EGFR Intron 1 polymorphism in Asian Populations and its correlation with EGFR gene expression and amplification in breast tumor tissues.
OBJECTIVE
The purpose of this study was to test the hypothesis if longer CA dinucleotide repeats are more common in the Asian population and also to gain insights into the interplay between the CA dinucleotide repeats and the frequencies of EGFR gene expression and amplifications as this might have therapeutic implications with regards to treatment with tyrosine kinase inhibitors.


METHODS
The EGFR intron 1 polymorphism was analysed in three distinct healthy Asian subjects, namely, Chinese (N = 96), Malays (N = 98) and Indians (N = 100). Comparative genomic hybridisation was performed to investigate for changes in DNA copy number in relation to the polymorphic CA dinucleotide repeats in breast tumor tissues (N = 22).


RESULTS
The frequency of short alleles with 14 and 15 CA repeats were most common in the Asian populations and significantly higher than those reported for Caucasians. The frequency of 20 CA repeats was 5%, almost 13-fold lower than previous reports. EGFR amplifications were detected in 23% and 11% of breast tumor tissues harboring short and long CA repeats, respectively.


CONCLUSIONS
Our results show that the frequency of alleles encoding for short CA dinucleotide repeats is common in Asian populations. EGFR expression and amplification levels were also higher in Asian breast tumor tissues with short CA dinucleotide repeats. These findings suggest that the EGFR intron 1 polymorphism may influence response to treatment with tyrosine kinase inhibitors in breast cancer patients and further studies are warranted.
Zhou
Qingyu
Q
Laboratory of Clinical Pharmacology, National Cancer Centre, Singapore.
Cheung
Yin Bun
YB
Jada
Srinivasa Rao
SR
Lim
Wan Teck
WT
Kuo
Wen-Lin
WL
Gray
Joe W
JW
Lee
Ann S G
AS
Chowbay
Balram
B
D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002681:China; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D007438:Introns; D008296:Malaysia; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D017931:DNA Primers; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases