title: Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): a pilot study.
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 H(64) in breast cancer and explain, in part, the noted racial disparity, thus providing a novel target for diagnosis and treatment.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Balan
authors.forename: Pratima
authors.initials: P
authors.lastname: Nangia-Makker
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Larry
authors.initials: L
authors.lastname: Tait
authors.forename: Victor
authors.initials: V
authors.lastname: Hogan
authors.forename: Tirza
authors.initials: T
authors.lastname: Raz
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zeng Quan
authors.initials: ZQ
authors.lastname: Yang
authors.forename: Gen Sheng
authors.initials: GS
authors.lastname: Wu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guo
authors.forename: Huixiang
authors.initials: H
authors.lastname: Li
authors.forename: Judith
authors.initials: J
authors.lastname: Abrams
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Wilma L
authors.initials: WL
authors.lastname: Lingle
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ethier
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tainsky
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000235:genetics; D001213:Asian / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D037502:Galectin 3 / Q000235:genetics*; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008969:Molecular Sequence Data; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D037502:Galectin 3