Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): A pilot study

Vitaly Balan, Pratima Nangia-Makker, Ann G. Schwartz, Suk Jung Young, Larry Tait, Victor Hogan, Tirza Raz, Yi Wang, Quan Yang Zeng, Sheng Wu Gen, Yongjun Guo, Huixiang Li, Judith Abrams, Fergus J Couch, Wilma L. Lingle, Ricardo V. Lloyd, Stephen P. Ethier, Michael A. Tainsky, Avraham Raz

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Abstract

For reasons largely unknown, Caucasian women are at a significantly higher risk of developing breast cancer than Asian women. Over a decade ago, mutations in BRCA1/2 were identified as genetic risk factors; however, the discovery of additional breast cancer genes and genes contributing to racial disparities are lacking. We report a functional germline mutation (polymorphism) in the galectin-3 gene at position 191 (rs4644) substituting proline with histidine (P64H), which results in susceptibility to matrix metalloproteinase cleavage and acquisition of resistance to drug-induced apoptosis. This substitution correlates with incidence of breast cancer and racial disparity. Genotype analysis of 338 Caucasian (194 disease free and 144 breast cancer patients) and 140 Asian (79 disease free and 61 breast cancer patients) women showed that the allele homozygous for H64 exists in disease free Caucasian and Asian women at a frequency of 12% and 5%, respectively, versus 37% and 82% in breast cancer patients. The data indicate that H/H allele is associated with increased breast cancer risk in both races. The data implicate galectin-3 H64 in breast cancer and explain, in part, the noted racial disparity, thus providing a novel target for diagnosis and treatment.

Original languageEnglish (US)
Pages (from-to)10045-10050
Number of pages6
JournalCancer Research
Volume68
Issue number24
DOIs
StatePublished - Dec 15 2008

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Balan, V., Nangia-Makker, P., Schwartz, A. G., Young, S. J., Tait, L., Hogan, V., Raz, T., Wang, Y., Zeng, Q. Y., Gen, S. W., Guo, Y., Li, H., Abrams, J., Couch, F. J., Lingle, W. L., Lloyd, R. V., Ethier, S. P., Tainsky, M. A., & Raz, A. (2008). Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): A pilot study. Cancer Research, 68(24), 10045-10050. https://doi.org/10.1158/0008-5472.CAN-08-3224