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1.
Radiology ; 307(2): e212915, 2023 04.
Article in English | MEDLINE | ID: mdl-36625743

ABSTRACT

Background To the knowledge of the authors, no strong evidence supports surveillance imaging in patients with head and neck cancer (HNC). Purpose To investigate the association between surveillance imaging and mortality using a population-based study design with statewide cancer registry data, all-payer claims data, and health care facility data. Materials and Methods The retrospective population-based study identified patients with HNC diagnosed between January 2012 and December 2017. Current Procedural Terminology codes were used to search surveillance imaging procedures. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for mortality with adjustment for sex, ethnicity, age, health insurance status, cancer site, stage, and treatment. Results The study identified 1004 patients (mean age, 61 years ± 12 [SD]; 753 men), including 902 patients with squamous cell carcinoma (SCC) HNC and 102 patients with non-SCC. The effect of imaging on mortality among patients with SCC was not statistically significant when the entire sample was analyzed (HR, 0.76; 95% CI: 0.57, 1.02; P = .07). However, in stratified analyses by cancer stage, surveillance imaging was associated with lower mortality among patients with SCC for regionalized cancer stage (HR, 0.55; 95% CI: 0.36, 0.83; P = .005) and distant cancer stage (HR, 0.40; 95% CI: 0.19, 0.83; P = .01). Among patients with non-SCC, surveillance imaging was associated with lower mortality versus no surveillance imaging (HR, 0.19; 95% CI: 0.04, 0.94; P = .04). PET/CT was associated with lower mortality for patients with SCC (HR, 0.29; 95% CI: 0.09, 0.94; P = .04), and CT and/or MRI was associated with lower mortality for patients with non-SCC (HR, 0.11; 95% CI: 0.01, 0.94; P = .04). Conclusion Surveillance imaging was associated with lower mortality among patients with head and neck squamous cell carcinoma with regionalized or distant disease. The surveillance imaging protective association was observed up to 2 years after treatment completion. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Branstetter in this issue.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Male , Humans , Middle Aged , Positron Emission Tomography Computed Tomography , Retrospective Studies , Head and Neck Neoplasms/diagnostic imaging , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Magnetic Resonance Imaging/methods
2.
Cancer Causes Control ; 34(2): 171-180, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36414860

ABSTRACT

PURPOSE: It is unknown whether cancer treatment contributes more to long-term disease risk than lifestyle factors and comorbidities among B-cell non-Hodgkin lymphoma (B-NHL) survivors. METHODS: B-NHL survivors were identified in the Utah Cancer Registry from 1997 to 2015. Population attributable fractions (PAF) were calculated to assess the role of clinical and lifestyle factors for six cardiovascular, pulmonary, and renal diseases. RESULTS: Cancer treatment contributed to 11% of heart and pulmonary conditions and 14.1% of chronic kidney disease. Charlson Comorbidity Index (CCI) at baseline contributed to all six diseases with a range of 9.9% of heart disease to 26.5% of chronic kidney disease. High BMI at baseline contributed to 18.4% of congestive heart failure and 7.9% of pneumonia, while smoking contributed to 4.8% of COPD risk. CONCLUSION: Cancer treatment contributed more to heart disease, COPD, and chronic kidney disease than lifestyle factors and comorbidities among B-NHL survivors. High BMI at baseline contributed more to congestive heart failure and pneumonia than cancer treatment, whereas smoking at baseline was not a major contributor in this B-NHL survivor cohort. Baseline comorbidities consistently demonstrated high attributable risks for these diseases, demonstrating a strong association between preexisting comorbidities and aging-related disease risks.


