Neighborhood disadvantage is associated with KRAS-mutated non-small cell lung cancer risk

J Cancer Res Clin Oncol. 2023 Jul;149(8):5231-5240. doi: 10.1007/s00432-022-04455-7. Epub 2022 Nov 16.

Abstract

Purpose: It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements.

Methods: We analyzed data from 429 NSCLC patients treated at a Comprehensive Cancer Center from 2015 to 2018. Data were abstracted from medical records and each patient's home address was used to assign publicly available indices of neighborhood disadvantage. Prevalence Ratios (PRs) for the presence of somatic KRAS mutations were estimated using modified Poisson regression models adjusted for age, sex, smoking status, race/ethnicity, educational attainment, cancer stage, and histology.

Results: In the NSCLC cohort, 29% had KRAS mutation-positive tumors. We found that five deprivation indices of socioeconomic disadvantage were associated with KRAS mutation. A one decile increase in several of these socioeconomic disadvantage indices was associated with a 1.06 to 1.14 increased risk of KRAS mutation. Measures of built structural environment were not associated with KRAS mutation status.

Conclusion: Socioeconomic disadvantage at the neighborhood level is associated with higher risk of KRAS mutation while disadvantage related to built environmental structural measures was inversely associated. Our results indicate not only that neighborhood disadvantage may contribute to aggressive NSCLC biology, but the pathways linking biology to disadvantage are likely operating through socioeconomic-related stress.

Keywords: Health disparities; KRAS mutations; Molecular epidemiology; Neighborhood socioeconomic status; Non-small cell lung cancer.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / epidemiology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / genetics
  • Mutation
  • Neighborhood Characteristics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Residence Characteristics

Substances

  • Proto-Oncogene Proteins p21(ras)
  • KRAS protein, human