The APC I1307K allele and breast cancer risk (original) (raw)

The I1307K variant of APC occurs in approximately 6% of Ashkenazi Jews and has been associated with familial colorectal neoplasia. In four of the eight pedigrees characterized by Laken et al.1, women who may be heterozygous for this allele were diagnosed with breast cancer. Animal models suggest a relationship between Min, a mutant allele of the mouse Apc gene, and breast neoplasia, with approximately 5% of B6 Min/+ females reported to develop breast tumours2. Loss of heterozygosity or comparative genomic hybridization studies have identified 5q or the APC region as sites of loss in both _BRCA1_-mutated and BRCA1 wild-type breast tumours3,4,5,6, suggesting a possible role for APC in the progression of a subset of breast tumours. We speculated that Ashkenazi Jewish women with breast cancer may be more likely to have the I1307K allele than unaffected Ashkenazi Jewish controls.

We determined the frequency of this polymorphism in 632 unrelated women with primary invasive breast cancer who were not selected for a family history of breast or ovarian cancer, and who self-reported as being of Ashkenazi Jewish descent. Cases were diagnosed at three centres: 216 in Toronto, 215 in New York (Memorial Sloan-Kettering Cancer Center (MSKCC)) and 201 in Montreal (SMBD-Jewish General Hospital). The Montreal cases were all diagnosed before age 65, whereas 73 of the 215 MSKCC cases were diagnosed before age 42. The remainder of the 632 cases were unselected for age. For 115 of the MSKCC cases, and all Montreal cases, the field for religion on the medical chart was used to select self-identified individuals of Jewish religion with breast tumour tissue available for study. Paraffin blocks were obtained and analysed anonymously. In 100 cases at MSKCC and all cases at Toronto, questionnaires were used to determine religious and geographical background from individuals with personal histories of breast cancer, irrespective of whether they had a family history of the disease. DNA was obtained from peripheral lymphocytes for these samples.

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Acknowledgements

We are grateful to L. Norton, J. Garber, C. Lerman, L. Petrukhin, S. Narod, H. Ostrer and T. Rebbeck. K.N. is supported by NIH training grant 1TG32GM08638, B.W. is supported by NIH RO1 CA5760 and the Breast Cancer Research Foundation. S.L.N. is supported by NIH RO1-CA74415 and DAMD-17-94-J4260. Study funding: National Institutes of Health (CA63720), the Society of Memorial Sloan-Kettering, the Breast Cancer Research Foundation, the Lymphoma Foundation, Fonds de la recherche en santé du Québec, the Judy Steinberg Research Fund, the National Cancer Institute of Canada, the Canadian Cancer Society and the Canadian Breast Cancer Research Initiative, as well as resources made available by the Cooperative Family Registry for Breast Cancer Studies, supported by NIH UO1 CA69467-01.

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Author notes

1. Trevor Woodage and Lawrence C. Brody: Genetics and Molecular Biology Branch, NHGRI, NIH , Bethesda, Maryland, USA. M.R., K.C.N., Z.Q.Y. and S.L.N. contributed equally to this work.

Authors and Affiliations

1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital ,
   Mark Redston, Hilmi Ozcelik, Irene Andrulis & Steven Gallinger
2. Ontario Cancer Genetics Network,
   Mark Redston, Hilmi Ozcelik, Irene Andrulis, Steven Gallinger & Ellen Warner
3. Sunnybrook Regional Cancer Centre,
   Ellen Warner
4. Centre for Research in Women's Health, University of Toronto, Ontario, Canada
   John Abrahamson
5. Departments of Human Genetics, Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
   Jaya Satagopan, Diana Yang, Doudja Nafa & Kenneth Offit
6. Departments of Medicine, Cancer Prevention Research Unit, SMBD-JGH, Oncology, Surgery, Human Genetics and Montreal General Hospital Research Institute, McGill University, Montreal, Quebec , Canada
   Zhi Qiang Yuan, Nora Wong, Leonard Pinsky & William Foulkes
7. Departments of Medicine and Genetics, Stellar-Chance Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania, USA
   Katherine L. Nathanson, Danielle Antin-Ozerkis & Barbara Weber
8. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
   Mary Daly & Andrew Godwin
9. Department of Medical Informatics, Genetic Epidemiology Group, University of Utah School of Medicine, Salt Lake City, Utah, USA
   Susan L. Neuhausen
10. Dana Farber Cancer Center, Boston, Massachusetts, USA
    Deborah Schrag
11. Children's Hospital, University of California at San Diego, California, USA
    Michael Kaback
12. Department of Genetics, University of Washington, Seattle, Washington, USA
    Mary-Claire King

Authors

1. Mark Redston
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2. Katherine L. Nathanson
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3. Zhi Qiang Yuan
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4. Susan L. Neuhausen
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5. Jaya Satagopan
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6. Nora Wong
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7. Diana Yang
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8. Doudja Nafa
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9. John Abrahamson
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10. Hilmi Ozcelik
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11. Danielle Antin-Ozerkis
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12. Irene Andrulis
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13. Mary Daly
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14. Leonard Pinsky
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15. Deborah Schrag
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16. Steven Gallinger
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17. Michael Kaback
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18. Mary-Claire King
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19. Trevor Woodage
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20. Lawrence C. Brody
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21. Andrew Godwin
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22. Ellen Warner
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23. Barbara Weber
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24. William Foulkes
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25. Kenneth Offit
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Corresponding author

Correspondence toWilliam Foulkes.

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Redston, M., Nathanson, K., Yuan, Z. et al. The APC I1307K allele and breast cancer risk.Nat Genet 20, 13–14 (1998). https://doi.org/10.1038/1666

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• Issue Date: September 1998
• DOI: https://doi.org/10.1038/1666