Subject(s)
Heart Failure , Lymphoma, Non-Hodgkin , Pulmonary Disease, Chronic Obstructive , Renal Insufficiency, Chronic , Humans , Lymphoma, Non-Hodgkin/epidemiology , Survivors , Comorbidity , Obesity/complications , Obesity/epidemiology , Heart Failure/complications , Heart Failure/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/complications , Aging , Pulmonary Disease, Chronic Obstructive/epidemiology , Risk Factors
3.
J Neurosurg ; 139(1): 266-274, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-36433874

ABSTRACT

OBJECTIVE: Inherited variants predisposing patients to type 1 or 1.5 Chiari malformation (CM) have been hypothesized but have proven difficult to confirm. The authors used a unique high-risk pedigree population resource and approach to identify rare candidate variants that likely predispose individuals to CM and protein structure prediction tools to identify pathogenicity mechanisms. METHODS: By using the Utah Population Database, the authors identified pedigrees with significantly increased numbers of members with CM diagnosis. From a separate DNA biorepository of 451 samples from CM patients and families, 32 CM patients belonging to 1 or more of 24 high-risk Chiari pedigrees were identified. Two high-risk pedigrees had 3 CM-affected relatives, and 22 pedigrees had 2 CM-affected relatives. To identify rare candidate predisposition gene variants, whole-exome sequence data from these 32 CM patients belonging to 24 CM-affected related pairs from high-risk pedigrees were analyzed. The I-TASSER package for protein structure prediction was used to predict the structures of both the wild-type and mutant proteins found here. RESULTS: Sequence analysis of the 24 affected relative pairs identified 38 rare candidate Chiari predisposition gene variants that were shared by at least 1 CM-affected pair from a high-risk pedigree. The authors found a candidate variant in HOXC4 that was shared by 2 CM-affected patients in 2 independent pedigrees. All 4 of these CM cases, 2 in each pedigree, exhibited a specific craniocervical bony phenotype defined by a clivoaxial angle less than 125°. The protein structure prediction results suggested that the mutation considered here may reduce the binding affinity of HOXC4 to DNA. CONCLUSIONS: Analysis of unique and powerful Utah genetic resources allowed identification of 38 strong candidate CM predisposition gene variants. These variants should be pursued in independent populations. One of the candidates, a rare HOXC4 variant, was identified in 2 high-risk CM pedigrees, with this variant possibly predisposing patients to a Chiari phenotype with craniocervical kyphosis.


Subject(s)
Brain , Genetic Predisposition to Disease , Homeodomain Proteins , Humans , Genetic Predisposition to Disease/genetics , Genotype , Homeodomain Proteins/genetics , Mutation , Pedigree , Phenotype , Risk Factors , Brain/abnormalities
4.
Cancer Med ; 12(2): 1801-1812, 2023 01.
Article in English | MEDLINE | ID: mdl-35773781

ABSTRACT

BACKGROUND: Ovarian cancer is the fifth most common female cancer in the United States. There have been very few studies investigating mental health diagnoses among ovarian cancer survivors with long-term follow up. The aim of this study is to examine the incidence of mental illness among ovarian cancer survivors compared to a general population cohort. A secondary aim is to investigate risk factors for mental illnesses among ovarian cancer survivors. PATIENTS AND METHODS: Cohorts of 1689 ovarian cancer patients diagnosed between 1996 and 2012 and 7038 women without cancer matched by age and birth state from the general population were identified. Mental health diagnoses were identified from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios (HRs). RESULTS: Ovarian cancer survivors experienced increased risks of mental illnesses within the first 2 years after cancer diagnosis (HR = 3.55, 95% CI = 3.04-4.14). The risks of depression among ovarian cancer survivors were nearly 3-fold within the first 2 years of cancer diagnosis (HR = 2.59, 95% CI = 1.94-3.47), and 1.69-fold at 2-5 years after cancer diagnosis (HR = 1.69, 95% CI = 1.18-2.42). Ovarian cancer survivors experienced an 80% increased risk of death with a mental illness diagnosis (HR = 1.80, 95% CI = 1.48-2.18) and a 94% increased risk of death with a depression diagnosis (HR = 1.94, 95% CI = 1.56-2.40). CONCLUSIONS: Higher risks of mental illnesses were observed among ovarian cancer survivors throughout the follow-up periods of 0-2 years and 2-5 years after cancer diagnosis. Multidisciplinary care is needed to monitor and treat mental illnesses among ovarian cancer survivors.


