Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

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.

Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah.

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.

Characteristics of missed or interval colorectal cancer and patient survival: a population-based study.

BACKGROUND & AIMS: Colorectal cancers (CRCs) diagnosed within a few years after an index colonoscopy can arise from missed lesions or the development of a new tumor. We investigated the proportion, characteristics, and factors that predict interval CRCs that develop within 6-60 months of colonoscopy. METHODS: We performed a population-based cohort study of Utah residents who underwent colonoscopy examinations from 1995 through 2009 at Intermountain Healthcare or the University of Utah Health System, which provide care to more than 85% of state residents. Colonoscopy results were linked with cancer histories from the Utah Population Database to identify patients who underwent colonoscopy 6-60 months before a diagnosis of CRC (interval cancer). Logistic regression was performed to identify risk factors associated with interval cancers. RESULTS: Of 126,851 patients who underwent colonoscopies, 2659 were diagnosed with CRC; 6% of these CRCs (159 of 2659) developed within 6 to 60 months of a colonoscopy. Sex and age were not associated with interval CRCs. A higher percentage of patients with interval CRC were found to have adenomas at their index colonoscopy (57.2%), compared with patients found to have CRC detected at colonoscopy (36%) or patients who did not develop cancer (26%) (P < .001). Interval CRCs tended to be earlier-stage tumors than those detected at index colonoscopy, and to be proximally located (odds ratio, 2.24; P < .001). Patients with interval CRC were more likely to have a family history of CRC (odds ratio, 2.27; P = .008) and had a lower risk of death than patients found to have CRC at their index colonoscopy (hazard ratio, 0.63; P < .001). CONCLUSIONS: In a population-based study in Utah, 6% of all patients with CRC had interval cancers (cancer that developed within 6 to 60 months of a colonoscopy). Interval CRCs were associated with the proximal colon, earlier-stage cancer, lower risk of death, higher rate of adenoma, and family history of CRC. These findings indicate that interval colorectal tumors may arise as the result of distinct biologic features and/or suboptimal management of polyps at colonoscopy.

Risk of colorectal cancer and adenomas in the families of patients with adenomas: a population-based study in Utah.

BACKGROUND: Guidelines recommend that individuals with a first-degree relative (FDR) diagnosed with colorectal cancer (CRC) or advanced adenoma before age 60 years should undergo colonoscopy starting at age 40 years. The authors quantified the risk of adenomas and CRC in FDRs, second-degree relatives (SDRs), and third-degree relatives (TDRs) of patients diagnosed with adenomas and advanced adenomas. METHODS: A population-based, retrospective, case-control study was performed of residents of the state of Utah aged 50 years to 80 years who underwent colonoscopy between 1995 and 2009 at Intermountain Healthcare or the University of Utah. Controls were selected from the population of colonoscopy patients who were free of adenomas or CRC and matched to each case based on sex and birth year. Colonoscopy results were linked with cancer and pedigree information from the Utah Population Database to investigate the familial aggregation of adenomas and CRC using Cox regression analysis. The unit of analysis was the relatives of cases and controls. RESULTS: Of 126,936 patients who underwent colonoscopy, 43,189 had adenomas and 5563 had advanced adenomas and defined the case population. An elevated risk of CRC was found in FDRs (relative risk [RR], 1.35; 95% confidence interval [95% CI], 1.25-1.46), SDRs (RR, 1.15; 95% CI, 1.07-1.23) of adenoma cases, and in FDRs of advanced adenoma cases (RR, 1.68; 95% CI, 1.29-2.18) compared with controls. Approximately 10% of CRCs diagnosed in relatives would have been missed if the current screening guidelines were strictly adhered to. CONCLUSIONS: Relatives of colonoscopy patients with adenomas and advanced adenomas appear to have a significantly elevated risk of developing colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and their families.

Familial clustering of endometrial cancer in a well-defined population.

OBJECTIVE: Using a genealogical database, we examined risk of endometrial cancer among family members of individuals with endometrial cancer. METHODS: We identified endometrial cancer cases in the Utah Population Database (UPDB), a computerized archive of genealogy data linked to the Utah Cancer Registry. We tested for excess relatedness and estimated relative risks (RR) among first-, second-, and third-degree relatives of endometrial cancer cases and stratified analyses by tumor histology and body mass index (BMI). RESULTS: We identified 3911 cases; 3546 were Type I cancers and 365 Type II cancers. The RR for all endometrial cancer cases and for cases with type I histology was significantly increased for first-, second-, and third-degree relatives. An almost three-fold risk was observed among first-degree relatives of individuals with Type I cancers and a 2.24-fold risk among second-degree relatives of Type I morbidly obese cases. The magnitude of endometrial cancer risk among relatives appeared to increase with case BMI. CONCLUSIONS: The elevated risks for endometrial cancer among first-, second-, and third-degree relatives support a genetic contribution to predisposition to endometrial cancer. The increased risk appears to be limited to Type I endometrial cancer. We observed increased risks for endometrial cancer among relatives of obese and morbidly obese Type I cases, which may be indicative of a synergistic relationship between underlying genetic propensity and shared environment. This study quantifies risk of developing cancer among relatives of patients with disease and provides the basis for further analysis of high risk pedigrees and gene identification for genetic etiologies of endometrial cancer.

