BCL2-like 11 intron 2 deletion polymorphism is not associated with non-small cell lung cancer risk and prognosis.
OBJECTIVE
BCL2-Like 11(BIM), which encodes a BH3-only protein, is a major pro-apoptotic molecule that facilitates cell death. We hypothesized that a BIM intron 2 deletion polymorphism increases lung cancer risk and predicts poor prognosis in non-small lung cancer (NSCLC) patients.


METHODS
We prospectively recruited 450 lung cancer patients and 1:1 age, sex, and smoking status matched control subjects from February 2013 to April 2014 among patients treated at Severance, Gangnam Severance, and Chonnam Hwasoon Hospital. The presence of a 2903-bp genomic DNA deletion polymorphism of intron 2 of BIM was analyzed by PCR and validated by sequencing. Odds ratios were calculated by chi-square tests and survival analysis with Kaplan-Meier estimation.


CONCLUSIONS
Sixty-nine out of 450 (15.3%) lung cancer patients carried the BIM deletion polymorphism, while 66 out of 450 (14.7%) control subjects carried the BIM deletion polymorphism, with an odds ratio of for lung cancer of 1.054 (95% CI; 0.731-1.519). We categorized 406 NSCLC patients according to the presence of the polymorphism and found that there were no statistically significant differences in age, sex, histologic type, or stage between subjects with and without the deletion polymorphism. The BIM deletion polymorphism did not influence overall survival (OS) or progression free survival (PFS) in our sample (OS; 37.6 vs 34.4 months (P=0.759), PFS; 49.6 vs 26.0 months (P=0.434)). These findings indicate that the BIM deletion polymorphism is common in Korean NSCLC patients but does not significantly affect the intrinsic biologic function of BH3-only protein. Furthermore, the BIM deletion polymorphism did not predict clinical outcomes in patients with NSCLC.
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Eun Na
EN
Cho
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Eun Young
EY
Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Ji Ye
JY
Jung
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Arum
A
Kim
Chonnam National University Hwasun Hospital, Republic of Korea.
In Jae
IJ
Oh
Chonnam National University Hwasun Hospital, Republic of Korea.
Young Chul
YC
Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: yschang@yuhs.ac.
Yoon Soo
YS
Chang
D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D000072224:Bcl-2-Like Protein 11; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D012907:Smoking / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors
BIM intron 2 deletion polymorphism; Non-small cell lung cancer; Prognosis; Risk factors; bcl-2-like 11