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1.
Int J Colorectal Dis ; 35(8): 1559-1566, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32388603

RESUMO

BACKGROUND AND AIMS: Women are at risk of colorectal cancer (CRC) during pregnancy but this fact is underappreciated. We performed a population-based study to evaluate the rate, predictors, and familial risk for pregnancy associated CRC in Utah. METHODS: All newly diagnosed cases of CRC between 1973 and 2014 were obtained from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. RESULTS: Of the 12,886 females diagnosed with CRC, 73 were diagnosed with CRC (0.57%) during the period of obstetric delivery/childbirth. Pregnancy associated CRC was diagnosed at a mean age of 31.9 years, and cancers were less frequently located in the proximal colon compared with women with non-pregnancy associated CRC. First-degree relatives of cases with pregnancy associated CRC had a nearly threefold higher risk of CRC (OR, 2.76; 95% CI, 1.26-6.01) compared with relatives of CRC-free individuals. CONCLUSIONS: Of women diagnosed with CRC, less than 1% were diagnosed during or soon after obstetric delivery/childbirth. Relatives of these patients have a nearly threefold greater risk of CRC than those without a family history of CRC. These results provide physicians with data to guide the care of patients and their relatives with pregnancy associated CRC.


Assuntos
Neoplasias Colorretais , Predisposição Genética para Doença , Adulto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Feminino , Humanos , Gravidez , Sistema de Registros , Fatores de Risco , Utah/epidemiologia
2.
J Gastroenterol ; 54(12): 1106-1112, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31240435

RESUMO

INTRODUCTION: Pancreas adenocarcinoma (PC) has an undefined hereditary component. We quantified the familial risk of PC among relatives of patients diagnosed with PC and stratified it based on anatomic location of PC and age and sex of the proband. METHODS: This is a retrospective, population-based, case-control study of PC diagnosed in Utah between 1980 and 2011. The Utah population database and cancer registry were used to identify index patients with PC. The risk of PC in first-degree relatives (FDRs), second-degree relatives (SDRs), and first cousins (FCs) of probands was compared with randomly selected sex- and age-matched population controls. RESULTS: A total of 4,095 patients and 40,933 controls were identified. The relative risk (RR) of PC was 1.76 (95% CI 1.35-2.29) in FDRs, 1.42 (95% CI 1.18-1.7) in SDRs and 1.08 (95% CI 0.95-1.23) in FCs of probands compared to relatives of PC-free controls. The RR were elevated in FDRs (1.96, 95% CI 1.45-2.65), SDRs (1.54, 95% CI 1.19-1.98) and FCs (1.18, 95% CI 1.0-1.64) of female probands. Among probands diagnosed as < 65 years, RR was 2.12 (95% CI 1.37-3.28) in FDRs, 1.94 (95% CI 1.44-2.62) in SDRs, and 1.28 (95% CI 1.0-1.64) in FCs. Overall, the RR for PC was elevated in FDRs regardless of the anatomic location of PC. DISCUSSION: There is an increased risk of PC in FDR and more distant relatives of patients with PC. Relatives of female patients with PC and patients diagnosed at age < 65 years are at a significantly increased risk of PC.


Assuntos
Adenocarcinoma/epidemiologia , Carcinoma/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Estudos de Casos e Controles , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Utah/epidemiologia , Adulto Jovem
3.
Clin Gastroenterol Hepatol ; 17(13): 2731-2739.e2, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30930275

RESUMO

BACKGROUND & AIMS: Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6-60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy). METHODS: Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC. Archived specimens were retrieved and tested for microsatellite instability (MSI), CpG island methylation, and mutations in KRAS and BRAF. There were 2659 cases of CRC diagnosed within the study window; 6% of these (n = 159) were defined as PCCRCs; 84 of these cases had tissue available and were matched to 84 subjects with detected CRC. RESULTS: Higher proportions of PCCRCs than detected CRCs formed in the proximal colon (64% vs 44%; P = .016) and were of an early stage (86% vs 69%; P = .040). MSI was observed in 32% of PCCRCs compared with 13% of detected CRCs (P = .005). The other molecular features were found in similar proportions of PCCRCs and detected CRCs. In a multivariable logistic regression, MSI (odds ratio, 4.20; 95% CI, 1.58-11.14) was associated with PCCRC. There was no difference in 5-year survival between patients with PCCRCs vs detected CRCs. CONCLUSION: In this population-based cross-sectional study of incident CRC cases in Utah, we found PCCRCs to be more likely to arise in the proximal colon and demonstrate MSI, so PCCRCs and detected CRC appear to have different features or processes of tumorigenesis. Additional studies are needed to determine if post-colonoscopy cancers arise through a specific genetic pathway.


