Association between -276 C/T polymorphism of the ERBB3 gene and lung cancer risk in a Korean population.
OBJECTIVE
The associations between the polymorphisms in the promoter region of the V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) gene and lung cancer risk were investigated.


METHODS
By direct sequencing, we first found two known polymorphisms (-536 A/G and -276 C/T). Further TaqMan assays and logistic regression analyses were performed in order to characterize the association between the -276 C/T polymorphism of ERBB3 and lung cancer risk in 425 patients with lung cancer and 411 healthy controls. To examine the potential effects of the -276 C/T polymorphism on ERBB3 transcription, luciferase reporter assays were performed in non-small cell lung cancer (NSCLC) cell lines.


RESULTS
The -276 C/T polymorphism was associated with the risk of lung cancer in a recessive model of never-smokers. Interestingly, the T allele conferred significantly lower promoter activity by 32% and 33% than the C allele in H2009 and H358 cell lines.


CONCLUSIONS
ERBB3 promoter polymorphisms affect ERBB3 gene expression, and contribute to genetic susceptibility to lung cancer in never-smokers.
Genomic Research Center for Lung and Breast/Ovarian Cancers, Korea University Anam Hospital, Seoul, Republic of Korea.
Jae Sook
JS
Sung
Lihua
L
Jin
Ukhyun
U
Jo
Kyong Hwa
KH
Park
Yeul Hong
YH
Kim
D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001483:Base Sequence; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D018815:Genes, erbB; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000009:adverse effects