Abstract
Lynch syndrome (LS) is a dominantly inherited condition with incomplete penetrance, characterized by high predisposition to colorectal cancer (CRC), endometrial and ovarian cancers, as well as to other tumors. LS is associated with constitutive DNA mismatch repair (MMR) gene defects, and carriers of the same pathogenic variants can show great phenotypic heterogeneity in terms of cancer spectrum. In the last years, human gut microbiota got a foothold among risk factors responsible for the onset and evolution of sporadic CRC, but its possible involvement in the modulation of LS patients’ phenotype still needs to be investigated. In this pilot study, we performed 16S rRNA gene sequencing of bacterial DNA extracted from fecal samples of 10 postoperative LS female patients who had developed colonic lesions (L-CRC) or gynecological cancers (L-GC). Our preliminary data show no differences between microbial communities of L-CRC and L-GC patients, but they plant the seed of the possible existence of a fecal microbiota pattern associated with LS genetic background, with Faecalibacterium prausnitzii, Parabacteroides distasonis, Ruminococcus bromii, Bacteroides plebeius, Bacteroides fragilis and Bacteroides uniformis species being the most significantly over-represented in LS patients (comprising both L-CRC and L-GC groups) compared to healthy subjects.
Highlights
Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, conferring a high lifetime risk of colorectal cancer (CRC), endometrial cancer (EC), ovarian cancer (OC), as well as of a number of other neoplasms
When LS is assessed on the basis of personal and/or familial history of cancer, MSH2 and MLH1 germline lesions are found in the great majority of patients, with MSH6 and PMS2 germline defects only accounting for a minority of cases (Boland et al, 2018)
The taxonomic composition identified in our healthy subjects and LS patients (L-gynecological cancer only (GC) and L-CRC) reflects a microbial community typical of the intestinal microbiota
Summary
Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, conferring a high lifetime risk of colorectal cancer (CRC), endometrial cancer (EC), ovarian cancer (OC), as well as of a number of other neoplasms. LS accounts for 3% of CRC and for 2% of EC cases, with a recently estimated prevalence of 1:279 in the general population (Win et al, 2017). When LS is assessed on the basis of personal and/or familial history of cancer, MSH2 and MLH1 germline lesions are found in the great majority of patients (up to 87%), with MSH6 and PMS2 germline defects only accounting for a minority of cases (Boland et al, 2018). LS patients show great phenotypic heterogeneity, including tumor spectrum and age of onset, even among family members sharing the same mutation (Scott et al, 2001)
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