Assuntos
Carcinoma/genética , Colonoscopia , Neoplasias Colorretais/genética , Metilação de DNA , Instabilidade de Microssatélites , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Idoso de 80 Anos ou mais , Carcinogênese , Carcinoma/diagnóstico , Carcinoma/patologia , Estudos de Coortes , Colo Ascendente/patologia , Colo Descendente/patologia , Colo Transverso/patologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Ilhas de CpG , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/diagnóstico , Neoplasias Retais/genética , Neoplasias Retais/patologia , Estudos Retrospectivos , Neoplasias do Colo Sigmoide/diagnóstico , Neoplasias do Colo Sigmoide/genética , Neoplasias do Colo Sigmoide/patologia
4.
Clin Gastroenterol Hepatol ; 17(9): 1807-1813.e1, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30267862

RESUMO

BACKGROUND & AIMS: Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing colorectal cancer (CRC). Although family history of CRC is a well-established risk factor in healthy individuals, its role in patients with IBD is less clear. We aimed to estimate the risk of CRC in a cohort of patients with IBD from Utah and the significance of family history of CRC in a first-degree relative (FDR). METHODS: We identified Utah residents with IBD, using the Intermountain Healthcare and University of Utah Health Sciences databases, from January 1, 1996, through December 31, 2011. CRCs were identified using the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. CRC incidence was compared with that of the state population by standardized incidence ratios (SIRs). RESULTS: A cohort of 9505 individuals with IBD was identified and 101 developed CRC during the study period. The SIR for CRC in patients with Crohn's disease was 3.4 (95% CI, 2.3-4.4), and in patients with ulcerative colitis was 5.2 (95% CI, 3.9-6.6). Patients with IBD and a concurrent diagnosis of primary sclerosing cholangitis had the greatest risk of CRC (SIR, 14.8; 95% CI, 8.3-21.2). A history of CRC in a FDR was associated with a nearly 8-fold increase in risk of CRC in patients with IBD (SIR, 7.9; 95% CI, 1.6-14.3), compared with the state population. CONCLUSIONS: Patients with IBD have a 3- to 5-fold increase in risk of CRC, and those with CRC in a FDR have an almost 8-fold increase in risk. Family history may act as a simple measure to identify individuals with IBD at highest risk for CRC and indicates the need for enhanced surveillance in this population.


Assuntos
Colangite Esclerosante/epidemiologia , Colite Ulcerativa/epidemiologia , Neoplasias Colorretais/epidemiologia , Doença de Crohn/epidemiologia , Anamnese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Risco , Utah/epidemiologia , Adulto Jovem
5.
J Glaucoma ; 27 Suppl 1: S75-S77, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29965901

RESUMO

The Utah Project on Exfoliation Syndrome (UPEXS) study was created to investigate the association between exfoliation syndrome (XFS) and systemic disorders or pathologies. The study utilizes the resources of the Utah Population Database, which is linked to the Utah genealogy, a compilation of large pedigrees extending back 3 to ≥11 generations, representing most families in the state. These family members medical and health records are linked to vital records and can be used effectively to identify familial clustering of disorders, like XFS, with comorbid diseases or health-related data. There is growing evidence that XFS patients have an increased risk for systemic disorders that may reflect the systemic tissue involvement of this disease. Epidemiologic studies of individuals with XFS have reported an increased risk of various pathologies that have abnormalities in extracellular matrix metabolism and repair. For this reason, the UPEXS has focused on disorders that involve the extracellular matrix in general and elastin specifically, such as pelvic organ prolapse, atrial fibrillation, inguinal hernias, and chronic obstructive pulmonary disease. In this paper we present our results from the analysis of pelvic organ prolapse, as well as, preliminary data for atrial fibrillation.


