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Increased constitutional chromosome sensitivity to bleomycin in patients with hereditary non polyposis colorectal cancer (HNPCC)

100%

Kladny J., Zajaczek S., Lubinski J.

Journal of Applied Genetics

1996

vol. 37

issue 4

385-392

It has been suggested that mutagen sensitivity is a constitutional factor which may be useful in identification of patients with an increased risk for the development of tumors. In this study, the chromosome sensitivity to bleomycin was measured according to HSU in patients with hereditary non polyposis colorectal cancer (HNPCC), sporadic colorectal cancer and in control persons with no tumor history in family. In vitro lymphocytes were exposed to bleomycin according to HSU and chromosomal damage was quantified by scoring breaks of 100 cells. A significant difference (P < 0.01) in the mean number of breaks per cell (b/c) was found between HNPCC patients (0.59_0.14; n = 12; mean age 55.4 yrs) and control individuals (0.35_0.13: n = 12; mean age 55.8 yrs). In contrast, patients with sporadic colorectal cancer showed a mean b/c value of 0.43_0.14 (n = 14; mean age 63.4 yrs) which was not significantly higher than that in control individuals for this group (0.42 _0.15; n = 14; mean age 63.1 yrs). Selenium protected lymphocytes of HNPCC patients against bleomycin activity in vitro.

Age at diagnosis of cancer as predictor of mutation occurrence in families suspected of HNPCC

76%

Kurzawski G., Debniak D. T., Debniak T., Kladny K. J., Kladny J., Lubinski L. J., Lubinski J.

Journal of Applied Genetics

2001

vol. 42

issue 3

359-366

Analysis of significance of age at cancer diagnosis as a factor allowing identification of a subgroup of patients with a high frequency of hMSH2 and hMLH1 mutations among families that fulfil suspected HNPCC criteria was performed. DNA from thirty-one unrelated patients affected by colorectal cancer from families matching the above criteria were studied by direct sequencing for occurrence of hMSH2 and hMLH1 gene mutations. Seven unequivocal constitutional mutations were detected: five in the hMLH1 gene and two in the hMSH2 gene. Additionally, one hMLH1 alteration of unknown significance was found. All seven mutations were found in a subgroup of 19 patients with cancer diagnosed before the age of 50 years. In a subgroup of 12 patients with cancer diagnosed at an older age only one case with hMLH1 alteration of unknown significance was detected. Our results indicate that early age at cancer diagnosis seems to be a crucial pedigree factor in discrimination of patients with hMSH2 or hMLH1 mutations among families suspected of HNPCC and matching criteria I of ICG-HNPCC.

Hereditary tumors - prophylactics, early diagnosis, treatment

52%

Lubinski J., Zajaczek S., Kladny J., Kurzawski G., Menkiszak J., Hadaczak P., Cybulski C., Krzystolik K., Toloczko A., Podolski J., Gro

Biotechnologia

1996

issue 4

201-207

The authors describe the major rules of prophylactics, survaillance and treatment in patients with high hereditary predispodition for tumors on the basis of the experience of the first Polish hereditary cancer center, which was established in Szczecin in 1992.

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2 Journal of Applied Genetics

1 Biotechnologia

1 2001

2 1996

3 Kladny J.

3 Lubinski J.

2 Kurzawski G.

2 Zajaczek S.

1 Cybulski C.

1 Debniak D. T.

1 Debniak T.

1 Gro

1 Hadaczak P.

1 Kladny K. J.

1 Krzystolik K.

1 Lubinski L. J.

1 Menkiszak J.

1 Podolski J.

1 Toloczko A.

Search results

Increased constitutional chromosome sensitivity to bleomycin in patients with hereditary non polyposis colorectal cancer (HNPCC)

Age at diagnosis of cancer as predictor of mutation occurrence in families suspected of HNPCC

Hereditary tumors - prophylactics, early diagnosis, treatment