Risk of Incident Colorectal Cancer and Death After Colonoscopy: A Population-based Study in Utah.

BACKGROUND & AIMS: Colonoscopy is widely recommended for colorectal (CRC) screening in the United States, but evidence of effectiveness is limited. We examined whether exposure to colonoscopy decreases the odds of incident CRC and death from CRC in Utah. METHODS: We performed a case-control study of Utah residents, 54 to 90 years old, who received a CRC diagnosis from 2000 through 2010 (cases). Age- and sex-matched controls with no history of CRC (controls) were selected for each case. We determined receipt of colonoscopy 6 months to 10 years before the reference date for each case and control through administrative claims data. Colonoscopy exposure was compared by using conditional logistic regression. RESULTS: We identified 5128 cases and 20,512 controls; 741 cases (14%) and 5715 controls (28%) received a colonoscopy. Exposure to colonoscopy reduced the odds for a diagnosis of CRC; the odds ratios (ORs) were 0.41 for any CRC (95% confidence interval [CI], 0.38-0.44), 0.58 for proximal colon cancer (95% CI, 0.51-0.65), and 0.29 for distal colon or rectal cancer (95% CI, 0.25-0.33). This finding was consistent among sexes, age groups, and cancer stages. Similarly, in a subgroup analysis, colonoscopy was associated with decreased odds of death from CRC (OR, 0.33; 95% CI, 0.28-0.39) in both the proximal colon (OR, 0.43; 95% CI, 0.34-0.55) and distal colon or rectum (OR, 0.23; 95% CI, 0.18-0.30). CONCLUSIONS: In the population of Utah, colonoscopy is associated with a large reduction in risk of new-onset CRC and death from CRC. This reduction in risk for CRC was greatest for the distal colon and rectum, with a more modest reduction for proximal colon cancer.

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.

Epidemiology and familial risk of synchronous and metachronous colorectal cancer: a population-based study in Utah.

BACKGROUND & AIMS: Patients diagnosed with colorectal cancer (CRC) are at risk for synchronous and metachronous lesions at the time of diagnosis or during follow-up evaluation. We performed a population-based study to evaluate the rate, predictors, and familial risk for synchronous and metachronous CRC in Utah. METHODS: All newly diagnosed cases of CRC between 1980 and 2010 were obtained from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. RESULTS: Of the 18,782 patients diagnosed with CRC, 134 were diagnosed with synchronous CRC (0.71%) and 300 were diagnosed with metachronous CRC (1.60%). The risk for synchronous CRC was significantly higher in men (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.02-2.06) and in patients aged 65 years or older (OR, 1.50; 95% CI, 1.02-2.21). Synchronous CRCs were located more often in the proximal colon (OR, 1.70; 95% CI, 1.20-2.41). First-degree relatives of cases with synchronous (OR, 1.86; 95% CI, 1.37-2.53), metachronous (OR, 2.34; 95% CI, 1.62-3.36), or solitary CRC (OR, 1.75; 95% CI, 1.63-1.88) were at increased risk for developing CRC, compared with relatives of CRC-free individuals. Four percent of first-degree relatives of patients with synchronous or metachronous cancer developed CRC at younger ages than the age recommended for initiating CRC screening (based on familial risk), and therefore would not have been screened. CONCLUSIONS: Of patients diagnosed with CRC, 2.3% are found to have synchronous lesions or develop metachronous CRC during follow-up evaluation. Relatives of these patients have a greater risk of CRC than those without a family history of CRC. These results highlight the importance of obtaining a thorough family history and adhering strictly to surveillance guidelines during management of high-risk patients.

Survival of offspring who experience early parental death: early life conditions and later-life mortality.

