Institution
International Agency for Research on Cancer
Government•Lyon, France•
About: International Agency for Research on Cancer is a government organization based out in Lyon, France. It is known for research contribution in the topics: Cancer & Population. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.
Topics: Cancer, Population, Breast cancer, Risk factor, European Prospective Investigation into Cancer and Nutrition
Papers published on a yearly basis
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German Cancer Research Center1, St. Jude Children's Research Hospital2, Heidelberg University3, Institut Gustave Roussy4, University Hospital Heidelberg5, University of Calgary6, University of Copenhagen7, University Health Network8, University of Utah9, Semmelweis University10, McGill University11, Asan Medical Center12, Masaryk University13, Stanford University14, The Chinese University of Hong Kong15, University of California, San Francisco16, Emory University17, Humboldt University of Berlin18, Children's Hospitals and Clinics of Minnesota19, University of Texas Southwestern Medical Center20, Children's Hospital at Westmead21, Boston Children's Hospital22, University of Duisburg-Essen23, Oslo University Hospital24, University of Oslo25, Karolinska Institutet26, University of Gothenburg27, International Agency for Research on Cancer28, Swiss Tropical and Public Health Institute29, University of Bern30, University of Zurich31, University of Würzburg32, Massachusetts Institute of Technology33, University Hospital of Basel34, Charles University in Prague35, Hannover Medical School36, BC Cancer Agency37, University of Hamburg38, University of Toronto39, University of Cambridge40
TL;DR: The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup, and survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.
Abstract: Summary Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU , and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB SHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MB SHH subgroup). Patients with germline APC mutations developed MB WNT and accounted for most (five [71%] of seven) cases of MB WNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MB SHH . Germline TP53 mutations presented only in childhood patients in the MB SHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MB SHH , MB Group3 , and MB Group4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40–69) and 5-year overall survival was 65% (95% CI 52–81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MB WNT and MB SHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Funding German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.
229 citations
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TL;DR: Parthenolide is the first small molecule found to be selective against cancer stem cells (CSC), which it achieves by targeting specific signaling pathways and killing cancer from its roots.
229 citations
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TL;DR: Heterozygous Men1 mutant mice developed the same range of major endocrine tumors as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage tumor progression with metastatic potential.
Abstract: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the occurrence of multiple endocrine tumors of the parathyroid, pancreas, and anterior pituitary in patients. To study tumorigenesis related to the MEN1 syndrome, we have generated Men1 knockout mice using the gene targeting approach. Heterozygous Men1 mutant mice developed the same range of major endocrine tumors as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage tumor progression with metastatic potential. In particular, extrapancreatic gastrinoma, pancreatic glucagonoma, and mixed hormone-producing tumors in islets were observed. In addition, there was a high incidence of gonadal tumors of endocrine origin, i.e. Leydig cell tumors, and ovary sex-cord stromal cell tumors in heterozygous Men1 mutant mice. Hormonal disturbance, such as abnormal PTH and insulin levels, was also observed in these mice. These tumors were associated with loss of heterozygosity of the wild-type Men1 allele, suggesting that menin is involved in suppressing the development of these endocrine tumors. All of these features are reminiscent of MEN1 symptoms in humans and establish heterozygous Men1 mutant mice as a suitable model for this disease.
229 citations
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TL;DR: Adenomas of both colon and rectum were more frequent in men than in women, contrary to findings with colon cancer, and the sex ratio of adenomas changed with age, from slightly below unity in persons under 65, to above unity for those aged 65 and over.
