Abstract
The chromosomal fragility of peripheral blood lymphocytes from 50 women, undergoing operations for breast tumors (47 carcinomas, 2 intraductal papillomatoses and 1 malignant lymphoma) was studied to ascertain the association between chromosome fragility and epidemiologic data, such as a family or personal history of cancer, hormonal status, etc. Under conditions of folic acid and thymidine depletion, the average number of gaps and breaks on the patients' lymphocyte chromosome was 6.02±5.28 and that in the control medium was 2.0±2.0 while those of healthy controls were 5.8±5.5 and 1.36±1.22. These gaps and breaks were mostly seen in group A chromosomes (4.1±2.6) in 24 patients, including the 2 with benign tumors and the 1 with the lymphoma as well as 11 healthy controls. They were frequent in group B (3.0±0) in 3 patients, in group C (4.3±2.9) in 11 patients, and in groups D (2.0±1.0) and E (3.0±1.0) in 3 patients from each. This different distribution of gaps and breaks correlated neither with the patients' age nor with their tumor's histology, but patients having a late menarche were distributed in non‐A groups. There was low inducibility of breaks in patients with a family history of breast cancer and/or relatively rare cancers. The availability of common fragile sites for studying an individual's susceptibility to cancer is discussed. One patient showed a bromodeoxyuridine‐requiring heritable 10q25 fragile site. Another, with triple primary cancers, showed a constitutional translocation of t(5;19)(q15;q13).
Keywords: Breast cancer, Chromosome fragility, Epidemiology
Full Text
The Full Text of this article is available as a PDF (325.7 KB).
References
- 1).Lynch , H. T. , Albano , W. A. , Heieck , J. J. , Mulcahy , G. M. , Lynch , J. F. , Layton , M. A. and Danes , B. S.Genetics, biomarkers, and control of breast cancer: a review . Cancer Genet. Cytogenet. , 13 , 43 – 92 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 2).Miller , A. B. and Bulbrook , R. D.Multidisciplinary project on breast cancer: the epidemiology, aetiology and prevention of breast cancer . Int. J. Cancer , 37 , 173 – 177 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 3).Livingston , G. K. , Cannon , L. A. , Bishop , D. T. , Johnson , P. and Fineman , R. M.Sister chromatid exchange: variation by age, sex, smoking, and breast cancer status . Cancer Genet. Cytogenet. , 9 , 289 – 299 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 4).Dekaban , A.Persisting clone of cells with an abnormal chromosome in a woman previously irradiated . J. Nucl. Med. , 6 , 740 – 746 ( 1965. ). [PubMed] [Google Scholar]
- 5).Lejeune , J. , Dutrillaux , B. , Lafourcade , J. , Berger , R. , Abonyi , D. and Rethore , M. O.Endoreduplication selective du bras long du chromosome 2 chez une femme et sa fille . C. R. Acad. Sci. , 266 , 24 – 26 ( 1968. ). [PubMed] [Google Scholar]
- 6).Sutherland , G. R.Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culure . Am. J. Hum. Genet. , 31 , 125 – 135 ( 1979. ). [PMC free article] [PubMed] [Google Scholar]
- 7).Le Beau , M. M.Chromosomal fragile sites and cancer‐specific rearrangements . Blood , 67 , 849 – 858 ( 1986. ). [PubMed] [Google Scholar]
- 8).Yunis , J. J. and Soreng , A. L.Constitutive fragile sites and cancer . Science , 226 , 1199 – 1204 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 9).Yunis , J. J. , Soreng , A. L. and Bowe , A. E.Fragile sites are targets of diverse mutagens and carcinogens . Oncogens , 1 , 59 – 69 ( 1987. ). [PubMed] [Google Scholar]
- 10).Takahashi , E. , Hori , T. and Murata , M.Distamycin A‐induced fragility on chromosome 16, fra(16)(q22), in a Japanese population . Proc. Jpn. Acad. , 61B , 299 – 302 ( 1985. ). [Google Scholar]
- 11).Takahashi , E. , Hori , T. and Murata , M.A BrdU‐requiring fragile site, fra(10)(q25), in a Japanese population . Proc. Jpn. Acad. , 61B , 165 – 168 ( 1985. ). [Google Scholar]
