ABSTRACT
Breast cancer is the single largest cancer and causes the high rate of cancer mortality among women. A positive family history of breast cancer is recognized as one of the major risk factors for this disease. The present study evaluates bleomycin (BLM)-induced chromosome sensitivity analysis in breast cancer families which provides indirectly a measure of the DNA repair defect of each person. BLM sensitivity assay on cultured lymphocytes of 36 familial breast cancer patients, their 85 first or second degree female relatives, 36 sporadic breast cancer patients and 40 age- and sex-matched controls (without any family history of cancer) were carried out to measure interindividual variation in their DNA repair capacity through mutagen-induced chromosome sensitivity analysis. Fifty percent of familial breast cancer patients and seven unaffected relatives showed hypersensitivity. Compared to hyposensitive relatives these seven subjects may be considered as high risk individuals.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms/genetics , DNA Repair , Adolescent , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/pharmacology , Bleomycin/pharmacology , Chromatids/drug effects , Chromatids/metabolism , Chromosome Banding , Chromosomes, Human/drug effects , DNA Damage , DNA, Neoplasm/drug effects , DNA, Neoplasm/metabolism , Family Health , Female , G2 Phase/physiology , Humans , Individuality , Middle Aged , Risk Factors , S Phase/physiologyABSTRACT
Family history of colorectal cancer is recognized as a risk factor for the disease and the development of colorectal cancer represents a suitable model for illustrating multistep tumor development. Bleomycin induced chromosome sensitivity studies were done in 7 colorectal cancer families consisting of 12 colorectal cancer patients and their 34 first degree relatives and 12 sporadic colorectal patients for comparison and identification of high risk family members with genetic instability. All patients and 4 unaffected relatives showed increased bleomycin sensitivity, which might be due to defective DNA repair system. These four relatives may be classified as high risk (without cancer at present) individuals. The study is being continued in more number of familial colorectal cancer patients and their relatives to arrive at definite conclusions.
Subject(s)
Bleomycin/pharmacology , Colorectal Neoplasms/genetics , Family Health , Mutagenesis , Adult , Aged , Female , Humans , Male , Middle Aged , RiskABSTRACT
Pedigree analysis of the oral cancer (OC) patients registered at our Centre had disclosed familial aggregation of oral cancer which hitherto has not been largely reported. There is a paucity of information on the genetic determinism for familial oral cancer predisposition. Therefore, we investigated constitutional chromosome abnormalities and bleomycin-induced chromosome sensitivity of 7 familial and 10 sporadic oral cancer patients and 14 unaffected family members (first-degree relatives) to determine whether these factors could give any clues regarding cancer-predisposing factors. Neither the oral cancer patients nor the unaffected family members showed any constitutional chromosomal abnormalities. However, with regard to bleomycin sensitivity, there was significant difference between the oral-cancer patients and unaffected relatives. The mean b/c value was 1.68 +/- 0.48 for familial OC patients, 1.12 +/- 0.36 for sporadic OC patients and 0.52 +/- 0.18 for the unaffected family members (p < 0.001). A noteworthy observation was that one unaffected family member also showed bleomycin hypersensitivity and expressed a mean b/c value of 1.32, at the initiation of the study. That patient later developed oral carcinoma. This clearly demonstrates that mutagen hypersensitivity among unaffected relatives in OC families may be related to cancer predisposition. The mutagen sensitivity study is being continued in a larger series of subjects, for the development of a cytogenetic marker for prediction of cancer susceptibility.
