Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in Argentina: Report from a Referral Hospital Register

Abstract

PURPOSE: The first Argentine experience with epidemiologic, molecular, and genetic counseling data is reported. METHODS: We analyzed 43 families fulfilling Amsterdam criteria identified from a prospective database with data from 779 relatives. RESULTS: Eleven families (25.6 percent) presented as Lynch I, 29 (67.4 percent) as Lynch II, and 3 (7 percent) as Muir-Torre syndrome. Among the 306 affected members, 197 cases of colorectal cancer were identified (mean age at diagnosis, 52.1 (range, 21-90) years). The most frequent extracolonic tumors were gastric adenocarcinoma in males and endometrium adenocarcinoma in females. A high incidence of breast cancer was observed (16 cases among 155 females, crude rate: 11,594.20/100,000). Twenty-seven patients (8.8 percent) developed more than one tumor. These patients were younger than those with only one tumor (45 vs. 51 years; P=0.001). In 5 of 11 patients who underwent molecular sequencing, a pathologic mutation was found. A novel C deletion at 1910 nucleotide, codon 637, exon 12 of MSH2 gene was identified in a family with a strong aggregation of breast cancer with lack of MSH2 immunohistochemical staining. For 78.2 percent of counseled individuals, this session represented the first time they received information, and 73.9 percent stated that their physicians were unaware of their family background. CONCLUSIONS: Argentine families presented a high incidence of stomach cancer. The elevated incidence of breast cancer and its association with a novel hMSH2 mutation bring to consideration the inclusion of this malignancy as part of the syndrome. A lack of awareness by both physicians and persons at risk was observed. [

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome

“…A study of South American LS families from Brazil (101 families), Argentina (16 families) and Uruguay (6 families), demonstrated that 56.3% of the MMR mutations were found on the MLH1 gene [28]. In contrast, a different report of 43 unrelated Argentinian families that fulfill Amsterdam criteria, for which 5 mutations were encountered, most of these were found at the MSH2 gene, similar to our Caribbean Hispanics [35]. Differences in the spectrum of MMR mutations between Hispanic populations could be due to differences in the, sample size, selection bias, as well as, genetic ancestry of the individual populations.…”

Mutation spectrum in South American Lynch syndrome families

“…The mutation spectrum is predominated by MLH1 (60%) and MSH2 (40%) mutations [3,19-22], but the seemingly larger contribution than the 42% and 33% reported in the InSIGHT database could reflect failure to test for MSH6 and PMS2 mutations in most South American studies [1]. Referral bias in populations that have more recently been screened for mutations represents a potential limitation, but the strong contribution from MLH1 and MSH2 could also reflect population structure [2,4,5,7]. Frameshift mutations and nonsense mutations were the most common types of mutations, which are in agreement with findings from other populations [1,23-26], with hotspots in exons 16 and 18 of MLH1 and in exon 13 of MSH2 (Figure 2b).…”

“…In Chile, Colombia, Peru and Bolivia, Spanish colonist and American Indian ancestry influence the populations [2,3]. Mutation screening in South American families suspected of Lynch syndrome has identified disease-predisposing germline mutations in MLH1 and MSH2 in 16-45% of families that fulfill the Amsterdam criteria and/or the Bethesda guidelines [2-7]. Hereditary colorectal cancer registries have been established in Argentina, Brazil, Uruguay and Chile with the aim to collect and share data on the MMR gene mutation spectrum, identify potential founder mutations, interpret the role of unclassified genetic variants and to study cancer risks in the South American Lynch syndrome population.…”

Hereditary cancer syndromes in Latino populations: genetic characterization and surveillance guidelines

“…In a review published by Dominguez-Valentín et al, the LS mutation spectrum in South American countries was described [62]. Pathogenic mutations in the MMR genes were identified in patients from Brazil [53], Argentina [63], Uruguay [64], and Colombia [65] (Table 3). Furthermore, the InSIGHT database contains additional information on MMR mutations in additional Hispanic subpopulations, Portugal, and Spain [53].…”