Kennedy, Kathleen

6551 Background: Despite recent advances in lung cancer therapeutics leading to considerable improvement in survival, disparities continue to persist among socially disadvantaged populations. Although the reasons underlying this phenomenon are uncertain, we posit that neighborhood-level factors could play a role. Furthermore, neighborhood disadvantage may lead to epigenetic changes which promote malignant progression. This study aimed to determine the effects of neighborhood-deprivation index (NDI), a validated 13-factor-based measure, that combines income, education, employment, and housing in a neighborhood, on lung cancer mortality. Methods: A retrospective cohort study assessed the relationship of NDI with survival weighted by age, stage, and DNA methylation among biopsy-proven lung cancer from two U.S. medical centers, Johns Hopkins University and the University of Illinois Chicago, between 2008-2020. In our analysis, U.S.-standardized NDI values for each year of sample collection were computed at the U.S. census tract level and categorized into quartiles. Participants’ residential addresses were geocoded to U.S. census tracts and linked to NDI quartiles. DNA extraction from liquid biopsy samples was performed for quantification of DNA methylation. Results: The study included 184 lung cancer patients, with 89 in the low-deprivation group and 95 in the high-deprivation group. The high-deprivation group had a higher percentage of females (57% vs. 48%), a higher percentage of African Americans (AA) (50% vs. 36%), a lower pack-year smoking history (30 vs. 39 median pack-years), and a higher percentage with stage IV disease (28% vs. 20%) than the low-deprivation group. Overall, NDI was significantly higher among AA when compared with Whites (p=0.003) and associated with lung cancer stage at diagnosis with an odds ratio of 1.17 (p=0.02). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZPF42, TAC1 and HOXA9. Only HOXA7 DNA methylation correlated with NDI (p=0.003).The high-deprivation group had a significantly shorter survival duration compared to the low-deprivation group, with a 1-year survival rate of 79% vs. 90%, a 2-year survival rate of 70% vs. 84%, and a 5-year-survival rate of 51% vs. 73% (p=0.02). After adjusting for age at diagnosis, stage, and DNA methylation status, belonging to the high-deprivation group was associated with a higher mortality risk with a hazard ratio of 2.02 (p=0.04). Conclusions: Neighborhood-level socioeconomic status and DNA methylation may be associated with late stage lung cancer at diagnosis; whereas NDI shows a potential association with shorter survival and increased mortality risk. Higher neighborhood deprivation among AA suggests that changes in health care policy that account for neighborhood-level indices of socioeconomic deprivation may enable more equitable improvement of lung cancer mortality.

Abstract Recent publications have reported that common variants on 8q24 are associated with both prostate and colorectal cancers (CRC). In addition, one of these studies (the ARCTIC study) initially observed an association with a single nucleotide polymorphism (SNP) on 9p24 that was not confirmed in some of their validation data sets. In the research described here, we conducted a case-unaffected sibling analysis using population- and clinic-based discordant sibships (N = 1,567 sibships) from the Colon Cancer Family Registry (Colon CFR) to investigate the associations between common variants at 9p24 and 8q24 and risk of CRC. We also evaluated whether these associations differed by age, family history, and tumor characteristics, including microsatellite instability and tumor site. Associations were estimated using conditional logistic regression, treating sibship as the matching factor. Analyses were adjusted for age and sex, and stratified by ascertainment source (population versus clinic). We observed an association between a SNP on 9p24 (rs719725) and risk of CRC in the population-based series (AA versus CC: odds ratios, 1.46; 95% confidence interval, 1.06–2.02; AC versus CC: odds ratios, 1.50; 95% confidence interval, 1.14–1.98; P = 0.011 on 2 df). In the population-based series, we also detected statistically significant associations between two SNPs on 8q24, rs10505477 and rs6983267, and risk of CRC (P = 0.005 and P = 0.002, respectively). There was no evidence of statistically significant heterogeneity by age at diagnosis, family history of CRC, microsatellite instability, or tumor site at either locus and no evidence of interaction between SNPs on 8q24 and 9p24. These data suggest that common variants may play important roles in the risk of CRC. [Cancer Res 2007;67(23):11128–32]