Subject(s)
Cancer Survivors , Mental Disorders , Ovarian Neoplasms , Humans , Female , United States/epidemiology , Mental Health , Survivors/psychology , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/complications , Risk Factors , Mental Disorders/epidemiology , Mental Disorders/etiology
5.
Article in English | MEDLINE | ID: mdl-36554301

ABSTRACT

(1) Importance: Alzheimer's disease (AD) is complex and only partially understood. Analyzing the relationship between other more treatable or preventable diseases and AD may help in the prevention and the eventual development of treatments for AD. Risk estimation in a high-risk population, rather than a population already affected with AD, may reduce some bias in risk estimates. (2) Objective: To examine the rates of various comorbidities and cancers in individuals at high-risk for AD, but without a clinical diagnosis, relative to individuals from the same population with normal AD risk. (3) Design, Setting, and Participants: We conducted a study using data from the Utah Population Database (UPDB). The UPDB contains linked data from the Utah Cancer Registry, Utah death certificates, the Intermountain Health patient population, and the University of Utah Health patient population. Subjects were selected based on the availability of ancestral data, linked health information, and self-reported biometrics. (4) Results: In total, 75,877 participants who were estimated to be at high risk for AD based on family history, but who did not have an active AD diagnosis, were analyzed. A lower incidence of diabetes (RR = 0.95, 95% CI [0.92,0.97], p < 0.001), hypertension (RR = 0.97, 95% CI [0.95,0.99], p < 0.001), and heart disease (RR = 0.95, 95% CI [0.93,0.98], p < 0.001) was found. There was no difference in rates of cerebrovascular disease or other forms of dementia. Of the 15 types of cancer analyzed: breast (RR = 1.23, 95% CI [1.16, 1.30], p < 0.001); colorectal (RR = 1.30, 95% CI [1.21, 1.39], p < 0.001); kidney (RR = 1.49, 95% CI (1.29, 1.72), p < 0.001); lung (RR = 1.25, 95% CI [1.13, 1.37], p < 0.001); non-Hodgkin's Lymphoma (RR = 1.29, 95% CI [1.15, 1.44], p < 0.001); pancreas (RR = 1.34, 95% CI [1.16, 1.55], p < 0.001); stomach (RR = 1.59, 95% CI [1.36, 1.86], p < 0.001); and bladder (RR = 1.40, 95% CI [1.25, 1.56], p < 0.001), cancers were observed in significant excess among individuals at high-risk for AD after correction for multiple testing. (5) Conclusions and Relevance: Since age is the greatest risk factor for the development of AD, individuals who reach more advanced ages are at increased risk of developing AD. Consistent with this, people with fewer comorbidities earlier in life are more likely to reach an age where AD becomes a larger risk. Our findings show that individuals at high risk for AD have a decreased incidence of various other diseases. This is further supported by our finding that our high-risk group was also found to have an increased incidence of various cancers, which also increase in risk with age. There is the possibility that a more meaningful or etiological relationship exists among these various comorbidities. Further research into the etiological relationship between AD and these comorbidities may elucidate these possible interactions.


Subject(s)
Alzheimer Disease , Neoplasms , Humans , Alzheimer Disease/epidemiology , Neoplasms/epidemiology , Comorbidity , Incidence , Risk Factors
6.
Support Care Cancer ; 31(1): 51, 2022 Dec 17.
Article in English | MEDLINE | ID: mdl-36526929

ABSTRACT

Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HRRegional vs. Localized: 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.


Subject(s)
Cancer Survivors , Genital Neoplasms, Female , Sexual Dysfunction, Physiological , Female , Humans , Cohort Studies , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiology , Genital Neoplasms, Female/complications , Survivors
7.
Cancer ; 128(19): 3564-3572, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35916651

ABSTRACT

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.


Subject(s)
Hodgkin Disease , Mental Disorders , Hodgkin Disease/complications , Hodgkin Disease/epidemiology , Hodgkin Disease/pathology , Humans , Mental Disorders/complications , Mental Disorders/epidemiology , Mental Health , Risk Factors , Survival Rate
8.
Cancer ; 128(14): 2826-2835, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35561317

ABSTRACT

BACKGROUND: Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. METHODS: A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. RESULTS: Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. CONCLUSION: Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.


