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.

hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer.

BACKGROUND: The aim of this study was to search for mutations in the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. RESULTS: Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. The hMLH1 gene had a higher mutation detection rate than hMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in the hMLH1 gene and four in the hMSH2 gene. CONCLUSIONS: The hMLH1 gene had a higher mutation detection rate than hMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.