Frequency of extracolonic tumors in Brazilian families with Lynch syndrome: analysis of a hereditary colorectal cancer institutional registry

Abstract

Lynch syndrome (LS) is caused by inherited germline mutations in mismatch repair (MMR) genes. It is one of the commonest forms of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is characterized by early age of onset, with a tendency for multiplicity and an increased risk for extra-colonic tumors at particular sites. In this study we have evaluated the frequency of extra-colonic tumors in 60 unrelated LS families fulfilling the Amsterdam criteria (ACI. ACII) from the Oncotree database of the Hereditary Colorectal Cancer Registry of the AC Camargo Hospital. All families' pedigree was extensively analyzed, varying from 2 to 6 generations with a total of 2,095 individuals evaluated. As expected, colorectal cancer was the most frequent tumor in the families (334 cases). We found 200 extracolonic tumors among all individuals with a higher ratio in women (123 cases) than men (77 cases). By far, breast cancer (32 cases) was the most frequent extracolonic manifestation in women followed by endometrial (20 cases) and uterine cervix cancer (20 cases). For man, prostate (16 cases) and stomach (12 cases) cancer were the most frequent extracolonic tumors. It is well know that establishing the diagnosis is challenging and requires knowledge and surveillance. Thus, recognition of individuals and families with hereditary predisposition to cancer according to clinical and molecular features, combined with intensive surveillance and management programs, can contribute substantially to improve results related to the diagnosis and characterization of LS.

Epidemioclinical Feature of Early-Onset Colorectal Cancer at-Risk for Lynch Syndrome in Central Iran

“…Meanwhile, there are significant discrepancies, 33-78%, between similar studies in other countries (Park et al, 2000;Maul et al, 2006;da Silva et al, 2010;Bansidhar, 2012).…”

“…There are, however, distinct discrepancies between Western and Eastern populations over this issue (Bansidhar, 2012). In a Brazilian study, GC was the second most common extracolonic cancer in HNPCC families (da Silva et al, 2010). In addition, several Chinese and Korean studies have presented GC as the most common extracolonic cancer in HNPCC (Park et al, 2000), while in Western populations, the prevalence of GC within HNPCC cohorts is the third or fourth most common cancer (Maul et al, 2006;Bansidhar, 2012).…”

Colorectal cancer in the young, many questions, few answers

“…In the Lynch Syndrome, tumours have been known to be predominant in the proximal colon [35,36] , but recent research revealed contradictory data where the most frequent site among early onset CRC patients was the distal colon [37] . Of these, between 40 and 60 percent were in the rectum [38,39] .…”

Risk of Prostate Cancer in Lynch Syndrome: A Systematic Review and Meta-analysis

“…Attempts have been made to directly estimate the risk of prostate cancer in Lynch syndrome using studies of cancer history of men from Lynch syndrome families (14,15,19,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). These studies have generally been limited in terms of size and analytic methods used, so as a consequence, estimates are imprecise and inconsistent.…”