Assuntos
Fibrilação Atrial/epidemiologia , Síndrome de Exfoliação/epidemiologia , Prolapso de Órgão Pélvico/epidemiologia , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Bases de Dados Factuais , Elastina/metabolismo , Síndrome de Exfoliação/metabolismo , Síndrome de Exfoliação/fisiopatologia , Matriz Extracelular/metabolismo , Humanos , Pressão Intraocular/fisiologia , Prolapso de Órgão Pélvico/metabolismo , Prolapso de Órgão Pélvico/fisiopatologia , Utah/epidemiologia
7.
Cancer Causes Control ; 29(2): 193-199, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29243179

RESUMO

PURPOSE: The aim of this study was to determine risk for melanoma among individuals who have a first- or second-degree relative with a history of melanoma, based on the unaffected individual's age and age at diagnosis of the relative. METHODS: The study employed a case-control design using a statewide database linked with a Surveillance Epidemiology and End Results cancer registry. A population-based sample of individuals who received at least one diagnosis of first primary, malignant melanoma (n = 14,281), as well as their first- and second-degree relatives, was included. Control individuals with no history of melanoma (n = 70,889) were matched to cases on birth year, gender, race/ethnicity, and county at birth. RESULTS: Risk for melanoma among relatives of melanoma patients declined with relative's age and age at diagnosis. Individuals between ages 40 and 49 who are first-degree relatives of melanoma patients diagnosed between ages 40 and 49 had the greatest risk for melanoma compared with individuals without a first-degree relative with a melanoma history (HR 4.89; 95% CI 3.11-7.68). Increased melanoma risk among second-degree relatives of patients was typically lower than that for first-degree relatives. CONCLUSIONS: Risk for melanoma, at earlier ages than expected, is increased among relatives of individuals with a history of melanoma, particularly if the melanoma case was diagnosed at a young age. Further research on the relationship between age at diagnosis and relative's melanoma risk could inform melanoma screening recommendations for individuals with a family history of the disease.


Assuntos
Família , Melanoma/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Etnicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fatores de Risco , Adulto Jovem
8.
Clin Exp Rheumatol ; 35 Suppl 106(4): 86-88, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28980899

RESUMO

OBJECTIVES: In systemic sclerosis (SSc) the most common gastrointestinal tract (GIT) complaint is gastroesophageal reflux disease (GERD), which may contribute to oesophagitis, stricture, Barrett's oesophagus, and oesophageal adenocarcinoma. We used a genealogical resource the Utah Population Database (UPDB) to analyse SSc pedigrees for hereditability of oesophageal disease. METHODS: SSc, GERD, oesophagitis, stricture, Barrett's, and oesophageal adenocarcinoma were defined by ICD Ninth and Tenth Revision codes. Familial aggregation, relative risk (RR) of the GIT disease in SSc proband and their relatives was estimated by Cox regression model. The model (adjusted for sex and birth year) was used to evaluate the effects of having or being related to, a case or control for SSc, on GIT diseases. RESULTS: We identified 2,227 unique SSc patients and 11,136 randomly selected controls matched by birth year, gender, and whether born in Utah, in an approximately 1:5 ratio. A SSc proband had a significant high risk of GERD (RR: 3.28), dysphagia (RR 5.58), oesophageal stricture (RR: 5.16), oesophagitis (RR: 4.86), and Barrett's (RR: 4.52) all with significant p-values <2e-16. First-degree relatives of a SSc proband were at elevated risk of GERD (RR: 1.14, p=6.85e-05), dysphagia (RR: 1.22 p=0.002), and oesophagitis (RR: 1.37, p=2.10e-06). First cousins (RR: 1.09, p=0.03) and spouses (RR; 1.37, p=0.02) were at increased risk of esophagitis and dysphagia. CONCLUSIONS: These data suggest that independent of GERD, oesophagitis in SSc patients and their relatives may have both a hereditable and environmental etiology. There does not seem to be a heritable component to Barrett's oesophagus.


Assuntos
Doenças do Esôfago/etiologia , Escleroderma Sistêmico/complicações , Adenocarcinoma/etiologia , Esôfago de Barrett/etiologia , Doenças do Esôfago/genética , Neoplasias Esofágicas/etiologia , Esofagite/etiologia , Refluxo Gastroesofágico/etiologia , Humanos
9.
JAMA Oncol ; 3(12): 1697-1701, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28772302