Subject(s)
Breast Neoplasms , Cancer Survivors , Cardiovascular Diseases , Breast Neoplasms/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Female , Humans , Proportional Hazards Models , Risk Factors
9.
Cancer Epidemiol Biomarkers Prev ; 30(12): 2268-2277, 2021 12.
Article in English | MEDLINE | ID: mdl-34732401

ABSTRACT

BACKGROUND: Younger cancer survivors may develop age-related diseases due to the cancer treatment that they undergo. The aim of this population-based study is to estimate incidence of age-related diseases besides cardiovascular disease among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. METHODS: Survivors of B-NHL were diagnosed between 1997 and 2015 from the Utah Cancer Registry. Using the Utah Population Database, up to 5 cancer-free individuals from the general population were matched with a B-NHL survivor on sex, birth year, and state of birth. Hazard ratios (HR) for age-related disease outcomes, which were identified from medical records and statewide health care facility data, were estimated using Cox Proportional Hazards models for B-NHL survivors diagnosed at <65 years versus ≥65 years at least 5 years since B-NHL diagnosis. RESULTS: Comparing 2,129 B-NHL survivors with 8,969 individuals from the general population, younger B-NHL survivors had higher relative risks of acute renal failure [HR, 2.24; 99% confidence interval (CI), 1.48-3.39; P heterogeneity = 0.017), pneumonia (HR, 2.42; 99% CI, 1.68-3.49; P heterogeneity = 0.055), and nutritional deficiencies (HR, 2.08; 99% CI, 1.48-2.92; P heterogeneity = 0.051) ≥5 years after cancer diagnosis. CONCLUSION: Younger B-NHL survivors had higher relative risks of acute renal failure, pneumonia, and nutritional deficiencies than older B-NHL survivors compared with their respective general population cohorts, ≥5 years after cancer diagnosis.


Subject(s)
Cancer Survivors/statistics & numerical data , Lymphoma, B-Cell/therapy , Outcome Assessment, Health Care/statistics & numerical data , Adult , Aged , Aged, 80 and over , Aging , Chronic Disease/epidemiology , Female , Humans , Lymphoma, B-Cell/epidemiology , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Assessment
10.
Cancer Med ; 10(12): 4117-4126, 2021 06.
Article in English | MEDLINE | ID: mdl-33979029

ABSTRACT

INTRODUCTION: Young cancer survivors may be at increased risk of early-onset chronic health conditions. The aim of this population-based study is to estimate cardiovascular disease (CVD) risk among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. METHODS: B-NHL survivors diagnosed from 1997 to 2015 in the Utah Cancer Registry were matched with up to five cancer-free individuals on birth year, sex, and birth state, using the statewide Utah Population Database. Electronic medical records and statewide health care facility data were used to identify disease outcomes ≥5 years after cancer diagnosis. Cox Proportional Hazards models were used to estimate hazard ratios for B-NHL survivors diagnosed at <65 years and ≥65 years old. RESULTS: Younger B-NHL survivors had higher relative risks than older cancer survivors of chronic rheumatic disease of the heart valves (HR = 4.14, 99% CI = 2.17-7.89; P valueheterogeneity = 0.004); peri-, endo-, and myocarditis (HR = 2.43, 99% CI = 1.38-4.28; P valueheterogeneity = 0.016); diseases of the arteries (HR = 1.63, 99% CI = 1.21-2.21; P valueheterogeneity = 0.044); and hypotension (HR = 2.44, 99% CI = 1.58-3.75; P valueheterogeneity = 0.048). B-NHL survivors of both age groups had elevated relative risks of heart disease overall and congestive heart failure. CONCLUSION: Younger B-NHL survivors had higher risks than older B-NHL survivors of specific cardiovascular diseases compared to their respective general population cohorts.


Subject(s)
Cancer Survivors , Cardiovascular Diseases/etiology , Heart Disease Risk Factors , Lymphoma, B-Cell/complications , Adult , Age Factors , Aged , Aged, 80 and over , Female , Heart Diseases/etiology , Heart Failure/etiology , Heart Valve Diseases/etiology , Humans , Hypotension/etiology , Male , Middle Aged , Myocarditis/etiology , Proportional Hazards Models , Registries , Rheumatic Heart Disease/etiology , Utah , Vascular Diseases/etiology , Young Adult
11.
JNCI Cancer Spectr ; 5(2)2021 04.
Article in English | MEDLINE | ID: mdl-33889806