We examine the influences of a set of early life conditions (ELCs) on all-cause and cause-specific mortality among elderly individuals, with special attention to one of the most dramatic early events in a child's, adolescent's, or even young adult's life, the death of a parent. The foremost question is, once controlling for prevailing (and potentially confounding) conditions early in life (family history of longevity, paternal characteristics (SES, age at time of birth, sibship size, and religious affiliation)), is a parental death associated with enduring mortality risks after age 65? The years following parental death may initiate new circumstances through which the adverse effects of paternal death operate. Here we consider the offspring's marital status (whether married; whether and when widowed), adult socioeconomic status, fertility, and later life health status. Adult health status is based on the Charlson Co-Morbidity Index, a construct that summarizes nearly all serious illnesses afflicting older individuals that relies on Medicare data. The data are based on linkages between the Utah Population Database and Medicare claims that hold medical diagnoses data. We show that offspring whose parents died when they were children, but especially when they were adolescents/young adults, have modest but significant mortality risks after age 65. What are striking are the weak mediating influences of later-life comorbidities, marital status, fertility and adult socioeconomic status since controls for these do little to alter the overall association. No beneficial effects of the surviving parent's remarriage were detected. Overall, we show the persistence of the effects of early life loss on later-life mortality and indicate the difficulties in addressing challenges at young ages.

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 aggregation of childhood and adult cancer in the Utah genealogy.

A small proportion of childhood cancer is attributable to known hereditary syndromes, but whether there is any familial component to the remainder remains uncertain. We explored familial aggregation of cancer in a population-based case-control study using genealogical record linkage and designed to overcome limitations of previous studies. Subjects were selected from the Utah Population Database. We compared risk of cancer in adult first-degree relatives of children who were diagnosed with cancer with the risk in relatives of children who had not had a cancer diagnosed. We identified 1,894 childhood cancer cases and 3,788 controls; 7,467 relatives of cases and 14,498 relatives of controls were included in the analysis. Relatives of children with cancer had a higher risk of cancer in adulthood than relatives of children without cancer [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.11-1.56]; this was restricted to mothers and siblings and was not evident in fathers. Familial aggregation appeared stronger among relatives of cases diagnosed before 5 years of age (OR 1.48, 95% CI 1.13-1.95) than among relatives of cases who were older when diagnosed (OR 1.22, 95% CI 0.98-1.51). These findings provide evidence of a generalized excess of cancer in the mothers and siblings of children with cancer. The tendency for risk to be higher in the relatives of children who were younger at cancer diagnosis should be investigated in other large data sets. The excesses of thyroid cancer in parents of children with cancer and of any cancer in relatives of children with leukemia merit further investigation.

The male-female health-survival paradox and sex differences in cohort life expectancy in Utah, Denmark, and Sweden 1850-1910.

PURPOSE: In Utah, the prevalence of unhealthy male risk behaviors are lower than in most other male populations, whereas women experience higher mortality risk because of higher fertility rates. Therefore, we hypothesize that the Utah sex differential in mortality would be small and less than in Sweden and Denmark. METHODS: Life tables from Utah, Denmark, and Sweden were used to calculate cohort life expectancies for men and women born in 1850-1910. RESULTS: The sex difference in cohort life expectancy was similar or larger in Utah when compared with Denmark and Sweden. The change over time in the sex differences in cohort life expectancy was approximately 2 years smaller for active Mormons in Utah than for other groups suggesting lifestyle as an important component for the overall change seen in cohort life expectancy. Sex differences in cohort life expectancy at the age of 50 years were similar for individuals actively affiliated with the Church of Jesus Christ of Latter-day Saints and for Denmark and Sweden. CONCLUSIONS: The hypothesis that a smaller sex difference in cohort life expectancies in Utah would be detected in relation to Denmark and Sweden was not supported. In Utah, the male-female differences in life expectancy remain substantial pointing toward biological mechanisms or other unmeasured risk factors.

Identifying clinical/translational research cohorts: ascertainment via querying an integrated multi-source database.

