International Agency for Research on Cancer

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: Population & Cancer. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

Genetic and Histopathologic Evaluation of BRCA1 and BRCA2 DNA Sequence Variants of Unknown Clinical Significance

Abstract: Classification of rare missense variants as neutral or disease causing is a challenge and has important implications for genetic counseling. A multifactorial likelihood model for classification of unclassified variants in BRCA1 and BRCA2 has previously been developed, which uses data on co-occurrence of the unclassified variant with pathogenic mutations in the same gene, cosegregation of the unclassified variant with affected status, and Grantham analysis of the fit between the missense substitution and the evolutionary range of variation observed at its position in the protein. We have further developed this model to take into account relevant features of BRCA1- and BRCA2-associated tumors, such as the characteristic histopathology and immunochemical profiles associated with pathogenic mutations in BRCA1, and the fact that approximately 80% of tumors from BRCA1 and BRCA2 carriers undergo inactivation of the wild-type allele by loss of heterozygosity. We examined 10 BRCA1 and 15 BRCA2 unclassified variants identified in Australian, multiple-case breast cancer families. By a combination of genetic, in silico, and histopathologic analyses, we were able to classify one BRCA1 variant as pathogenic and six BRCA1 and seven BRCA2 variants as neutral. Five of these neutral variants were also found in at least 1 of 180 healthy controls, suggesting that screening a large number of appropriate controls might be a useful adjunct to other methods for evaluation of unclassified variants.

A million africans a year dying from cancer by 2030: what can cancer research and control offer to the continent?

Abstract: In Africa, there were an estimated 681,000 new cancer cases and 512,000 deaths in 2008. Projections to 2030 show a startling rise, with corresponding figures of 1.27 million cases and 0.97 million deaths resulting from population growth and aging alone. The figures make no assumptions about incidence rates which may increase due to the further introduction of tobacco and a more westernized lifestyle. The current situation in many parts of Africa with respect to health care systems suggests that improved cancer treatment would be an insufficient response to this increasing burden. Much could be achieved through cancer prevention by applying current knowledge about major risk factors and the natural history of the disease. For example, vaccination against hepatitis B virus and human papilloma viruses would prevent the occurrence of two of the most common cancers in Africa, liver and cervix, respectively, in the long-term. Strong measures to prevent the widespread introduction of tobacco must be a priority. Early detection and treatment of cervical and breast cancers using approaches applicable now in Africa would provide immediate value, as would the management of human immunodeficiency virus (HIV) infection in respect to HIV-associated malignancies. In parallel, further research is needed into the causes of cancer and the barriers to implementation of promising prevention strategies. Underpinning all is the need for African governments to look forward and prioritize cancer through national cancer control plans, to invest in public health infrastructure and to ensure the adequate training and support for people in cancer prevention and control. Given this core commitment from within Africa, international partners can provide complementary support in a cooperation that permits action now to mitigate the impending tragedy of cancer in the continent of Africa.

Validity of a short questionnaire to assess physical activity in 10 European countries

Abstract: To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnair ...

Correlation among pathology, genotype, and patient outcomes in glioblastoma.

Abstract: Glioblastomas are histologically and genetically heterogeneous.We have investigated to what extent histologic features reflect thegenetic profile and whether they are predictive of clinical outcome.Key histologic characteristics, including major cell types (smallcell, nonsmall cell), other components such as oligodendroglialcomponents, gemistocytes, multinucleated giant cells, as well asnecrosis and microvascular proliferation, of 420 cases of glioblas-toma within a population-based study (1) were reassessed andcorrelated with patients_ clinical outcome and key genetic alter-ations. EGFR amplification and p16 INK4a homozygous deletionwere significantly more frequent in small cell glioblastomas than innonsmall cell glioblastomas (EGFR, 46% vs 26%, p = 0.0002;p16 INK4a 39% vs 25%, p = 0.0167). Multivariate analyses withadjustment for age and gender showed that small cell glioblastomashad frequent EGFR amplification and p16 INK4a deletion butinfrequent PTEN mutations. An oligodendroglial component wasdetected in 20% of glioblastomas; these patients were significantlyyounger (54.4 T 13.6 vs 59.2 T 13.8 years; p = 0.0049) and survivedlonger (10.3 T 8.3 vs 8.2 T 8.4 months; p = 0.0647). However,multivariate analyses with adjustment for age and gender did notshow the presence of an oligodendroglial component to bepredictive of longer survival. After adjustment for age and gender,LOH 1p was associated with longer survival (hazard ratio, 0.7; 95%confidence interval [CI], 0.5Y1.0), whereas LOH 10q was associ-ated with shorter survival (hazard ratio, 1.4; 95% CI, 1.0Y1.8) ofpatients with glioblastoma. Glioblastomas containing Q5% multi-nucleated giant cells showed more frequent TP53 mutation andinfrequent EGFR amplification than those containing <5% multi-nucleated giant cells (TP53, 45% vs 24%, p = 0.0001; EGFR, 24%vs 42%, p = 0.0005). Vascular proliferation was observed in allglioblastomas, whereas large ischemic and/or pseudopalisadingnecrosis was observed in 366 of 420 (87%) cases. Glioblastomaswith necrosis were associated with older age (59.2 T 13.3 vs 51.6 T15.3 years; p = 0.0001) and shorter survival (7.9 T 6.8 vs 12.9 T14.2 months; p = 0.0017). Multivariate analyses with adjustment forageandgenderconfirmedthisobservation(hazardratio,1.5;95%CI,1.1Y2.0). Multivariate analysis with adjustment for age and gendershowed that necrosis was significantly associated with wild-type TP53and absence of an oligodendroglial component. These results suggestthat some histologic features in g lioblastomas are associated withspecific genetic alterations and with clinical outcome.Key Words: EGFR amplification, Glioblastoma, LOH 1p, LOH19q, Necrosis, Oligodendroglial component, p16