A Cohort Study of Cancer Risk in Relation to Family Histories of Cancer in the Utah Population Database

Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA.
Cancer (Impact Factor: 4.89). 05/2005; 103(9):1906-15. DOI: 10.1002/cncr.20989
Source: PubMed


It is well known that genetic variability affects the risk of many cancers, but details of the patterning of inherited cancer risk across different sites and age groups still are not well quantified.
The authors conducted a nested case-control study of the familial risk of 40 cancers based on a cohort of 662,515 individuals from the Utah Population Database. From 1 to 10 controls selected from the cohort were matched individually on gender, birth year, and birthplace to each cancer case; and familial standardized incidence ratios (FSIR) were calculated for both cases and controls. Conditional logistic regression was used to estimate relative risks and population-attributable risks (PARs) of cancer in relation to FSIR. Relative risks of cancer in first-degree through fifth-degree relatives of cases, compared with controls, were calculated using the proportional hazards methods. All analyses were adjusted for spouse affection status and Latter Day Saints church affiliation.
Thirty-five of 40 cancers exhibited positive associations between risk and FSIR, and 21 of those associations were statistically significant. PAR estimates were strikingly high for prostate carcinoma (57%), breast carcinoma (39%), colon carcinoma (32%), lip carcinoma (31%), chronic lymphocytic leukemia (35%), and melanoma (32%). Both the proportion and the number of all cancers attributable to family history peaked at 32% in the group ages 65-84 years and remained high in the group age >/= 85 years.
A substantial portion of cancer risk was attributable to familial factors. The patterns of familial cancer recurrence among distant relatives suggested that simple genetic mechanisms may explain much of the familiality of cancer.

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Available from: Richard A Kerber, Oct 23, 2014
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    • "Unfortunately, neither of these studies reports ACC as a separate entity, but summarizes all non-thyroid endocrine cancers in one category. The Utah study estimated the familial relative risk (FRR) (=relative risk in 1 st degree relatives) for non-thyroid endocrine cancers at 3.7 (0.3–45, 95% confidence interval) and the population attributable risk (PAR) (=the percentage of all cancers that can be attributed to a genetic predisposition) at 11% (0– 20%, 95% confidence interval) depending on age with the highest value (19%) for 65–85 yrs age group (Kerber et al. 2005). The Swedish registry found a standardized incidence ratio (SIR) (=observed cases/expected cases) for non-thyroid endocrine cancers of 2.46 (1.81– 3.26, 95% confidence interval) for family members with one affected parent, of 6.34 (4.44– 8.79, 95% confidence interval) for one affected sibling and of 70.28 (30.01–139.15, "
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    ABSTRACT: Our knowledge about inherited susceptibility to adrenocortical carcinoma (ACC) almost exclusively stems from experiences with familial cancer susceptibility syndromes, which are caused by single gene mutations (e.g. Li-Fraumeni syndrome (LFS)). Population-based studies are largely unavailable. ACC diagnosed during childhood is known to be commonly part of hereditary cancer syndromes. Childhood ACC is part of the classical tumor spectrum of LFS and Beckwith-Wiedemann syndrome (BWS). In adults ACC has been reported in patients with multiple endocrine neoplasia (MEN1), familial adenomatous polyposis coli (FAP) and neurofibromatosis type 1 (NF1). However, the evidence associating ACC with these syndromes is less well substantiated. Here, we will review the evidence for genetic predisposition in general and the association with known familial cancer susceptibility syndromes in particular. We will also review current recommendations regarding screening and surveillance of these patients as they apply to a specialized ACC or endocrine cancer clinic.
    Molecular and Cellular Endocrinology 12/2011; 351(1):66-70. DOI:10.1016/j.mce.2011.12.008 · 4.41 Impact Factor
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    • "There are few doubts that genetics plays a relevant role in increasing, or decreasing, the risk of cancer within components of the general population.88-90 Some studies suggest very simple genetic mechanisms may have a major role in many familial cancers;91,92 the Lynch Syndrome was perhaps the first confirmation of a mendelian cancer, in the colon.93,94 So too, yet unknown genetic factors linked to the reduced risk of cancer in schizophrenia could have a role in the etiology of the disorder. "
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    ABSTRACT: Patients diagnosed with schizophrenia have reduced fecundity and premature mortality (both accidental and violent) with no obvious compensatory advantages among kin. The prevalence of the disorder is around 0.7/1%, higher than the expected prevalence of spontaneous mutations. Genes favoring schizophrenia may have been positively selected in the environment of evolutionary adaptation. Literature on potential adaptive genes is reviewed within an evolutionary framework. Literature search on major scientific search engine (PubMed/Medline, Ovid/PsychInfo) on papers aimed at investigating potential pathways justifying a mutation-selection balanced model. Findings are presented with a narrative touch to favor readability and understanding. Reduced incidence of cancer in both patients diagnosed with schizophrenia and their siblings was reported worldwide. Such findings are notable given higher cancer risk factors in schizophrenia, i.e., smoking, alcohol abuse, obesity, poor diet, and poor adherence to therapy. Some genes involved in cancer proliferation might as well confer protective advantage in immune-surveillance, inflammation, vascular proliferation or apoptosis that otherwise will adversely affect early neurodevelopment. Evidence that reduced risk of certain somatic diseases is associated with schizophrenia is quite significant to progress in the evolutionary epidemiological analysis of psychopathology.
    Psychiatry investigation 06/2011; 8(2):77-88. DOI:10.4306/pi.2011.8.2.77 · 1.28 Impact Factor
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    • "However, for relatively late onset cancers, exemplified by prostate cancer here, larger numbers of familial cases are obtained by extending the data to older individuals. Data from the Utah population database suggest that familial cancers can be detected even at old ages [10]. Even hereditary cancers can be found at late age; when mutation screening for hereditary nonpolyposis colorectal cancer (HNPCC) was extended to older patients, mutation-positive individuals were detected with a median age of 61 years, compared to the long-held median age of 44 years [24]. "
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    ABSTRACT: The Swedish Family-Cancer Database has been used for some 10 years in the study of familial risks at all common sites. In the present paper we describe some of the main features of version VII of this Database, assembled in year 2006. This update included all residents in Sweden born or immigrated in 1932 and later (offspring) with their biological parents, a total of 11.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from years 1958 to 2004, including over 1.2 million first and multiple primary cancers and in situ tumours. We show one application of the Database in the study of familial risks in prostate cancer, with special reference to the modification of familial risk at the time of about 50% increase in incidence due to prostate specific antigen (PSA) screening. The familial risks for prostate cancer were 1.92 for sons of affected fathers, 3.03 for brothers and 5.44 for men with an affected father and an affected brother. Familial risk for prostate cancer according to the time since the first family member was diagnosed showed significant increases for two family members being diagnosed in the same year compared to 5+ years apart. Increased surveillance and the availability of PSA screening are the likely reasons for the overestimated familial relative risk shortly after the first diagnosis. This lead time bias should be considered in clinical counselling.
    Hereditary Cancer in Clinical Practice 12/2006; 4(4):186-92. DOI:10.1186/1897-4287-4-4-186 · 1.47 Impact Factor
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