SOURCES AND EFFECTS OF IONIZING RADIATION : United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes

1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

In December 1997, the National Cancer Institute sponsored "The International Workshop on Microsatellite Instability and RER Phenotypes in Cancer Detection and Familial Predisposition," to review and unify the field. The following recommendations were endorsed at the workshop. (a) The form of genomic instability associated with defective DNA mismatch repair in tumors is to be called microsatellite instability (MSI). (b) A panel of five microsatellites has been validated and is recommended as a reference panel for future research in the field. Tumors may be characterized on the basis of: high-frequency MSI (MSI-H), if two or more of the five markers show instability (i.e., have insertion/deletion mutations), and low-frequency MSI (MSI-L), if only one of the five markers shows instability. The distinction between microsatellite stable (MSS) and low frequency MSI (MSI-L) can only be accomplished if a greater number of markers is utilized. (c) A unique clinical and pathological phenotype is identified for the MSI-H tumors, which comprise approximately 15% of colorectal cancers, whereas MSI-L and MSS tumors appear to be phenotypically similar. MSI-H colorectal tumors are found predominantly in the proximal colon, have unique histopathological features, and are associated with a less aggressive clinical course than are stage-matched MSI-L or MSS tumors. Preclinical models suggest the possibility that these tumors may be resistant to the cytotoxicity induced by certain chemotherapeutic agents. The implications for MSI-L are not yet clear. (d) MSI can be measured in fresh or fixed tumor specimens equally well; microdissection of pathological specimens is recommended to enrich for neoplastic tissue; and normal tissue is required to document the presence of MSI. (e) The "Bethesda guidelines," which were developed in 1996 to assist in the selection of tumors for microsatellite analysis, are endorsed. (f) The spectrum of microsatellite alterations in noncolonic tumors was reviewed, and it was concluded that the above recommendations apply only to colorectal neoplasms. (g) A research agenda was recommended.

https://cancerres.aacrjournals.org/content/canres/58/22/5248.full.pdf

A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: Development of International Criteria for the Determination of Microsatellite Instability in Colorectal Cancer

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0040297&type=printable

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(03)12384-7.pdf

Association between telomere length in blood and mortality in people aged 60 years or older

Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no differences among the rat groups in survival, body weight, inflammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. AS-expressing C. elegans fed on curli-producing bacteria also had enhanced AS aggregation. These results suggest that bacterial amyloid functions as a trigger to initiate AS aggregation through cross-seeding and also primes responses of the innate immune system.

/pdf/exposure-to-the-functional-bacterial-amyloid-protein-curli-354miuciu9.pdf

Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans.

Objective\p=m-\Thepurpose of this study is to assess the impact of family history on the risk of developing breast cancer Design\p=m-\Acase-control study design was used Setting\p=m-\Toprovide a comprehensive assessment of family history risk, we used the Utah Population Database, a linked database compiled of genealogy data of the descendants of Mormon pioneer families, cancer data from the Utah Cancer Registry, and mortality data from the Utah Department of Vital Statistics Patients\p=m-\Allwomen diagnosed with breast cancer who were in the genealogy database and the Utah Cancer Registry were included Controls were women selected from the genealogy, who like cases had no record of previous cancer They were matched to the cases by age and place of birth Outcome\p=m-\Severaldefinitions of family history were used The total familial risk variable, developed to work effectively in the Utah Genealogy Database, accounts for all family members, their degree of relatedness to the case, and the amount of time they were observed for possible cancer diagnosis Results\p=m-\Athreefold increase in risk, estimated by the odds ratio (OR), of breast cancer among those with the highest family history score (6% of cases) was observed when compared with those with the lowest family history score The OR for women with a first-degree relative with breast cancer was 245 (95% confidence interval [Cl], 184 to 306) If the nearest relative was a second-degree relative, the OR was 182 (95% Cl, 139 to 224); if the nearest relative was a third-degree relative, the OR was 135 (95% Cl, 107 to 164) A slightly greater risk was observed if the first-degree relative was a woman's mother (OR, 244; 95% Cl, 177 to 342) rather than a sister (OR, 201; 95% Cl, 166 to 243) Among subjects diagnosed before the age of 50 years, the disease experience of relatives prior to age 50 was most important, while for older subjects the experience of relatives of all ages was of roughly equal importance Women who developed contralateral breast cancer within 3 years of initial diagnosis were nearly 10 times as likely as women without breast cancer to have a first-degree relative with breast cancer Based on the risk estimates in this study, we have estimated that approximately 17% to 19% of breast cancer in the population could be attributed to family history Women who had a first-degree relative with colon cancer had a 30% increased risk of breast cancer Conclusions\p=m-\Inthis study population, women with a family history of breast cancer, even if the nearest relative with breast cancer is a third-degree relative, are at increased risk of the disease (JAMA 1993;270:1563-1568)

