We combined the results from a genome-wide association study (GWAS) performed by our group and frompublished studies onDTC. With a first approach, we evaluated whether a SNP published as associated with the risk of DTC could replicate in our GWAS (using FDR as adjustment for multiple comparisons). With the second approach, meta-analyses were performed between literature and GWAS when both sources suggested an association, increasing the statistical power of the analysis. Results: rs1799814 (CYP1A1), rs1121980 (FTO), and 3 SNPs within 9q22 (rs965513, rs7048394, and rs894673) replicated the associations described in the literature. In addition, the meta-analyses between literature and GWAS revealed 10 more SNPs within 9q22, six within FTO, two within SOD1, and single variations within HUS1, WDR3, UGT2B7, ALOX12, TICAM1, ATG16L1, HDAC4, PIK3CA, SULF1, IL11RA, VEGFA, and 1p31.3, 2q35, 8p12, and 14q13. Conclusion: This analysis confirmed several published risk loci that could be involved in DTC predisposition. Impact: These findings provide evidence for the role of germline variants in DTC etiology and are consistent with a polygenic model of the disease.
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| 3. |
- Lascorz, Jesus, et al.
(författare)
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Consensus Pathways Implicated in Prognosis of Colorectal Cancer Identified Through Systematic Enrichment Analysis of Gene Expression Profiling Studies
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: A large number of gene expression profiling (GEP) studies on prognosis of colorectal cancer (CRC) has been performed, but no reliable gene signature for prediction of CRC prognosis has been found. Bioinformatic enrichment tools are a powerful approach to identify biological processes in high-throughput data analysis. Principal Findings: We have for the first time collected the results from the 23 so far published independent GEP studies on CRC prognosis. In these 23 studies, 1475 unique, mapped genes were identified, from which 124 (8.4%) were reported in at least two studies, with 54 of them showing consisting direction in expression change between the single studies. Using these data, we attempted to overcome the lack of reproducibility observed in the genes reported in individual GEP studies by carrying out a pathway-based enrichment analysis. We used up to ten tools for overrepresentation analysis of Gene Ontology (GO) categories or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in each of the three gene lists (1475, 124 and 54 genes). This strategy, based on testing multiple tools, allowed us to identify the oxidative phosphorylation chain and the extracellular matrix receptor interaction categories, as well as a general category related to cell proliferation and apoptosis, as the only significantly and consistently overrepresented pathways in the three gene lists, which were reported by several enrichment tools. Conclusions: Our pathway-based enrichment analysis of 23 independent gene expression profiling studies on prognosis of CRC identified significantly and consistently overrepresented prognostic categories for CRC. These overrepresented categories have been functionally clearly related with cancer progression, and deserve further investigation.
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| 4. |
- Zheng, Guoqiao, et al.
(författare)
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Familial risks of ovarian cancer by age at diagnosis, proband type and histology
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is a heterogeneous disease. Data regarding familial risks for specific proband, age at diagnosis and histology are limited. Such data can assist genetic counseling and help elucidate etiologic differences among various histologic types of ovarian malignancies. By using the Swedish Family-Cancer Database, we calculated relative risks (RRs) for detailed family histories using a two-way comparison, which implied e.g. estimation of RRs for overall ovarian cancer when family history was histology-specific ovarian cancer, and conversely, RRs for histology-specific ovarian cancer when family history was overall ovarian cancer. In families of only mother, only sisters or both mother and sisters diagnosed with ovarian cancer, cancer risks for ovary were 2.40, 2.59 and 10.40, respectively; and were higher for cases diagnosed before the age of 50 years. All histological types showed a familial risk in two-way analyses, except mucinous and sex cord-stromal tumors. RRs for concordant histology were found for serous (2.47), endometrioid (3.59) and mucinous ovarian cancers (6.91). Concordant familial risks were highest for mucinous cancer; for others, some discordant associations, such as endometrioid-undifferentiated (9.27) and serousundifferentiated (4.80), showed the highest RRs. Familial risks are high for early-onset patients and for those with multiple affected relatives. Sharing of different histological types of ovarian cancer is likely an indication of the complexity of the underlying mechanisms.
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