ABSTRACT

Background: Breast cancer is the leading cause of cancer death among Hispanic women. The aim of our study was to estimate cardiovascular disease (CVD) risk among Hispanic and non-Hispanic White (NHW) breast cancer survivors compared with their respective general population cohorts. Methods: Cohorts of 17 469 breast cancer survivors (1774 Hispanic and 15 695 NHW) in the Utah Cancer Registry diagnosed between 1997 and 2016, and 65 866 women (6209 Hispanic and 59 657 NHW) from the general population in the Utah Population Database were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CVD. Results: The risk of diseases of the circulatory system was higher in Hispanic than NHW breast cancer survivors 1-5 years after cancer diagnosis, in comparison with their respective general population cohorts (HRHispanic = 1.94, 99% confidence interval [CI] = 1.49 to 2.53; HNHW = 1.38, 99% CI = 1.33 to 1.43; 2-sided P heterogeneity = .01, respectively). Increased risks were observed for both Hispanic and NHW breast cancer survivors for diseases of the heart and the veins and lymphatics, compared with the general population cohorts. More than 5 years after cancer diagnosis, elevated risk of diseases of the veins and lymphatics persisted in both ethnicities. The CVD risk due to chemotherapy and hormone therapy was higher in Hispanic than NHW breast cancer survivors but did not differ for distant stage, higher baseline comorbidities, or baseline smoking. Conclusions: We observed a risk difference for diseases of the circulatory system between Hispanic and NHW breast cancer survivors compared with their respective general population cohorts but only within the first 5 years of cancer diagnosis.


Subject(s)
Breast Neoplasms/ethnology , Cancer Survivors , Cardiovascular Diseases/ethnology , Hispanic or Latino , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Cancer Survivors/statistics & numerical data , Cardiovascular Diseases/etiology , Cohort Studies , Confidence Intervals , Female , Hispanic or Latino/statistics & numerical data , Humans , Lymphatic Diseases/ethnology , Lymphatic Diseases/etiology , Middle Aged , Proportional Hazards Models , Registries , Risk Factors , Time Factors , Utah , White People/statistics & numerical data , Young Adult
12.
Neuro Oncol ; 23(2): 277-283, 2021 02 25.
Article in English | MEDLINE | ID: mdl-32644145

ABSTRACT

BACKGROUND: There is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside. METHODS: Genome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Access to formalin-fixed paraffin embedded tissue samples archived in a biorepository allowed analysis of extended pedigrees. RESULTS: Individual high-risk pedigrees were singly informative for linkage at multiple regions. Suggestive evidence for linkage was observed on chromosomes 2, 3, 14, and 16. The chromosome 16 region in particular contains a promising candidate gene, pyridoxal-dependent decarboxylase domain-containing 1 (PDXDC1), with prior evidence for involvement with glioblastoma from other previously reported experimental settings, and contains the lead single nucleotide polymorphism (rs3198697) from the linkage analysis of the chromosome 16 region. CONCLUSIONS: Pedigrees with a statistical excess of primary brain cancers have been identified in a unique genealogy resource representing the homogeneous Utah population. Genome-wide linkage analysis of these pedigrees has identified a potential candidate predisposition gene, as well as multiple candidate regions that could harbor predisposition loci, and for which further analysis is suggested.


Subject(s)
Brain Neoplasms , Pyridoxal , Brain Neoplasms/genetics , Genetic Predisposition to Disease , Humans , Pedigree , Utah
13.
Ann Hum Genet ; 85(2): 58-72, 2021 03.
Article in English | MEDLINE | ID: mdl-33026655

ABSTRACT

Osteoporosis is a common skeletal disorder characterized by deterioration of bone tissue. The set of genetic factors contributing to osteoporosis is not completely specified. High-risk osteoporosis pedigrees were analyzed to identify genes that may confer susceptibility to disease. Candidate predisposition variants were identified initially by whole exome sequencing of affected-relative pairs, approximately cousins, from 10 pedigrees. Variants were filtered on the basis of population frequency, concordance between pairs of cousins, affecting a gene associated with osteoporosis, and likelihood to have functionally damaging, pathogenic consequences. Subsequently, variants were tested for segregation in 68 additional relatives of the index carriers. A rare variant in MEGF6 (rs755467862) showed strong evidence of segregation with the disease phenotype. Predicted protein folding indicated the variant (Cys200Tyr) may disrupt structure of an EGF-like calcium-binding domain of MEGF6. Functional analyses demonstrated that complete loss of the paralogous genes megf6a and megf6b in zebrafish resulted in significant delay of cartilage and bone formation. Segregation analyses, in silico protein structure modeling, and functional assays support a role for MEGF6 in predisposition to osteoporosis.


Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Intercellular Signaling Peptides and Proteins/genetics , Osteoporosis/genetics , Aged , Aged, 80 and over , Animals , Female , Heterozygote , Humans , Male , Middle Aged , Osteoporosis/pathology , Pedigree , Phenotype , Polymorphism, Single Nucleotide/genetics , Exome Sequencing , Zebrafish
14.
Gynecol Oncol ; 157(2): 529-535, 2020 05.
Article in English | MEDLINE | ID: mdl-32122688

ABSTRACT

OBJECTIVE: While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. METHODS: We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. RESULTS: Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. CONCLUSIONS: Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.


Subject(s)
Cancer Survivors/statistics & numerical data , Genital Diseases, Female/epidemiology , Ovarian Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/pathology , Registries , Utah/epidemiology , Young Adult
15.
Head Neck ; 42(4): 708-718, 2020 04.
Article in English | MEDLINE | ID: mdl-32031294

ABSTRACT

BACKGROUND: Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia. METHODS: From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model. RESULTS: Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors. CONCLUSION: We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia.


Subject(s)
Deglutition Disorders , Head and Neck Neoplasms , Deglutition Disorders/diagnosis , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/therapy , Humans , Retrospective Studies , Survivors , Utah
16.
Cancer Causes Control ; 31(3): 241-253, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32002718

ABSTRACT

Rural areas of the U.S. experience disproportionate colorectal cancer (CRC) death compared to urban areas. The authors aimed to analyze differences in CRC survival between rural and urban Utah men and investigate potential prognostic factors for survival among these men. A cohort of Utah men diagnosed with CRC between 1997 and 2013 was identified from the Utah Cancer Registry. Survival and prognostic factors were analyzed via 5-year CRC survival and Cox proportional hazards models, stratified by rural/urban residence. Among 4,660 men diagnosed with CRC, 15.3% were living in rural Utah. Compared with urban men, rural CRC patients were diagnosed at older ages and in different anatomic subsites; more were overweight, and current smokers. Differences in stage and treatment were not apparent between rural and urban CRC patients. Compared with urban counterparts, rural men experienced a lower CRC survival (Hazard Ratio 0.55, 95% CI 0.53, 0.58 vs. 0.58, 95% CI 0.56, 0.59). Race and cancer treatment influenced CRC survival among men living in both urban and rural areas. Factors of CRC survival varied greatly among urban and rural men in Utah. The influence of social and environmental conditions on health behaviors and outcomes merits further exploration.


Subject(s)
Colorectal Neoplasms/mortality , Registries , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cohort Studies , Colonic Neoplasms , Colorectal Neoplasms/ethnology , Healthcare Disparities , Humans , Male , Middle Aged , Proportional Hazards Models , Risk , Utah/epidemiology
17.
Am J Obstet Gynecol ; 223(1): 105.e1-105.e8, 2020 07.
Article in English | MEDLINE | ID: mdl-31954153