RESUMO

Importance: The data describing cancer risks associated with Lynch syndrome are variable. Objectives: To quantify the prevalence of families that fulfill the Amsterdam I or II criteria for Lynch syndrome in the Utah population and investigate the risk of colonic and extracolonic cancers in family members and their relatives. Design, Setting, and Participants: In a population-based study, 202 families with Amsterdam I and II criteria­positive pedigrees in the Utah Population Database were identified. Of these, all cancer diagnoses in members of families with Amsterdam criteria and their first-degree, second-degree, and first-cousin relatives were located through linkage to the Utah Cancer Registry. The study was conducted from May 1 to June 30, 2016. Main Outcomes and Measures: Standardized morbidity ratios (SMRs) were estimated by comparing the observed rates of cancer in relatives with population-expected rates estimated internally from the Utah Population Database. Results: A total of 202 families meeting Amsterdam criteria for Lynch syndrome accounted for 2.6% of all colorectal cancers in the state; of these, 59 met both the Amsterdam I and Amsterdam II criteria. Cancers observed in significant excess in the first-degree relatives of Amsterdam criteria pedigrees included colorectal (SMR, 10.10; 95% CI, 9.43-10.81), endometrial (SMR, 5.89; 95% CI, 5.09-6.78), stomach (SMR, 2.90; 95% CI, 2.02-4.03), small intestine (SMR, 7.72; 95% CI, 5.17-11.08), prostate (SMR, 1.94; 95% CI, 1.73-2.17), kidney (SMR, 3.22; 95% CI, 2.45-4.16), urinary bladder (SMR, 1.62; 95% CI, 1.22-2.12), thyroid (SMR, 2.26; 95% CI, 1.55-3.17), and non-Hodgkin lymphoma (SMR, 2.10; 95% CI, 1.64-2.65). Risks of colorectal and endometrial cancers were also found to be elevated in second-degree (SMR, 4.31; 95% CI, 3.98-4.65 and SMR, 2.70; 95% CI, 2.30-3.14, respectively) and first-cousin (SMR, 1.85; 95% CI, 1.70-2.00 and SMR, 1.50; 95% CI, 1.29-1.73, respectively) relatives of families with Amsterdam criteria. Conclusions and Relevance: In this population-based study of cancer risk in families fulfilling the Amsterdam criteria, many of the cancers previously reported to be associated with Lynch syndrome were observed, several previously unreported cancer associations were noted, and the risk of colorectal and endometrial cancer were markedly increased in first-, second-, and even third-degree relatives of these families. This study provides clinicians with population-based, unbiased data to counsel members of families meeting the Amsterdam criteria regarding their elevated risks of cancer and the importance of cancer screening.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias do Endométrio/epidemiologia , Detecção Precoce de Câncer , Família , Feminino , Humanos , Masculino , Linhagem , Prevalência , Estudos Retrospectivos , Medição de Risco , Programa de SEER , Utah/epidemiologia
10.
J Bone Joint Surg Am ; 99(11): 905-913, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28590375

RESUMO

BACKGROUND: It is estimated that the cost to treat periprosthetic joint infection in the United States will approach $1.62 billion by 2020. Thus, the need to better understand the pathogenesis of periprosthetic joint infection is evident. We performed a population-based, retrospective cohort study to determine if familial clustering of periprosthetic joint infection was observed. METHODS: Analyses were conducted using software developed at the Utah Population Database (UPDB) in conjunction with the software package R. The cohort was obtained by querying the UPDB for all patients undergoing total joint arthroplasty and for those patients who had subsequent periprosthetic joint infection. The magnitude of familial risk was estimated by hazard ratios (HRs) from Cox regression models to assess the relative risk of periprosthetic joint infection in relatives and spouses. Using percentiles for age strata, we adjusted for sex, body mass index (BMI) of ≥30 kg/m, and a history of smoking, diabetes, and/or end-stage renal disease. Additionally, we identified families with excess clustering of periprosthetic joint infection above that expected in the population using the familial standardized incidence ratio. RESULTS: A total of 66,985 patients underwent total joint arthroplasty and 1,530 patients (2.3%) had a periprosthetic joint infection. The risk of periprosthetic joint infection following total joint arthroplasty was elevated in first-degree relatives (HR, 2.16 [95% confidence interval (CI), 1.29 to 3.59]) and combined first and second-degree relatives (HR, 1.79 [95% CI, 1.22 to 2.62]). Further, 116 high-risk pedigrees with a familial standardized incidence ratio of >2 and a p value of <0.05 were identified and 9 were selected for genotyping studies based on the observed periprosthetic joint infection/total joint arthroplasty ratio and visual inspection of the pedigrees for lack of excessive comorbidities. CONCLUSIONS: Although preliminary, these data may help to guide further genetic research associated with periprosthetic joint infections. An understanding of familial risks could lead to new discoveries in creating patient-centered pathways for infection prevention in patients at risk. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia de Substituição/efeitos adversos , Saúde da Família/estatística & dados numéricos , Infecções Relacionadas à Prótese/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição/estatística & dados numéricos , Intervalos de Confiança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Software , Cônjuges/estatística & dados numéricos
11.
Int Forum Allergy Rhinol ; 7(6): 591-599, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28272838

