Animal model studies and human epidemiological studies have shown that some infectious diseases develop primarily in individuals with an inherited predisposition. A heritable contribution to the development of severe influenza virus infection (i.e., that which results in death) has not previously been hypothesized or tested. Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza. Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza.
BackgroundProstate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history.MethodsA retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from males with no PC family history (without PC in first, second, or third degree relatives). RRs were determined for a variety of constellations, for example, number of first through third degree relatives; named (grandfather, father, uncle, cousins, brothers); maternal, paternal relationships, and age of onset.ResultsIn the 635,443 males analyzed, 18,105 had PC. First-degree RRs ranged from 2.46 (=1 first-degree relative affected, CI = 2.39–2.53) to 7.65 (=4 first-degree relatives affected, CI = 6.28–9.23). Second-degree RRs for probands with 0 affected first-degree relatives ranged from 1.51 (≥1 second-degree relative affected, CI = 1.47–1.56) to 3.09 (≥5 second-degree relatives affected, CI = 2.32–4.03). Third-degree RRs with 0 affected first- and 0 affected second-degree relatives ranged from 1.15 (≥1 affected third-degree relative, CI = 1.12–1.19) to 1.50 (≥5 affected third-degree relatives, CI = 1.35–1.66). RRs based on age at diagnosis were higher for earlier age at diagnoses; for example, RR = 5.54 for ≥1 first-degree relative diagnosed before age 50 years (CI = 1.12–1.19) and RR = 1.78 for >1 second-degree relative diagnosed before age 50 years, CI = 1.33, 2.33. RRs for equivalent maternal versus paternal family history were not significantly different.ConclusionsA more complete PC family history using close and distant relatives and age at diagnosis results in a wider range of estimates of individual RR that are potentially more accurate than RRs estimated from summary family history. The presence of PC in second- and even third-degree relatives contributes significantly to risk. Maternal family history is just as significant as paternal family history. PC RRs based on a proband's complete constellation of affected relatives will allow patients and care providers to make more informed screening, monitoring, and treatment decisions. Prostate 75:390–398, 2015. © 2014 Wiley Periodicals, Inc.
original research article Purpose: Cancer is familial; yet known cancer predisposition genes, as well as recognized environmental factors, explain only a small percentage of familial cancer clusters. This population-based description of cancer clustering describes patterns of cancer coaggregation suggestive of a genetic predisposition. methods: Using a computerized genealogy of Utah families linked to a statewide cancer registry, we estimated the relative risks for 36 different cancer sites in first-, second-, and third-degree relatives of cancer cases, for each cancer site individually, and between cancer sites. We estimated the sex-and birth-year-specific rates for cancer using 1 million individuals in the resource. We applied these rates to groups of cases or relatives and compared the observed and expected numbers of cancers to estimate relative risks.Results: Many cancer sites show significantly elevated relative risks among distant relatives for cancer of the same site, strongly supporting a heritable contribution. Multiple combinations of cancer sites were observed among first-, second-, and third-degree relatives, suggesting the existence of heritable syndromes involving more than one cancer site.conclusion: This complete description of coaggregation of cancer by site in a well-defined population provides a set of observations supporting heritable cancer predispositions and may support the existence of genetic factors for many different cancers.Genet Med 2012:14(1):107-114
BackgroundChronic Fatigue Syndrome (CFS) came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV) or other murine leukemia related retroviruses (MLV) might also suggest underlying genetic implications within the host immune system.MethodsWe present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases.ResultsWe observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p <0.001) and distant relationships (p = 0.010). We also observed significant excess CFS relative risk among first (2.70, 95% CI: 1.56-4.66), second (2.34, 95% CI: 1.31-4.19), and third degree relatives (1.93, 95% CI: 1.21-3.07).ConclusionsThese analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.
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