Cancer family syndrome: cytogenetic investigations, in vitro tetraploidy, and biomarker studies in a large family.

Fifty-five members of a family with the cancer family syndrome (CFS) were investigated for the following potential biomarkers for cancer proneness: (1) cytogenetics of peripheral blood lymphocytes and skin fibroblasts; (2) in vitro tetraploidy of dermal fibroblast monolayer cultures; (3) quantitative serum immunoglobulin determinations; (4) study of genetic linkage with respect to eight blood group markers including Kidd. Biological specimens were obtained from 14 patients affected with cancer, 21 subjects at risk, and 20 healthy subjects. None of the markers tested in this family, in order to identify a biomarker for the status of CFS gene carrier, was found to be useful. Our search for linkage to other biological markers (DNA RFLPs and NK cells) is in progress.

Depressed level of natural killer cells in cancer family syndrome.

Individuals from kindred with cancer family syndrome (CFS) have an increased genetic risk for the development of adenocarcinoma of the colon as well as of several other organs. Previous studies have suggested that this high occurrence of adenocarcinoma in this as in other hereditary neoplastic syndromes may be correlated to an underlying abnormality in immunological tumor surveillance. In attempt to define a marker that might identify individuals within CFS kindred at risk of developing cancer, we determined natural killer (NK) cell number and NK cell function in affected and healthy members of a CFS family. We studied 13 cancer-affected patients, 20 unaffected but "at-risk" subjects, 20 healthy subjects and 26 normal individuals matched to the patients with colon cancer on the basis of sex and age. We determined the number of NK cells and their function concurrently, using a monoclonal antibody and a 51Cr-release assay with K562 as target cells. We found that the number of NK cells was significantly (P = 0.00004) reduced in cancer patients as compared with healthy subjects and normal controls. Of the 20 at-risk individuals 9 had levels lower than the norm, while 11 showed normal-values. Consequently, the mean percentage of NK cells of this group does not differ either from that of normal subjects or from that of cancer patients. Mean NK cell function was lower in cancer patients than in healthy members of the CFS family but the differences were not statistically significant. Therefore, the mean NK cell function per single cell, expressed as a ratio between cytotoxicity (LU) and the number of NK1-positive cells, resulted paradoxically in an increase when compared with that of normal subjects. The possible mechanisms for this dichotomy were examined.