High Prevalence of the BIM Deletion Polymorphism in Young Female Breast Cancer in an East Asian Country

PLoS One. 2015 Apr 24;10(4):e0124908. doi: 10.1371/journal.pone.0124908. eCollection 2015.

Abstract

Background: A rapid surge of female breast cancer has been observed in young women in several East Asian countries. The BIM deletion polymorphism, which confers cell resistance to apoptosis, was recently found exclusively in East Asian people with prevalence rate of 12%. We aimed to evaluate the possible role of this genetic alteration in carcinogenesis of breast cancer in East Asians.

Method: Female healthy volunteers (n = 307), patients in one consecutive stage I-III breast cancer cohort (n = 692) and one metastatic breast cancer cohort (n = 189) were evaluated. BIM wild-type and deletion alleles were separately genotyped in genomic DNAs.

Results: Both cancer cohorts consistently showed inverse associations between the BIM deletion polymorphism and patient age (≤35 y vs. 36-50 y vs. >50 y: 29% vs. 22% vs. 15%, P = 0.006 in the consecutive cohort, and 40% vs. 23% vs. 13%, P = 0.023 in the metastatic cohort). In healthy volunteers, the frequencies of the BIM deletion polymorphism were similar (13%-14%) in all age groups. Further analyses indicated that the BIM deletion polymorphism was not associated with specific clinicopathologic features, but it was associated with poor overall survival (adjusted hazard ratio 1.71) in the consecutive cohort.

Conclusions: BIM deletion polymorphism may be involved in the tumorigenesis of the early-onset breast cancer among East Asians.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / genetics*
  • Asia, Eastern / epidemiology
  • Asian People / genetics*
  • Bcl-2-Like Protein 11
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Polymorphism, Genetic*
  • Prevalence
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Sequence Deletion*
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Membrane Proteins
  • Proto-Oncogene Proteins

Grants and funding

This study was supported by grants from the National Taiwan University, Taiwan (grant number: NTU-ICRP-103R7557, URL: (http://irice-ca.mc.ntu.edu.tw/ aboutICECR.php), and the National Center of Excellence for Clinical Trial and Research, Taiwan (grant DOH102-TD-B-001, URL: (http://www.mohw.gov.tw/CHT/TDU/DM1_P.aspx?f_list_no=740&fod_list_no=0&doc_no=29307). ALC received the grants mentioned above. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.