Impact of arsenic exposure on clinicopathological characteristics of bladder cancer: A comparative study between patients from an arsenic-exposed region and nonexposed reference sites.

BACKGROUND: Beyond exposure to arsenic in drinking-water, there is few information about demographic and clinicopathological features of patients with bladder cancer living in arsenic-exposed regions. The aim of the study was to assess the impact of arsenic exposure on clinicopathological characteristics in patients with bladder cancer from a contaminated region compared to those of 2 reference areas. METHODS: Data of 285 patients with bladder cancer (83 with arsenic exposure from Antofagasta and 202 controls from 2 different sites in Santiago) were obtained through personal interviews and from review of medical records. Demographic, clinicopathological parameters, and information on relevant environmental risk factors were compared with parametric and nonparametric tests as needed. Multivariable analysis was performed to identify independent predictors for high grade and muscle-invasive disease (T2-4). RESULTS: We found no significant differences between groups regarding age at presentation (66.4 vs. 66.5 and 67.2 years; P = 0.69, for exposed vs. the 2 nonexposed groups, respectively) and female gender (28.9% vs. 29.8% and 26.2%; P = 0.84). Proportion of current smokers was significantly lower in the exposed population (10.7% vs. 38.6% and 26.9%; P < 0.001). There was a significantly higher proportion of locally advanced (10.8 vs. 1.8 and 0.7% T3/4; P = 0.002) and high-grade tumors (79.5% vs. 63.2% and 64.1%; P = 0.001) within arsenic-exposed patients. Arsenic exposure was the only significant predictor for the presence of high-grade tumors (adjusted OR: 5.10; 95%CI: 2.03-12.77) on multivariable analysis. CONCLUSIONS: Our study revealed relevant clinical differences in bladder cancer patients with a history of arsenic exposure as compared to nonexposed cases. The more aggressive phenotype associated to arsenic-related bladder cancer should be considered when designing efficient screening strategies for this high-risk population.

Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert.

Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests-PBSn1 and an ancestry-enrichment test-in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P = 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P = 1.3 × 10-9) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.