A Comprehensive Evaluation of Family History and Breast Cancer Risk

Objective. —The purpose of this study is to assess the impact of family history on the risk of developing breast cancer. Design. —A case-control study design was used. Setting. —To provide a comprehensive assessment of family history risk, we used the Utah Population Database, a linked database compiled of genealogy data of the descendants of Mormon pioneer families, cancer data from the Utah Cancer Registry, and mortality data from the Utah Department of Vital Statistics. Patients. —All women diagnosed with breast cancer who were in the genealogy database and the Utah Cancer Registry were included. Controls were women selected from the genealogy, who like cases had no record of previous cancer. They were matched to the cases by age and place of birth. Outcome. —Several definitions of family history were used. The total familial risk variable, developed to work effectively in the Utah Genealogy Database, accounts for all family members, their degree of relatedness to the case, and the amount of time they were observed for possible cancer diagnosis. Results. —A threefold increase in risk, estimated by the odds ratio (OR), of breast cancer among those with the highest family history score (6% of cases) was observed when compared with those with the lowest family history score. The OR for women with a first-degree relative with breast cancer was 2.45 (95% confidence interval [Cl], 1.84 to 3.06). If the nearest relative was a second-degree relative, the OR was 1.82 (95% Cl, 1.39 to 2.24); if the nearest relative was a third-degree relative, the OR was 1.35 (95% Cl, 1.07 to 1.64). A slightly greater risk was observed if the first-degree relative was a woman's mother (OR, 2.44; 95% Cl, 1.77 to 3.42) rather than a sister (OR, 2.01; 95% Cl, 1.66 to 2.43). Among subjects diagnosed before the age of 50 years, the disease experience of relatives prior to age 50 was most important, while for older subjects the experience of relatives of all ages was of roughly equal importance. Women who developed contralateral breast cancer within 3 years of initial diagnosis were nearly 10 times as likely as women without breast cancer to have a first-degree relative with breast cancer. Based on the risk estimates in this study, we have estimated that approximately 17% to 19% of breast cancer in the population could be attributed to family history. Women who had a first-degree relative with colon cancer had a 30% increased risk of breast cancer. Conclusions. —In this study population, women with a family history of breast cancer, even if the nearest relative with breast cancer is a third-degree relative, are at increased risk of the disease. ( JAMA . 1993;270:1563-1568)

https://jamanetwork.com/journals/JAMA/articlepdf/408683/jama_270_13_033.pdf

A Comprehensive Evaluation of Family History and Breast Cancer Risk: The Utah Population Database

The authors linked interview data drawn from Utah participants in the Diet, Activity, and Reproduction in Colon Cancer (DARCC) Study (1992-1995) to genealogic and cancer information contained in the Utah Population Database (UPDB). They evaluated the sensitivity of subjects' reports of familial cancers and measured the overall agreement between reported and database records with the kappa (kappa) statistic. They calculated odds ratios from logistic regression to compare the relative risk estimates that would result from use of either data set (or both data sets). Overall, 37.6% (331 of 881) of the Utah DARCC subjects were linked to the UPDB genealogy. High sensitivities were observed for subjects' reports of breast (83%), colorectal (73%), and prostate (70%) cancers, while ovarian (60%) and uterine (30%) cancers were not reported as well. Results for kappa were similar, with values of 0.63 for breast cancer and 0.56 for colorectal cancer. Although the observed kappa s of 0.36 and 0.25 for ovarian and uterine cancers, respectively, exceeded chance expectations, the agreement between subjects' reports and database records was unimpressive. No consistent difference was observed between cases and controls in the accuracy of self-reports. In general, higher sensitivities were observed among younger subjects than older subjects; females reported family histories of cancer only slightly better than males. A college education was not consistently associated with more accurate reporting of family history of cancer. These results indicate that subjects in a case-control study are able to report accurately family histories of several common kinds of cancer and that they can do so without observable recall bias. The accuracy of self-reports may not be adequate for reproductive tract cancers and cancers such as rectal cancer that are frequently confused with cancers of similar organs.

Richard A. Kerber

Papers

Association between telomere length in blood and mortality in people aged 60 years or older

Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans.

A Comprehensive Evaluation of Family History and Breast Cancer Risk

A Comprehensive Evaluation of Family History and Breast Cancer Risk: The Utah Population Database

Comparison of self-reported and database-linked family history of cancer data in a case-control study