BACKGROUND: Ascertainment of potential subjects has been a longstanding problem in clinical research. Various methods have been proposed, including using data in electronic health records. However, these methods typically suffer from scaling effects-some methods work well for large cohorts; others work for small cohorts only. OBJECTIVE: We propose a method that provides a simple identification of pre-research cohorts and relies on data available in most states in the USA: merged public health data sources. MATERIALS AND METHODS: The Utah Population Database Limited query tool allows users to build complex queries that may span several types of health records, such as cancer registries, inpatient hospital discharges, and death certificates; in addition, these can be combined with family history information. The architectural approach incorporates several coding systems for medical information. It provides a front-end graphical user interface and enables researchers to build and run queries and view aggregate results. Multiple strategies have been incorporated to maintain confidentiality. RESULTS: This tool was rapidly adopted; since its release, 241 users representing a wide range of disciplines from 17 institutions have signed the user agreement and used the query tool. Three examples are discussed: pregnancy complications co-occurring with cardiovascular disease; spondyloarthritis; and breast cancer. DISCUSSION AND CONCLUSIONS: This query tool was designed to provide results as pre-research so that institutional review board approval would not be required. This architecture uses well-described technologies that should be within the reach of most institutions.

Effects of BRCA1 and BRCA2 mutations on female fertility.

Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly for BRCA1/2 mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played by BRCA1/2 mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.

Evaluation of record linkage between a large healthcare provider and the Utah Population Database.

OBJECTIVE: Electronically linked datasets have become an important part of clinical research. Information from multiple sources can be used to identify comorbid conditions and patient outcomes, measure use of healthcare services, and enrich demographic and clinical variables of interest. Innovative approaches for creating research infrastructure beyond a traditional data system are necessary. MATERIALS AND METHODS: Records from a large healthcare system's enterprise data warehouse (EDW) were linked to a statewide population database, and a master subject index was created. The authors evaluate the linkage, along with the impact of missing information in EDW records and the coverage of the population database. The makeup of the EDW and population database provides a subset of cancer records that exist in both resources, which allows a cancer-specific evaluation of the linkage. RESULTS: About 3.4 million records (60.8%) in the EDW were linked to the population database with a minimum accuracy of 96.3%. It was estimated that approximately 24.8% of target records were absent from the population database, which enabled the effect of the amount and type of information missing from a record on the linkage to be estimated. However, 99% of the records from the oncology data mart linked; they had fewer missing fields and this correlated positively with the number of patient visits. DISCUSSION AND CONCLUSION: A general-purpose research infrastructure was created which allows disease-specific cohorts to be identified. The usefulness of creating an index between institutions is that it allows each institution to maintain control and confidentiality of their own information.

The impact of a growing minority population on identification of duplicate records in an enterprise data warehouse.

Patient medical records are often fragmented across disparate healthcare databases, potentially resulting in duplicate records that may be detrimental to health care services. These duplicate records can be found through a process called record linkage. This paper describes a set of duplicate records in a medical data warehouse found by linking to an external resource containing family history and vital records. Our objective was to investigate the impact database characteristics and linkage methods have on identifying duplicate records using an external resource. Frequency counts were made for demographic field values and compared between the set of duplicate records, the data warehouse, and the external resource. Considerations for understanding the relationship that records labeled as duplicates have with dataset characteristics and linkage methods were identified. Several noticeable patterns were identified where frequency counts between sets deviated from what was expected including how the growth of a minority population affected which records were identified as duplicates. Record linkage is a complex process where results can be affected by subtleties in data characteristics, changes in data trends, and reliance on external data sources. These changes should be taken into account to ensure any anomalies in results describe real effects and are not artifacts caused by datasets or linkage methods. This paper describes how frequency count analysis can be an effective way to detect and resolve anomalies in linkage results and how external resources that provide additional contextual information can prove useful in discovering duplicate records.

Quantification of the familial contribution to juvenile idiopathic arthritis.