- 12).Lynch , H. T. , Albano , W. A. , Danes , B. S. , Layton , M. A. , Kimberling , W. J. , Lynch , J. F. , Cheng , S. C. , Costello , K. A. , Mulcahy , G. M. and Wagner , C. A.Genetic predisposition to breast cancer . Cancer , 53 ( No. 3 Suppl. ), 612 – 622 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 13).Lidereau , R. , Escot , C. , Theillet , C. , Champene , M. H. , Brunet , M. , Gest , J. and Callahan , R.High frequency of the human c‐Ha‐ras‐1 proto‐oncogene in breast cancer patients . J. Natl. Cancer Inst. , 77 , 697 – 701 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 14).Berger , R. , Bernheim , A. , Kristoffersson , U. , Mitelman , F. and Olsson , H.C‐band heteromorphism in breast cancer patients . Cancer Genet. Cytogenet. , 18 , 37 – 42 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 15).Kivi , S. and Mikelsaar , A. V.Polymorphism of AG‐stained nucleolus organizer regions in lymphocytes of patients with ovarian or breast adenocarcinoma . Hum. Genet. , 69 , 350 – 352 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 16).Rodgers , C. S. , Hill , S. M. and Halten , M. A.Cytogenetic analysis in human breast carcinoma, I. Nine cases in diploid range investigated using direct preparations . Cancer Genet. Cytogenet. , 13 , 95 – 119 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 17).Pathak , S. and Goodacre , A.Specific chromosome anomalies and predisposition to human breast, renal cell and colorectal carcinoma . Cancer Genet. Cytogenet , 19 , 29 – 36 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 18).Shabtai , F. , Klar , D. , Schwartz , A. , Moroz , A. and Halbrecht , I.Marker chromosomes in a family with high incidence of cancer . Cancer Genet. Cytogenet. , 11 , 281 – 287 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 19).Sutherland , G. R.Heritable fragile sites on human chromosomes. IX. Population cytogenetics and segregation analysis of the BrdU‐requiring fragile site at 10q25 . Am. J. Hum. Genet. , 34 , 753 – 756 ( 1982. ). [PMC free article] [PubMed] [Google Scholar]
- 20).Sanfilippo , S. , Neri , G. , Tedeschi , B. , Carlo‐Stella , N. , Triolo , O. and Serra , A.Chromosomal fragile sites: preliminary data of a population survey . Clin. Genet. , 24 , 295 ( 1983. ). [Google Scholar]
- 21).Takahashi , E. , Hori , T. and Murata , M.Population cytogenetics of rare fragile sites in Japan . Hum. Genet. , 78 , 121 – 126 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 22).Dubé , I. D. , Raimondi , S. C. , Pi , D. and Kolousek , D. K.A new translocation, t(10;14)(q24;q11), in T cell neoplasia . Blood , 67 , 1181 – 1184 ( 1986. ). [PubMed] [Google Scholar]
- 23).Krivit , W. and Good , R. A.Simultaneous occurrence of mongolism and leukaemia . J. Dis. Child , 94 , 289 – 290 ( 1957. ). [DOI] [PubMed] [Google Scholar]
- 24).Stewart , A. , Webb , J. and Hewitt , D.A survey of childhood malignancies . Br. Med. J. , i , 1495 – 1508 ( 1958. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25).Holland , W. W. , Doll , R. and Carter , C. O.The mortality from leukaemia and other cancers among patients with Down's syndrome (Mongols) and among their parents . Br. J. Cancer , 16 , 177 – 186 ( 1962. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26).Harnden , D. G. , Maclean , N. and Langlands , A. O. , Carcinoma of the breast and Klinefelter's syndrome . J. Med. Genet. , 8 , 460 – 461 ( 1971. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27).Scheike , O.Male breast cancer . Acta Pathol. Microbiol. Scand. Suppl , 251 , 3 – 35 ( 1975. ). [PubMed] [Google Scholar]
- 28).Blattner , W. A. , Kistenmacher , M. L. , Tsai , S. , Punnett , H. H. and Giblett , E. R.Clinical manifestations of familial 13;18 translocation . J. Med. Genet. , 17 , 373 – 379 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29).Harnden , D. G. , Langslands , A. O. , Mcbeath , S. , O'Riordan , M. and Faed , M. J. W.The frequency of constitutional chromosome abnormalities in patients with malignant disease . Eur. J. Cancer , 5 , 605 – 614 ( 1969. ). [DOI] [PubMed] [Google Scholar]