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory condition, with significant effects on morbidity and quality of life. Given that other chronic inflammatory conditions have been associated with increased mortality risk, we sought to evaluate the relationship between mortality and CRS including the influence of asthma. Our objective was to determine if CRS, with or without asthma, is associated with altered risk of mortality. METHODS: Using a statewide population database, we retrospectively identified 27,005 patients diagnosed with CRS between 1996 and 2012, and 134,440 unaffected controls matched 5:1 on birth year and sex. Risk of mortality was determined from Cox models and Kaplan-Meier curves were used to compare survival. RESULTS: A significant interaction between CRS and asthma status was observed in which CRS appeared to confer a protective effect in asthma patients. Asthma, when present, increased mortality in CRS-negative controls (p-interaction < 0.0001). Independent of asthma status, CRS patients exhibited a decreased mortality risk (hazard ratio [HR] = 0.80; 95% confidence interval [CI], 0.74 to 0.85) compared to controls. However, in patients diagnosed at or before the median age of CRS onset (42 years) independent of asthma status, survival was not improved (HR = 0.98; 95% CI, 0.81 to 1.18). Risk of mortality was greater in CRS with nasal polyps (n = 1643) compared to 25,362 polyp-negative CRS patients (HR = 1.38; 95% CI, 1.09 to 1.77). CONCLUSION: CRS was associated with lower risk of mortality compared to controls, and appeared to mitigate increased mortality from asthma. We posit that better survival conferred by CRS may be secondary to treatment. However, the etiology of this relationship and the effect of CRS treatment on mortality are unknown.


Assuntos
Asma/mortalidade , Rinite/mortalidade , Sinusite/mortalidade , Adolescente , Adulto , Doença Crônica , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco , Utah/epidemiologia , Adulto Jovem
12.
J Allergy Clin Immunol ; 140(4): 1138-1143, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28192145

RESUMO

BACKGROUND: Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors. OBJECTIVE: This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives. METHODS: The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls. RESULTS: There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed <18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE. CONCLUSIONS: This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives.


Assuntos
Esofagite Eosinofílica/genética , Família , Família Multigênica , Linhagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Interação Gene-Ambiente , Genealogia e Heráldica , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Família Multigênica/genética , Polimorfismo Genético , Grupos Populacionais , Risco , Utah , Adulto Jovem
13.
Dig Dis Sci ; 62(8): 2126-2132, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28050782

RESUMO

BACKGROUND AND AIMS: The molecular, endoscopic, and histological features of IBD-associated CRC differ from sporadic CRC. The objective of this study was to describe the prevalence, clinical features, and prognosis of IBD-associated CRC compared to patients with sporadic CRC in a US statewide population-based cohort. METHODS: All newly diagnosed cases of CRC between 1996 and 2011 were obtained from Utah Cancer Registry. IBD was identified using a previously validated algorithm, from statewide databases of Intermountain Healthcare, University of Utah Health Sciences, and the Utah Population Database. Logistic regression was performed to identify risk factors associated with IBD-associated cancer and Cox regression for differences in survival. RESULTS: Among 12,578 patients diagnosed with CRC, 101 (0.8%) had a prior history of IBD (61 ulcerative colitis and 40 Crohn's disease). The mean age at CRC diagnosis was greater for patients without IBD than those with IBD (67.1 vs 52.8 years, P < 0.001). Individuals with IBD-associated CRC were more likely to be men (odds ratio [OR] 1.90, 95% CI 1.23-2.92), aged less than 65 years (OR 6.77, 95% CI 4.06-11.27), and have CRC located in the proximal colon (OR 2.79, 95% CI 1.85-4.20) than those with sporadic CRC. Nearly 20% of the IBD-associated CRCs had evidence of primary sclerosing cholangitis. After adjustment for age, gender, and stage at diagnosis, the excess hazard of death after CRC diagnosis was 1.7 times higher in IBD than in non-IBD patients (95% CI 1.27-2.33). CONCLUSIONS: The features of patients with CRC and IBD differ significantly from those without IBD and may be associated with increased mortality.


