Background While rural residents are more likely to be diagnosed with more advanced cancers and die of cancer, little is known about rural-urban disparities in self-reported health among survivors. Methods We identified adults with a self-reported cancer history from the National Health Interview Survey (2006–2010). Rural-urban residence was defined using US census definitions. Logistic regression with weighting to account for complex sampling was used to assess rural-urban differences in health status after accounting for differences in demographic characteristics. Results Of the 7,804 identified cancer survivors, 20.8% were rural residents. This translates to a population of 2.8 million rural cancer survivors in the US. Rural survivors were more likely than urban survivors to be non-Hispanic white (p<.001), have less education (p<.001) and lack health insurance (p<.001). Rural survivors reported worse health in all domains. After adjustment for sex, race/ethnicity, age, marital status, education, insurance, time since diagnosis, and number of cancers, rural survivors were more likely to report fair/poor health [OR=1.39, 95%CI=1.20–1.62, psychological distress [OR=1.23, 1.00–1.50], ≥2 non-cancer comorbidities [OR=1.15, 1.01–1.32], and health-related unemployment [OR=1.66, 1.35–2.03]. Conclusions We provide the first estimate of the proportion and number of US adult cancer survivors who reside in rural areas. Rural cancer survivors are at greater risk for a variety of poor health outcomes, even many years after their cancer diagnosis, and should be a target for interventions to improve their health and well-being.
A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.
Purpose Rural US adults have increased risk of poor outcomes after cancer, including increased cancer mortality. Rural-urban differences in health behaviors have been identified in the general population and may contribute to cancer health disparities, but have not yet been examined among US survivors. We examined rural-urban differences in health behaviors among cancer survivors and associations with self-reported health and health-related unemployment. Methods We identified rural (n=1,642) and urban (n=6,162) survivors from the cross-sectional National Health Interview Survey (2006–2010) and calculated the prevalence of smoking, physical activity, overweight/obesity, and alcohol consumption. Multivariable models were used to examine the associations of fair/poor health and health-related unemployment with health behaviors and rural-urban residence. Results The prevalence of fair/poor health (rural 36.7%, urban 26.6%), health-related unemployment (rural 18.5%, urban 10.6%), smoking (rural 25.3%, urban 15.8%), and physical inactivity (rural 50.7%, urban 38.7%) was significantly higher in rural survivors (all p<.05); alcohol consumption was lower (rural 46.3%, urban 58.6%), and there were no significant differences in overweight/obesity (rural 65.4%, urban 62.6%). All health behaviors were significantly associated with fair/poor health and health-related unemployment in both univariate and multivariable models. After adjustment for behaviors, rural survivors remained more likely than urban survivors to report fair/poor health (OR= 1.21, 95%CI 1.03–1.43) and health-related unemployment (OR= 1.49, 95%CI 1.18–1.88). Conclusions Rural survivors may need tailored, accessible health promotion interventions to address health compromising behaviors and improve outcomes after cancer.
Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 × 10−8 [odds ratio 4.42 (95 % confidence interval 2.56–7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 × 10−6). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-012-1229-4) contains supplementary material, which is available to authorized users.
INTRODUCTORY PARAGRAPH Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men for six ectopic fat traits in European, African, Hispanic, and Chinese ancestry populations, with and without sex stratification. In total, 7 new loci were identified in association with ectopic fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P<5×10−8; FDR<1%). Functional analysis of these genes revealed that loss of function of both ATXN1 and UBE2E2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting a physiological role for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes impact adipocyte biology and how their perturbations contribute to systemic metabolic disease.
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