ABSTRACT

BACKGROUND: Family history of pelvic organ prolapse among first-degree relatives is an established risk factor for pelvic organ prolapse; however, consideration of the constellation of family history that extends to distant relationships allows for more accurate determination of risk and may improve pelvic organ prolapse risk prediction estimates. OBJECTIVE: The purpose of this study was to assess risk for pelvic organ prolapse treatment based on varying family histories of pelvic organ prolapse and included number and types of affected relatives, ages of relatives at pelvic organ prolapse treatment, and whether the family history is of maternal or paternal origin. STUDY DESIGN: This was a retrospective, population-based study that involved the Utah Population Database, which is a population resource that includes extensive genealogy information linked to medical records. The study population included 453,522 total women: 4628 women with a diagnosis of treated (surgical or pessary) pelvic organ prolapse and their 15,530 first-degree relatives; 33,782 second-degree relatives, and 66,469 third-degree relatives. We estimated relative risk of treated pelvic organ prolapse based on specific family history constellations. RESULTS: Relative risk estimates increased with a family history of increasing numbers of treated first-degree relatives with pelvic organ prolapse (first-degree relatives, ≥1 [relative risk, 2.36; 95% confidence interval, 2.15-2.58], first-degree relatives, ≥2 [relative risk, 3.79; 95% confidence interval, 2.65-5.24], and first-degree relatives, ≥3 [relative risk, 6.26; 95% confidence interval, 1.29-18.30]). Having a family history of ≥3 affected third-degree relatives (eg, first cousins) and no affected first- or second-degree relatives was similar in risk to having 1 affected first-degree relative. Relative risk estimates decreased with increasing age of treatment for first-degree family members. Risks in individuals with a positive maternal family history for pelvic organ prolapse were consistently higher than risks in individuals with equivalent paternal family history, but paternal inheritance still played a role. Approximately 4% of the total studied female population was found to have a >2-fold risk of being treated for pelvic organ prolapse and is considered high-risk based on their family history. CONCLUSION: We provide estimates for treated pelvic organ prolapse based on an extensive family history of pelvic organ prolapse using a large population-based sample. Risk for treated pelvic organ prolapse increased with increasing numbers of affected close and distant female relatives, earlier age of pelvic organ prolapse treatment in relatives, and maternal inheritance. These risk estimates may be useful for genetic studies and investigation of risk reduction strategies in those at highest risk for pelvic organ prolapse.


Subject(s)
Pelvic Organ Prolapse/epidemiology , Pelvic Organ Prolapse/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Medical History Taking , Middle Aged , Pelvic Organ Prolapse/genetics , Retrospective Studies , Risk Assessment , Risk Factors
18.
J Natl Cancer Inst ; 112(1): 78-86, 2020 01 01.
Article in English | MEDLINE | ID: mdl-30918958

ABSTRACT

BACKGROUND: There are an estimated 1.4 million colorectal cancer (CRC) survivors in the United States. Research on endocrine and metabolic diseases over the long term in CRC survivors is limited. Obesity is a risk factor for CRC; thus it is of interest to investigate diseases that may share this risk factor, such as diabetes, for long-term health outcomes among CRC survivors. METHODS: A total of 7114 CRC patients were identified from the Utah Population Database and matched to a general population cohort of 25 979 individuals on birth year, sex, and birth state. Disease diagnoses (assessed over three time periods of 1-5 years, 5-10 years, and >10 years) were identified using electronic medical records and statewide ambulatory and inpatient discharge data. Cox proportional hazard models were used to estimate the risk of endocrine and metabolic disease. RESULTS: Across all three time periods, risks for endocrine and metabolic diseases were statistically significantly greater for CRC survivors compared with the general population cohort. At 1-5 years postdiagnosis, CRC survivors' risk for diabetes mellitus with complications was statistically significantly elevated (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.09 to 1.70). CRC survivors also experienced a 40% increased risk of obesity at 1-5 years postcancer diagnosis (HR= 1.40, 99% CI= 1.66 to 2.18) and a 50% increased risk at 5-10 years postdiagnosis (HR = 1.50, 99% CI= 1.16 to 1.95). CONCLUSIONS: Endocrine and metabolic diseases were statistically significantly higher in CRC survivors throughout the follow-up periods of 1-5 years, 5-10 years, and more than 10 years postdiagnosis. As the number of CRC survivors increases, understanding the long-term trajectory is critical for improved survivorship care.