Assuntos
Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Doença de Crohn/complicações , Adulto , Fatores Etários , Idade de Início , Idoso , Colangite Esclerosante/complicações , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/patologia , Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Doença de Crohn/epidemiologia , Doença de Crohn/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Utah/epidemiologia
14.
Dig Dis Sci ; 61(12): 3627-3632, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27655103

RESUMO

BACKGROUND AND OBJECTIVES: Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second-degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite. METHODS: BTC diagnosed between 1980 and 2011 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and gender-matched BTC-free controls were selected to form the comparison group for determining BTC risk in relatives using Cox regression analysis. RESULTS: Of the 1302 index patients diagnosed with BTC, 550 (42.2 %) were located in the gallbladder and 752 (57.8 %) were cholangiocarcinomas. There was no elevated risk of BTC (all subsites combined) in FDRs (HR 0.94, 95 % CI 0.29-3.0), SDRs (HR 0.25, 95 % CI 0.06-1.03), and FCs (HR 0.96, 95 % CI 0.61-1.51) of BTC cases compared to cancer-free controls. Similarly, no increased familial risk of GBC or CC was found in relatives of BTC patients stratified by tumor subsite compared to relatives of controls. CONCLUSIONS: Relatives of BTC patients are not at an increased risk of GBC or CC in a statewide population. This suggests that biliary tract cancer risk is not associated with a familial predisposition and may be mitigated more strongly by environmental modifiers.


Assuntos
Adenocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Família , Neoplasias da Vesícula Biliar/genética , Linhagem , Sistema de Registros , Adenocarcinoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/epidemiologia , Ductos Biliares Extra-Hepáticos , Ductos Biliares Intra-Hepáticos , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/genética , Colangiocarcinoma/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Utah/epidemiologia , Adulto Jovem
15.
Am J Gastroenterol ; 111(7): 926-32, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27215923

RESUMO

OBJECTIVES: Recent genome-wide association studies have suggested possible genetic associations between eosinophilic esophagitis (EoE) and genes associated with autoimmunity. No studies to date have looked at potential genetic association of EoE with specific autoimmune diseases by evaluating such diagnoses within family members. Investigate the risk of specific autoimmune disease within EoE probands and their extended family members. METHODS: The Utah Population Database offers a unique opportunity to link medical records from over 85% of Utah's population to genealogy records representing Utah. We searched for associations of specific autoimmune diseases in probands diagnosed with EoE and their extended family members (e.g., first cousins). Comparisons were made to age- and sex-matched controls and their respective families at a 5:1 ratio. RESULTS: Excess risk for multiple autoimmune conditions was detected in subjects with a diagnosis of EoE. Celiac, Crohn's, ulcerative colitis (UC), rheumatoid arthritis, IgA deficiency, CVID, multiple sclerosis (MS), and Hashimoto's thyroiditis were found at increased risk in first-degree relatives of EoE subjects. UC, systemic sclerosis, and MS had nominally significant associations within second-degree family members of EoE subjects; and, in reverse analysis, probands and their families with the above three conditions were at an increased risk for EoE suggesting shared genetic factors with EoE. CONCLUSIONS: Patients with EoE have an increased risk of multiple autoimmune diseases. Possible shared genetic etiologies were observed between EoE and UC, systemic sclerosis, and MS. Practitioners should be aware of these comorbid associations and query all EoE patients and family members for symptoms of these diseases.


Assuntos
Doenças Autoimunes , Autoimunidade/genética , Esofagite Eosinofílica , Linhagem , Adolescente , Adulto , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Pré-Escolar , Comorbidade , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/etiologia , Esofagite Eosinofílica/imunologia , Família , Estudo de Associação Genômica Ampla , Humanos , Registros Médicos Orientados a Problemas/estatística & dados numéricos , Distribuição Aleatória , Projetos de Pesquisa , Fatores de Risco , Utah/epidemiologia
16.
JAMA Oncol ; 2(3): 340-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26863281

