CHING-HUNG LINShen C.-Y.JIH-HSIANG LEECHIUN-SHENG HUANGCHIH-HSIN YANGWEN-HUNG KUODWANG-YING CHANGHsiung C.-N.KUAN-TING KUOWEI-WU CHENI-CHUN CHENWu P.-F.SUNG-HSIN KUOChen C.-J.YEN-SHEN LUANN-LII CHENG2020-03-072020-03-0720151932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929353616&doi=10.1371%2fjournal.pone.0124908&partnerID=40&md5=200ce8d48c365545062110de0ca72745https://scholars.lib.ntu.edu.tw/handle/123456789/473553Background: 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. ? 2015 Lin et al.[SDGs]SDG3BIM protein; genomic DNA; apoptosis regulatory protein; BCL2L11 protein, human; BIM protein; membrane protein; oncoprotein; adult; age distribution; allele; Article; BIM gene; breast cancer; breast carcinogenesis; breast metastasis; cancer prognosis; cancer staging; cancer survival; cohort analysis; controlled study; disease association; East Asian; female; gene deletion; gene frequency; human; major clinical study; middle aged; overall survival; prevalence; Taiwan; wild type; age; aged; Asian continental ancestry group; Breast Neoplasms; cancer grading; case control study; Far East; genetic polymorphism; genetic predisposition; genetics; metastasis; mortality; pathology; prognosis; very elderly; young adult; Adult; Age Factors; Aged; Aged, 80 and over; Apoptosis Regulatory Proteins; Asian Continental Ancestry Group; Bcl-2-Like Protein 11; Breast Neoplasms; Case-Control Studies; Far East; Female; Genetic Predisposition to Disease; Humans; Membrane Proteins; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Polymorphism, Genetic; Prevalence; Prognosis; Proto-Oncogene Proteins; Sequence Deletion; Young Adultjournal article10.1371/journal.pone.0124908259091942-s2.0-84929353616