Validating the Family History Scoring System application to identify Lynch syndrome families

Background

The FHSS (a points-based scoring system) was previously used to identify families at high risk of an inherited colorectal cancer syndrome. AM-I (Amsterdam-I) families scored high (≤12), but some scored low (≥8) when scored from unaffected relative’s perspective [1]. The FHSS is being applied to Lynch families (MMR+) and familial colon cancer type X (Type X) to see if the scoring system would yield similar results.

Method

Family members (1 proband, 2 siblings and 2 children of the sibling) in Lynch and Type X families identified from the Jagelman Registry database were scored according to the score sheet described in Table 1.

Table 1

They were scored from perspective of an affected proband (AP) or unaffected proband (UP), affected (AS) or unaffected (US) sibling or a child of each sibling (Child).

Results

91 probands (68 affected, 23 unaffected) in 48 AM-I, 14 Amsterdam-II (AM-II), 6 Amsterdam-Like (AM-Like), 10 Familial Colon Cancer (FCC), 6 no syndrome (syn) families and 7 Type X were scored. 197 relatives were scored (38 affected siblings, 23 Child AP/AS, 40 Child AP/US, 77 unaffected siblings, 9 Child UP/AS, 10 Child UP/US). AM-I and Type X median scores were higher than other syndromes (<12) and suggestive of HNPCC when scored from the perspective of the proband, sibling or child of AS. The median scores were lower in AM-II, FCC, AM-Like, and no syn families with fewer colon cancers (Table 2).

Table 2 Median Scores

Conclusion

Findings were similar to validation study conducted on AM-I families. The FHSS is a reliable tool to determine familial risk of colorectal cancer especially in AM-I families and depends on the perspective of person being scored. In small families, those with predominantly extra colonic cancers or high-risk polyps, or if affected relatives are more than a generation from an individual, the FHHS will not always identify high risk or Lynch families.