RESUMO

IMPORTANCE: Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all cancers and is associated with poor prognosis. Familial clustering of different cancer sites with CUP is unknown and may provide information regarding etiology, as well as elevated cancer risks in relatives. OBJECTIVE: To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of patients who received a diagnosis of CUP between 1980 and 2010 identified from the Utah Cancer Registry. Population controls with no CUP diagnosis were sex and age matched 10:1 to patients with CUP. Data about relatives were drawn from the Utah Population Database. MAIN OUTCOMES AND MEASURES: Familial aggregation of cancer risk in relatives of cases compared with controls using Cox regression analysis. RESULTS: For the 4160 index patients (median [interquartile range] age, 72 [62-81] years; 47.6% male) who had received a diagnosis of CUP, first-degree relatives were at an elevated risk of CUP themselves (hazard ratio [HR], 1.35 [95% CI, 1.07-1.70]), as well as lung (HR, 1.37 [95% CI, 1.22-1.54]), pancreatic (HR, 1.28 [95% CI, 1.06-1.54]), myeloma (HR, 1.28 [95% CI, 1.01-1.62]), and non-Hodgkin lymphoma (HR, 1.16 [95% CI, >1.00-1.35]) cancers compared with controls without CUP. When the analysis was restricted to relatives of cancer-free controls, additional increased risks for colon (HR, 1.19 [95% CI, 1.06-1.33]) and bladder (HR, 1.18 [95% CI, >1.00-1.38]) cancers were observed. Second-degree relatives of patients with CUP were at a slight increased risk of lung (HR, 1.14 [95% CI, 1.03-1.26]), pancreatic (HR, 1.17 [95% CI, 1.01-1.37]), breast (HR, 1.09 [95% CI, 1.02-1.16]), melanoma (HR, 1.09 [95% CI, >1.00-1.19]), and ovarian (HR, 1.19 [95% CI, 1.02-1.39]) cancers. CONCLUSIONS AND RELEVANCE: Relatives of patients with CUP are at increased risk of CUP and several other malignant neoplasms, including lung, pancreatic, and colon cancer. The present data may suggest sites of origin for CUP and provide cancer risk information for relatives of patients with CUP that can lead to effective intervention. Relatives of patients with CUP should be aware of the elevated risks for lung, pancreatic, and colon cancer and encouraged to modify risk factors and adhere to site-specific population cancer screening.


Assuntos
Predisposição Genética para Doença , Neoplasias Primárias Desconhecidas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias do Colo/genética , Família , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Linfoma não Hodgkin/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Utah
17.
Laryngoscope ; 126(3): 739-45, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26228920

RESUMO

OBJECTIVES/HYPOTHESIS: To determine the risk of chronic rhinosinusitis (CRS) in relatives of children with a diagnosis of CRS. STUDY DESIGN: Retrospective observational cohort study with population-based matched controls. METHODS: A unique genealogical database linked to medical records was used to identify subjects ≤12 years old with a diagnosis of CRS from 1996 to 2011. The familial recurrence risks of CRS in first- through fifth-degree relatives of probands were calculated using Cox models and compared to controls randomly selected from the Utah population and matched 10:1 on sex and birth year. RESULTS: We identified 496 pediatric patients with CRS. Siblings of patients with CRS demonstrated a 57.5-fold increased risk (P < 10(-8) ) of also having pediatric CRS. First cousins had a 9.0-fold increased risk (P < 10(-3) ) and second cousins had a 2.9-fold increased risk (P = .002) of pediatric CRS. First-degree relatives, second-degree relatives, and first cousins of pediatric cases demonstrated a significant increased risk of having adult CRS. Parents of probands demonstrated a 5.6-fold increased risk (P < 10(-15) ). Fifty-five probands had one affected parent versus three probands with two affected parents. CONCLUSIONS: In the largest population study to date of children with CRS, a significant familial risk is confirmed. Parents of probands were also at increased risk, although it was much more likely for one parent to be affected than both, suggesting a genetic component of the disease. Further understanding of the genetic basis of CRS and its interplay with environmental factors could clarify the etiology and lead to more effective targeted treatments. LEVEL OF EVIDENCE: 3b Laryngoscope, 126:739-745, 2016.


Assuntos
Predisposição Genética para Doença/epidemiologia , Linhagem , Rinite/genética , Sinusite/genética , Adolescente , Distribuição por Idade , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Rinite/epidemiologia , Rinite/fisiopatologia , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Sinusite/epidemiologia , Sinusite/fisiopatologia
18.
Clin Gastroenterol Hepatol ; 13(13): 2305-11.e1-2, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26188136

RESUMO

BACKGROUND & AIMS: It is not clear whether familial risk of colorectal cancer (CRC) varies with age of index CRC patients or their relatives. We quantified the risk of CRC in first-degree relatives (FDRs), second-degree relatives, and first-cousin relatives of individuals with CRC, stratified by ages and sexes of index patients and ages of relatives. METHODS: CRCs diagnosed between 1980 and 2010 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and sex-matched CRC-free individuals were selected to form the comparison group. CRC risk in relatives was determined by Cox regression analysis. RESULTS: Of 18,208 index patients diagnosed with CRC, the highest familial risk was observed in FDRs of index CRC patients who were diagnosed at an age younger than 40 years (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.7-3.79). However, familial risk was increased in FDRs even when the index case was diagnosed with cancer at an advanced age (>80 years; HR, 1.76; 95% CI, 1.59-1.94). Ages of relatives and ages of index cases of CRC each affected familial cancer risk; the highest risk was found in young relatives (<50 years) of individuals with early-onset CRC (<40 years; HR, 7.0; 95% CI, 2.86-17.09). CONCLUSIONS: All relatives of individuals with CRC are at increased risk for this cancer, regardless of the age of diagnosis of the index patient. Although risk is greatest among young relatives of early-onset CRC cases, relatives of patients diagnosed at advanced ages also have an increased risk.


