BackgroundHigh levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk.MethodsWe analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance.ResultsTwo variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06–1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02–1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by ‘never use’ of HRT and/or non-obese BMI. No variants were associated with CRC among men.ConclusionsLeptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.

Background: Income inequality has been associated with greater mortality and lower life expectancy in many ecologic studies, particularly at the national level. At the neighborhood level, the influence of income inequality on individual health is less clear. Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Recent studies suggest that neighborhood social and built environments are associated with outcomes across the CRC continuum, including screening, risk, and survival. Few studies of neighborhood factors have examined income inequality in relation to CRC survival. Methods: We examined the association of census tract-level income inequality with survival among women who participated in the Women's Health Initiative (WHI) and were diagnosed with incident invasive CRC between 1994-2014 (N=2,595). Based on geocoded residence at diagnosis and year of diagnosis, we linked each participant to census tract-level data from the US Census and American Community Survey (ACS). Within each tract, income inequality was assessed using the ratio of the 95th and 20th percentiles for household income. Quartiles for 95/20 ratio were constructed from the distribution of 95/20 ratios across all U.S. census tracts with more than 50 households. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall and disease-specific survival. Models were adjusted for age at diagnosis, year of diagnosis, individual household income, and tract-level percent of households in poverty; subsequent models also adjusted for tumor stage at diagnosis. To explore whether the relationship between income inequality and survival differed by individual or tract-level sociodemographic characteristics, we conducted analyses stratified by race/ethnicity, individual household income, and tract-level poverty. Results: Compared to women residing in low-income-inequality census tracts, women living in tracts with the highest income inequality had modestly poorer overall survival (HR=1.24, 95% CI: 1.01-1.51, comparing highest and lowest quartiles). However, this association was not significant after adjustment for stage at diagnosis. No associations were detected for disease-specific survival. The associations between income inequality and overall or disease-specific survival were not modified by tract-level poverty, individual household income, or race/ethnicity. Conclusion: There was no association between census tract-level income inequality and CRC survival in our study. Our results suggest that the association may be confounded or even mediated by disparities in stage at diagnosis. Citation Format: Kelsey A. Chun, Jamaica R. Robinson, Candace H. Kroenke, Dorothy S. Lane, Giselle Corbie-Smith, Theresa Hastert, Shawnita Sealy-Jefferson, Manali I. Patel, Kathy Pan, Shirley A.A. Beresford, Polly A. Newcomb. Census tract-level income inequality and colorectal cancer survival [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C068.