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. 2022 Jun 19;14(12):3014.
doi: 10.3390/cancers14123014.

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

Viviane K Q Gerber  1   2   3 , Mariana M Paraizo  1 , Humberto C Ibañez  1 , José C Casali-da-Rocha  4   5   6 , Emilia M Pinto  7 , Diancarlos P Andrade  1   2 , Marilea V C Ibañez  1 , Heloisa Komechen  1   8 , Mirna M O Figueiredo  8 , Gislaine Custódio  8 , Carmem M C M Fiori  9 , José H G Balbinotti  1 , Jeanine M Nardin  4 , Thais A Almeida  4 , Olair O Beltrame  4 , Paula A Yamada  4 , Gabriel S de Fraga  4 , Lucas L de Brito  4 , Jamylle Martins  4 , Viviane S Melanda  10 , Otavio A B Licht  11 , Victoria Z Teixeira  3 , Sandy K S Pinho  3 , Silvia Bottini  12 , Enzo Lalli  13 , Gerard P Zambetti  7 , Bonald C Figueiredo  1   2   8
Affiliations

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

Viviane K Q Gerber et al. Cancers (Basel). .

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.

Keywords: TP53 p.R337H; XAF1 p.E134*; breast cancer; environment; pesticides.

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Conflict of interest statement

The authors have no conflict of interest to disclose.

Figures

Figure 1
Figure 1
BC-free probabilities among TP53 p.R337H carriers and noncarriers (Group 1). Censoring (vertical line) is indicated by vertical marks. BC occurrences in three generations (last two or three were grouped as the third generation) are shown in panels (A–C). Panel (D) (grouping all generations) shows younger age of BC among p.R337H carriers than noncarriers.
Figure 2
Figure 2
Breast cancer age-specific mortality rate (2005–2015) per 100,000 women over 30 years of age (Group 2). C0 was not evaluated.
Figure 3
Figure 3
Mean (red dots) and median (vertical lines) BMIs are shown in boxplots. Estimated marginal means from a linear model (analysis of variance) detected lower and upper confidence limits (CL), and the p values between two subregions (contrast). SE, standard error; df, degree of freedom.
See this image and copyright information in PMC

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