OBJECTIVE: We previously demonstrated that there is familial aggregation of juvenile idiopathic arthritis (JIA). Using a large JIA cohort, we sought to identify additional clusters of JIA cases and to calculate robust estimates of the relative risk (RR) of JIA in the siblings and cousins of JIA probands. We also estimated the population attributable risk (PAR) of familial factors in JIA. METHODS: A probabilistic record-linking analysis was performed by matching the records of 862 patients with JIA with the records of approximately 7 million individuals in the Utah Population Database (UPDB), a computerized genealogic database. For each patient, 5 control subjects matched for birth year and sex were selected from the UPDB. Specialized software was used to test for familial aggregation of disease, to estimate the magnitude of familial risks, and to identify families at high risk of disease. RESULTS: We identified 22 founders who had significantly more descendants with JIA than expected (5-13 descendants; P values ranged from <0.0001 to <0.008). The PAR of familial factors for JIA was approximately 13%. The RR of JIA in the siblings of patients was significantly increased (11.6, 95% confidence interval [95% CI] 4.9-27.5, P < 2.59 x 10(-8)). The RR of JIA in first cousins was also increased (5.82, 95% CI 2.5-13.8, P < 6.07 x 10(-5)). CONCLUSION: We have identified the largest sets of JIA pedigrees described to date. Approximately 13% of cases of JIA can be attributed to familial factors. Siblings and first cousins of probands with JIA have an increased risk of JIA. The observed decline in the magnitude of risk between siblings and cousins suggests that JIA is influenced by shared genetic factors.

Population-based assessment of familial inheritance and neurologic comorbidities among patients with an isolated atrial septal defect.

BACKGROUND: Interatrial shunts, caused by either atrial septal defect (ASD) or patent foramen ovale, have been reported to have a familial association. We sought to examine the familial risk of isolated interatrial shunt and explore associated comorbidities of stroke, transient ischemic attack (TIA), and migraine using a population database. METHODS: The Utah Population Database is linked to inpatient and outpatient records from the University of Utah Health Science Center. Patients with an interatrial shunt were identified, and those with any other form of congenital heart disease or an inheritable syndrome associated with ASD were excluded. Of the 9452 individuals diagnosed with isolated interatrial shunt, 6179 (65%) had sufficient familial and follow-up data for analysis. Five age/gender matched controls were randomly selected per case. Cases and their relatives were compared with controls to assess the relative risk for each comorbid condition. RESULTS: Relatives of interatrial shunt cases had an increased risk for interatrial shunt: siblings relative risk (RR) 6.98 (95% confidence interval [CI] 5.75-8.48; P < 1.0 x 10(-16)), first-degree RR 5.64 (95% CI 4.76-6.68; P < 1.0 x 10(-16)), and second-degree RR 1.75 (95% CI 1.32-2.32; P= 0.0001). Patients with interatrial shunt were more likely to have a comorbid condition compared with controls (RR 21.3, 95% CI 17.1-26.5; P < 1.0 x 10(-16)). First-degree relatives of cases had an increased risk of TIA (RR 1.70, 95% CI 1.18-2.45; P= 0.0045), but no increase risk of stroke or migraine compared with controls. CONCLUSIONS: There is a strong familial inheritance pattern for isolated interatrial shunt, with significantly higher risk of interatrial shunt among affected patients' siblings, first-, and second-degree relatives. Relatives of affected individuals also had a higher risk of TIA, a trend toward an increased risk for stroke, but no increased risk of migraine headache.

Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis.

OBJECTIVE: To compare birth outcomes among female survivors of childhood and adolescent cancer who subsequently bear children, relative to those of women without a history of cancer. DESIGN: Retrospective cohort study. SETTING: Four US regions. PARTICIPANTS: Cancer registries identified girls younger than 20 years who were diagnosed as having cancer from 1973 through 2000. Linked birth records identified the first live births after diagnosis (n = 1898). Comparison subjects were selected from birth records (n = 14 278). Survivors of genital tract carcinomas underwent separate analysis. MAIN EXPOSURE: Cancer diagnosis at younger than 20 years. MAIN OUTCOME MEASURES: Infant low birth weight, preterm delivery, sex ratio, malformations, mortality, and delivery method, and maternal diabetes, anemia, and preeclampsia. RESULTS: Infants born to childhood cancer survivors were more likely to be preterm (relative risk [RR], 1.54; 95% confidence interval [CI], 1.30-1.83) and to weigh less than 2500 g (1.31; 1.10-1.57). For the offspring of genital tract carcinoma survivors, RRs were 1.33 (95% CI, 1.13-1.56) and 1.29 (1.10-1.53), respectively. There were no increased risks of malformations, infant death, or altered sex ratio, suggesting no increased germ cell mutagenicity. In exploratory analysis, bone cancer survivors had an increased risk of diabetes (RR, 4.92; 95% CI, 1.60-15.13), and anemia was more common among brain tumor survivors (3.05; 1.16-7.98) and childhood cancer survivors whose initial treatment was chemotherapy only (2.45; 1.16-5.17). CONCLUSIONS: Infants born to female survivors of childhood and adolescent cancer were not at increased risk of malformations or death. Increased occurrence of preterm delivery and low birth weight suggest that close monitoring is warranted. Increased diabetes and anemia among subgroups have not been reported, suggesting areas for study.