Mental Health Disorders are More Common in Colorectal Cancer Survivors and Associated With Decreased Overall Survival.

OBJECTIVES: To determine the risk and risk factors for mental illness among colorectal cancer (CRC) survivors across short-term and long-term follow-up periods. METHODS: We used the Utah Cancer Registry to identify CRC survivors diagnosed between 1997 and 2013. Mental health diagnoses were available in electronic medical records and statewide facilities data that were linked by the Utah Population Database. CRC survivors were matched to individuals from a general population cohort. The risk of developing a mental illness was compared between cohorts. The association between mental illness and mortality was also analyzed. RESULTS: In total, 8961 CRC survivors and 35,897 individuals in a general population cohort were identified. CRC survivors were at increased risk for any mental health diagnosis at 0 to 2 years (hazard ratio [HR], 3.70; 95% confidence interval [CI], 3.47-3.95), >2 to 5 years (HR, 1.23; 95% CI, 1.09-1.38), and >5 years (HR, 1.20; 95% CI, 1.07-1.36) after cancer diagnosis. CRC survivors were also at increased risk of depressive disorders specifically during the same time periods. At >5 years, CRC survivors still had an increased risk of developing many mental health diagnoses. Factors associated with increased risk of any mental health disorder among CRC survivors included colostomy and Charlson Comorbidity Index of 1+. There was an increased risk of death for CRC survivors diagnosed with any mental health disorder (HR, 2.18; 95% CI, 2.02-2.35) and depression (HR, 2.10; 95% CI, 1.92-2.28). CONCLUSIONS: CRC survivors are at increased risk for mental health disorders in the short-term and long-term. Survivors who develop mental health disorders also experience decreased survival.

A genealogical assessment of heritable predisposition to aneurysms.

OBJECT: This study was conducted to investigate the familial and genetic contribution to intracranial, abdominal aortic, and all other types of aneurysms, and to define familial relationships among patients who present with the different aneurysm types. METHODS: The authors used a unique Utah resource to perform population-based analysis of the familial nature of aneurysms. The Utah Population Data Base is a genealogy of the Utah population dating back eight generations, which is combined with death certificate data for the state of Utah dating back to 1904. Taking into account the genetic relationships among all aneurysm cases derived from this resource, the authors used a previously published method to estimate the familiality of different aneurysm types. Using internal, birth-cohort-specific rates of disease calculated from the database, they estimated relative risks by comparing observed to expected rates of aneurysm incidence in defined sets of relatives of probands. CONCLUSIONS: Each of the three aneurysm types investigated showed significant evidence for a genetic component. Relatives of patients with intracranial aneurysms do not appear to be at increased risk for abdominal or other lesions, but relatives of patients with abdominal aortic aneurysms appear to be at increased risk for other types of these lesions.

Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders.

Major depressive disorder (MDD) is a common, clinically heterogeneous disorder often found comorbid with other disorders. We studied recurrent, early-onset MDD (MDD-RE) and anxiety disorders in combination to define powerful phenotypes for genetic study. We used 87 large, extended Utah pedigrees to investigate linkage to 3 phenotypes: "MDD-RE;" "MDD-RE or anxiety;" and "MDD-RE and anxiety;" where in the latter definition the disorders must appear comorbid within an individual. Pedigrees ranged in size from 2 to 6 generations and contained 3 to 42 individuals affected with MDD or anxiety (718 total). In primary analyses, we identified three regions with at least suggestive genome-wide evidence for linkage on chromosomes 3centr, 7p, and 18q. Both 7p and 18q are replication findings for related phenotypes. The best linkage evidence was for a novel locus at 3p12.3-q12.3 (LOD = 3.88, "MDD-RE or anxiety") and 18q21.33-q22.2 (LOD = 3.75, "MDD-RE and anxiety"), a well-established susceptibility locus for bipolar disorder. In our secondary sex-specific analyses, we identified two further regions of interest on chromosomes 4q and 15q. Using linked pedigrees, we localized 3centr and 18q to 9.8 and 12.2 cM, respectively, with potential for further localization with the addition of markers in specific pedigrees. Our success in replication and novel locus identification illustrates the utility of large extended pedigrees for common disorders, such as MDD. Further, it supports the hypothesis that MDD and anxiety disorders have over-lapping genetic etiologies and suggests that comorbid diagnoses may be useful in defining more genetically homogeneous forms of MDD for linkage mapping.