Environmental Contaminants Modulate Breast Cancer Development and Outcome in TP53 p.R337H Carriers and Noncarriers

SIMPLE SUMMARY: Although an inherited TP53 p.R337H mutation alone plays a critical role in breast cancer (BC) development, exposure to pesticides, industry contaminants, and air pollutants, along with poor lifestyle choices, are associated with the development of BC. The aim of our study was to assess the joint effect of the reduced tumor suppression activity of TP53 p.R337H and the environmental factors that may modulate individual susceptibility to BC. We evaluated the environmental differences and proportional distribution of TP53 p.R337H carrier and noncarrier women in three subregions of Southern Brazil to estimate the prevalence, risk, and/or mortality rate of BC. We found that a p.R337H mutation is more likely to cause BC in individuals living in a heavily polluted environment. The impact of environmental contaminants can be reduced by screening, genetic testing, medical improvements in early BC detection, and promoting healthier lifestyle practices. ABSTRACT: Two major concerns associated with cancer development in Paraná state, South Brazil, are environmental pollution and the germline TP53 p.R337H variant found in 0.27–0.30% of the population. We assessed breast cancer (BC) risk in rural (C1 and C2) and industrialized (C3) subregions, previously classified by geochemistry, agricultural productivity, and population density. C2 presents lower organochloride levels in rivers and lower agricultural outputs than C1, and lower levels of chlorine anions in rivers and lower industrial activities than C3. TP53 p.R337H status was assessed in 4658 women aged >30 years from C1, C2, and C3, subsequent to a genetic screening (Group 1, longitudinal study). BC risk in this group was 4.58 times higher among TP53 p.R337H carriers. BC prevalence and risk were significantly lower in C2 compared to that in C3. Mortality rate and risk associated with BC in women aged >30 years (n = 8181 deceased women; Group 2) were also lower in C2 than those in C3 and C1. These results suggest that environmental factors modulate BC risk and outcome in carriers and noncarriers.