Abstract: The results of this multicentre autopsy study emphasize the relationship between the prevalence of adenomas and the incidence of large-bowel cancer. The highest proportion of autopsies with adenomas was observed in the area with the highest incidence of large-bowel cancer. The segmental distribution of adenomas within the colon was found to be similar to the site distribution of cancer. However, the lowest proportion of adenomas was found in the rectum, the segment in which cancer is most frequent. The latter finding suggests that either the adenoma-carcinoma sequence is a less important pathway in the pathogenesis of rectal cancer, or that more rectal than colonic adenomas become malignant. The high proportion of hyperplastic polyps in the rectum, and statistically significant regional differences following the same patterns as the incidence of rectal cancer suggest that there could be at least an indirect relationship between hyperplastic polyps and cancer of the rectum. Adenomas of both colon and rectum were more frequent in men than in women, contrary to findings with colon cancer. However, as for colon cancer, the sex ratio of adenomas changed with age, from slightly below unity in persons under 65, to above unity for those aged 65 and over. A major difficulty that emerged was the histological identification of "polyps" because of the degree of autolysis of epithelial cells in the mucous membrane, and this difficulty largely contributed to the poor consistency of histological reporting. Regular consistency surveys of histological preparations should be recommended in any type of multicentre study in which histological examination is included.
229 citations
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University College London1, University of Edinburgh2, Netherlands Cancer Institute3, Peter MacCallum Cancer Centre4, University of Melbourne5, University of Cambridge6, University of St Andrews7, University of Aberdeen8, John Hunter Hospital9, International Agency for Research on Cancer10, University of Utah11, Trinity College, Dublin12, Max Delbrück Center for Molecular Medicine13, Cambridge University Hospitals NHS Foundation Trust14, Curie Institute15, Leeds Teaching Hospitals NHS Trust16, Erasmus University Rotterdam17, Leiden University18, German Cancer Research Center19, University of Pennsylvania20
TL;DR: The results indicate that non-BRCA1/2 breast cancers differ histologically from both BRC a1 and BRCA 2 breast cancers and are overall of lower grade, and suggest thatNon-B RCA 1/2 Breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.
Abstract: Breast cancers arising in carriers of mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, differ histologically from each other and from breast cancers unselected for a family history. However, a substantial proportion of families with multiple cases of breast cancer is not attributable to these two genes (non-BRCA1/2 families). We have now characterized the pathology of 82 breast cancers from non-BRCA1/2 families. Breast cancers in non-BRCA1/2 families were of lower grade (P = 0.0018), showed fewer mitoses (P < 0.0001), less nuclear pleomorphism (P = 0.0014), less lymphocytic infiltrate (P < 0.0001), a lesser extent of the tumor with a continuous pushing margin (P = 0.004), a lesser extent of the tumor composed of solid sheets of cells (P = 0.0047), less necrosis (P = 0.002), and wereparison with BRCA2 tumors, non-BRCA1/2 tumors were lower grade (P = 0.017) and exhibited less pleomorphism (P = 0.01) and more tubule formation (P = 0.05). In comparison with control breast cancers unselected for a family history of the disease, non-BRCA1/2 tumors were of significantly lower grade (P = 0.001), showed less pleomorphism (P = 0.0002), and had a lower mitotic count (P = 0.003). The results indicate that non-BRCA1/2 breast cancers differ histologically from both BRCA1 and BRCA2 breast cancers and are overall of lower grade. They also suggest that non-BRCA1/2 breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.
229 citations
Authors
Showing all 3012 results
Name | H-index | Papers | Citations |
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David J. Hunter | 213 | 1836 | 207050 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Elio Riboli | 158 | 1136 | 110499 |
Silvia Franceschi | 155 | 1340 | 112504 |
Stephen J. Chanock | 154 | 1220 | 119390 |
Paolo Boffetta | 148 | 1455 | 93876 |
Timothy J. Key | 146 | 808 | 90810 |
Hans-Olov Adami | 145 | 908 | 83473 |
Joseph J.Y. Sung | 142 | 1240 | 92035 |
Heiner Boeing | 140 | 1024 | 92580 |
Anne Tjønneland | 139 | 1345 | 91556 |
Kim Overvad | 139 | 1196 | 86018 |
Sheila Bingham | 136 | 519 | 67332 |
Pasi A. Jänne | 136 | 685 | 89488 |
Peter Kraft | 135 | 821 | 82116 |