Reproductive outcomes in male childhood cancer survivors: a linked cancer-birth registry analysis.

OBJECTIVE: To compare the risk of reproductive and infant outcomes between male childhood cancer survivors and a population-based comparison group. DESIGN: Retrospective cohort study. SETTING: Four US regions. PARTICIPANTS: Cancer registries identified males younger than 20 years diagnosed with cancer from 1973 to 2000. Linked birth certificates identified first subsequent live offspring (N = 470). Comparison subjects were identified from remaining birth certificates, frequency-matched on year and age at fatherhood, and race/ethnicity (N = 4150). MAIN EXPOSURE: Cancer diagnosis before age 20 years. OUTCOME MEASURES: Pregnancy and infant outcomes identified from birth certificates. RESULTS: Compared with infants born to unaffected males, offspring of cancer survivors had a borderline risk of having a birth weight less than 2500 g (relative risk, 1.43 [95% confidence interval, 0.99-2.05]) that was associated most strongly with younger age at cancer diagnosis and exposure to any chemotherapy (1.96 [1.22-3.17]) or radiotherapy (1.95 [1.14-3.35]). However, they were not at risk of being born prematurely, being small for gestational age, having malformations, or having an altered male to female ratio. Overall, female partners of male survivors were not more likely to have maternal complications recorded on birth records vs the comparison group. However, preeclampsia was associated with some cancers, especially central nervous system tumors (relative risk, 3.36 [95% confidence interval, 1.63-6.90]). CONCLUSIONS: Most pregnancies resulting in live births among partners of male childhood cancer survivors were not at significantly greater risk of complications vs comparison subjects. However, there remains the possibility that prior cancer therapy may affect male germ cells with some effects on progeny and on female partners.

Familial aggregation of survival and late female reproduction.

Women giving birth at advanced reproductive ages in natural fertility conditions have been shown to have superior postmenopausal longevity. It is unknown whether improved survival is more likely among relatives of late-fertile women. This study compares survival past age 50 of men with and without a late-fertile sister in two populations: Utahns born in 1800-1869 identified from the Utah Population Database and Québec residents born in 1670-1750 identified from the Programme de recherche en démographie historique. Male survival was greater for those with, rather than without, a sister reproducing after age 45, particularly among men with at least three sisters (Utah rate ratio [RR] = .801, 95% CI = 0.687-0.940; Quebec RR = .786, 95% CI = 0.664-0.931). Survival of wives was unaffected by whether their husbands had a late-fertile sister, suggesting a weak influence of unmeasured socioenvironmental factors. These results support the hypothesis that late female fertility and slow somatic aging may be promoted by the same genetic variants.

Effects of childhood and middle-adulthood family conditions on later-life mortality: evidence from the Utah Population Database, 1850-2002.

We examine how key early family circumstances affect mortality risks decades later. Early-life conditions are measured by parental mortality, parental fertility (e.g., offspring sibship size, parental age at offspring birth), religious upbringing, and parental socioeconomic status. Prior to these early-life conditions are familial and genetic factors that affect life span. Accordingly, we consider the role of parental and familial longevity on adult mortality risks. We analyze the large Utah Population Database which contains a vast amount of genealogical and other vital/health data that contain full life histories of individuals and hundreds of their relatives. To control for unobserved heterogeneity, we analyze sib-pair data for 12,000 sib-pairs using frailty models. We found modest effects of key childhood conditions (birth order, sibship size, parental religiosity, parental SES, and parental death in childhood). Our measures of familial aggregation of longevity were large and suggest an alternative view of early-life conditions.