Assuntos
Neoplasias Colorretais/epidemiologia , Saúde da Família , Família , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Utah/epidemiologia , Adulto Jovem
19.
Arthritis Care Res (Hoboken) ; 67(2): 310-2, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24757045

RESUMO

OBJECTIVE: To examine parental influence on the development of systemic sclerosis (SSc; scleroderma). We designed 3 studies: mitochondrial inheritance, birth order (a possible surrogate marker for microchimerism), and paternal age at conception (a possible surrogate for telomere erosion) to examine their association with development of SSc. METHODS: SSc was defined by International Classification of Diseases, Ninth and Tenth Revision codes (ICD-9 710.1 and ICD 10 M34.0, M34.1, and M34.9) and identified from statewide discharge data, University of Utah Health Science Center Enterprise Data Warehouse (UUHSC), and death certificates that were linked to the Utah Population Database (UPDB) for analysis. Mitochondrial inheritance was evaluated by conditional logistic regression and population attributable risk using familial standardized incidence ratio as the covariate. Chi-square test and logistic regression were used to evaluate birth order and maternal/paternal age at conception of the SSc proband. RESULTS: We found 1,947 unique SSc patients from UUHSC and UPDB. We selected 5 controls per case (n = 9,115), matched by birth year and sex. Mitochondrial inheritance analysis indicated no evidence to suggest SSc was associated with mitochondrial inheritance. Birth order and maternal/paternal age at conception analysis results show that they also do not significantly affect SSc development. CONCLUSION: Results suggest that although heritable risk of SSc is observed, mitochondrial inheritance, birth order, and parental age are not likely responsible for pathogenesis.


Assuntos
Ordem de Nascimento , Pais , Escleroderma Sistêmico/genética , Adolescente , Adulto , DNA Mitocondrial/análise , DNA Mitocondrial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Gastroenterology ; 147(4): 814-821.e5; quiz e15-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25042087

RESUMO

BACKGROUND & AIMS: Colorectal cancer (CRC) frequently develops in multiple members of the same families, but more data are needed to prepare effective screening guidelines. We quantified the risk of CRC and adenomas in first-degree relatives (FDRs) and second-degree relatives and first cousins of individuals with CRC, and stratified risk based on age at cancer diagnosis. METHODS: We performed a case-control study of Utah residents, 50-80 years old, who underwent colonoscopy from 1995 through 2009. Index cases (exposed to colonoscopy) were colonoscopy patients with a CRC diagnosis. Age- and sex-matched individuals, unexposed to colonoscopy (controls) were selected to form the comparison groups for determining risk in relatives. Colonoscopy results were linked to cancer and pedigree information from the Utah Population Database to investigate familial aggregation of colorectal neoplasia using Cox regression analysis. RESULTS: Of 126,936 patients who underwent a colonoscopy, 3804 were diagnosed with CRC and defined the index cases. FDRs had an increased risk of CRC (hazard rate ratio [HRR], 1.79; 95% confidence interval [CI],1.59-2.03), as did second-degree relatives (HRR, 1.32; 95% CI, 1.19-1.47) and first cousins (HRR, 1.15; 95% CI, 1.07-1.25), compared with relatives of controls. This risk was greater for FDRs when index patients developed CRC at younger than age 60 years (HRR, 2.11; 95% CI, 1.70-2.63), compared with older than age 60 years (HRR, 1.77; 95% CI, 1.58-1.99). The risk of adenomas (HRR, 1.82; 95% CI, 1.66-2.00) and adenomas with villous histology (HRR, 2.43; 95% CI, 1.96-3.01) also were increased in FDRs. Three percent of CRCs in FDRs would have been missed if the current guidelines, which stratify screening recommendations by the age of the proband, were strictly followed. CONCLUSIONS: FDRs, second-degree relatives, and first cousins of patients who undergo colonoscopy and are found to have CRC have a significant increase in the risk of colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and families.


Assuntos
Adenoma/epidemiologia , Adenoma/genética , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Linhagem , Adenoma/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores Sexuais , Utah/epidemiologia
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