Subject(s)
Cancer Survivors , Colorectal Neoplasms/complications , Colorectal Neoplasms/epidemiology , Endocrine System Diseases/complications , Endocrine System Diseases/epidemiology , Metabolic Diseases/complications , Metabolic Diseases/epidemiology , Comorbidity , Endocrine System Diseases/diagnosis , Female , Humans , Kaplan-Meier Estimate , Male , Metabolic Diseases/diagnosis , Population Surveillance , Prognosis , Registries , Risk Factors , SEER Program , Utah/epidemiology
19.
Gynecol Oncol ; 156(1): 185-193, 2020 01.
Article in English | MEDLINE | ID: mdl-31839336

ABSTRACT

OBJECTIVE: The majority of endometrial cancer patients are overweight or obese at cancer diagnosis. Obesity is a shared risk factor for both endometrial cancer and diabetes, but it is unknown whether endometrial cancer patients have increased diabetes risks. The aim of our study was to investigate diabetes risk among endometrial cancer patients. METHODS: Endometrial cancer patients diagnosed between 1997 and 2012 in Utah (n = 2,314) were identified. Women from the general population (n = 8,583) were matched to the cancer patients on birth year and birth state. Diabetes diagnoses were identified from electronic medical records and statewide healthcare facility databases. Cox proportional hazards models were used to estimate hazard ratios for diabetes after cancer diagnosis. RESULTS: Endometrial cancer survivors had a significantly higher risk of type II diabetes when compared to women from the general population in the first year after cancer diagnosis (HR = 5.22, 95% CI = 4.05, 6.71), >1-5 years after cancer diagnosis (HR = 1.67, 95% CI = 1.31, 2.12), and >5 years after cancer diagnosis (HR = 1.65, 95% CI = 1.29, 2.11). Endometrial cancer patients who were obese at cancer diagnosis had a three-fold increase in type II diabetes risk (HR = 2.99, 95%CI = 2.59, 3.45). Although endometrial cancer patients diagnosed at distant stage had a higher risk of diabetes, cancer treatment did not appear to contribute to any diabetes risks. CONCLUSIONS: In conclusion, endometrial cancer survivors had a higher risk of diabetes than women in the general population. These results suggest that long term monitoring for diabetes is indicated for endometrial cancer survivors.


Subject(s)
Cancer Survivors/statistics & numerical data , Diabetes Mellitus, Type 2/epidemiology , Endometrial Neoplasms/epidemiology , Aged , Aged, 80 and over , Cohort Studies , Endometrial Neoplasms/mortality , Female , Humans , Middle Aged , Risk , SEER Program , United States/epidemiology
20.
Cancer ; 126(4): 879-885, 2020 02 15.
Article in English | MEDLINE | ID: mdl-31721181

ABSTRACT

BACKGROUND: The number of head and neck cancer (HNC) survivors has been increasing because of improving survival in the United States. The aim of this study was to evaluate the incidence of respiratory disease diagnoses in HNC survivors in comparison with cancer-free individuals. A second aim was to investigate risk factors for respiratory disease among HNC survivors. METHODS: Patients with HNC diagnosed from 1996 to 2012 were identified in the Utah Cancer Registry (n = 1901). Up to 5 cancer-free individuals from the general population (n = 7796) were matched to each HNC survivor by birth year, sex, birth state, and follow-up time. Electronic medical records and statewide health care facility data were used to identify a disease diagnosis after the cancer diagnosis. Cox proportional hazards models were used to estimate the risks of respiratory diseases. RESULTS: The median follow-up times were 4.5 years for HNC survivors and 7.8 years for the general population cohort. The risks of respiratory infection (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.40-1.90), chronic obstructive pulmonary diseases and bronchiectasis (HR, 2.65; 95% CI, 2.13-3.29), and aspiration pneumonitis (HR, 6.21; 95% CI, 3.98-9.68) were higher among HNC survivors than the general population cohort more than 5 years after the cancer diagnosis. Age at diagnosis, baseline body mass index, sex, baseline smoking status, treatment modality, primary site, and stage were associated with the risk of adverse respiratory outcomes among HNC survivors. CONCLUSIONS: The risk of adverse respiratory outcomes was much higher among HNC survivors than the general population cohort. Multidisciplinary care is needed to prevent the occurrence of adverse respiratory outcomes among HNC survivors.


Subject(s)
Cancer Survivors/statistics & numerical data , Head and Neck Neoplasms/therapy , Registries/statistics & numerical data , Respiratory Tract Diseases/diagnosis , Adult , Aged , Aged, 80 and over , Body Mass Index , Female , Head and Neck Neoplasms/epidemiology , Humans , Male , Middle Aged , Prognosis , Respiratory Tract Diseases/epidemiology , Risk Factors , Smoking , Utah/epidemiology , Young Adult
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