Risk for Hereditary Neoplastic Syndromes in Women with Mismatch Repair-Proficient Endometrial Cancer

Abstract

Endometrial cancer (EC) is a prevalent malignancy in women, and those who are proficient in the DNA mismatch repair (pMMR) pathway may have a family history (FH) that meets the criteria for a hereditary neoplastic condition (HNS). This study aimed to estimate the risk of HNS in women with pMMR endometrial tumors by analyzing their FH. To achieve this, we collaborated with a primary study and collected FH information by telephone. The final sample comprised 42 women who responded to the Primary Screening Questionnaire. Their family pedigrees were drawn and categorized according to internationally standardized criteria for the risk of HNS. Results showed that 26 women (61%) were found to be at risk for HNS, with Bethesda criteria being met by 23%, Amsterdam criteria by 15%, and 4% met the attenuated familial adenomatous polyposis criteria. Our results emphasize the importance of FH and the need to encourage healthcare professionals to collect and document FH more frequently, even if it is self-reported. By identifying individuals with HNS, we can improve their outcomes and reduce the burden of cancer in families with a predisposition to cancer.

Keywords: family history; lineage; patterns of inheritance; risk; uterine neoplasms.

Figure 1

Workflow depicting the primary study’s casuistry (n = 127), the current study’s (n = 58), and the composition of our final sample (n = 42). The diagram also showcases the distribution of samples meeting the criteria for each listed HNS, with the acknowledgment that a single sample may fall under multiple syndrome criteria [16].

Figure 2

Pedigree example of a proband with two primary cancers.