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

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.

Spatial trends in congenital malformations and stream water chemistry in Southern Brazil.

The incidence of variable congenital malformation (CM) among 399 municipalities in the state of Paraná, southern Brazil, suggests the etiological role of environmental factors. This study examined a) environmental concentrations of chlorine anions (Cl-) associated with organochlorines (OCs) and b) associations between these chemicals and agricultural output with CMs using a geographical information system. In one of the three years during the sampling period (2008, 2009 or 2010) Cl-, dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethylene (p,p'-DDE), dichlorodiphenyldichloroethane (p,p'-DDD), and endosulfan levels were measured in 465 (465/736, 63%) catchment basins. Agricultural outputs for crops during 2006-2010 were also evaluated (t/km2). Further, CM kernel density for the 399 municipalities in Paraná during 2007-2014 was investigated. Cl- levels increased significantly in one of the three years (2008, 2009 or 2010) in western catchment basins, compared to 1996 (p < 0.0001). The municipalities were divided according to the obtained Cl- levels, where sub-region C2 (central-southern) < 1.8 mg/L ≤ sub-regions C1 (northern-western) and C3 (eastern-southern). We identified 8756 cases of CMs among 1,221,287 newborns (NB) in all sub-regions. C1 had higher DDT-DDE-DDD (p,p'-DDT + p,p'-DDE + p,p'-DDD) concentrations, agricultural output, and CM kernel density. C2 and C3 had minor agricultural outputs (per square kilometer) and CM densities. A 2.96 mg/L increase in Cl- between sub-regions C1 and C2 was co-localized with a 45% increase in CM density (spatial relative risk = 1.45, CI 95%: 1.36-1.55). C1 had the highest log likelihood ratios (p = 0.001) identified via SaTScan clustering analyses. Organochlorines and other toxic chlorinated chemicals may contribute to CMs in humans, and these chemicals are ultimately transformed and release Cl- in rivers. Higher Cl- levels were correlated significantly with higher agricultural productivity, DDT-DDE-DDD levels, and CMs in some parts of the northern and western sub-regions (C1).