Novel Mutations of the CHRNA3 Gene in Non-Small Cell Lung Cancer in an Iranian Population

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Lung cancer, the leading cause of cancer-related worldwide deaths, largely results from the combined </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">effects of smoking exposure and genetic susceptibility. CHRNA3, a nicotinic acetylcholine receptor gene, is associated with lung cancer risk. This study sought to identify variations in exon 3 of CHRNA3 in an Iranian population with </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">non-small cell lung cancer (NSCLC). </span></span><strong><span style="font-size: small;">Materials and methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">A case-control study including 147 individuals with lung cancer and 145 healthy individuals was conducted. As mobility shift caused by nucleotide substitutions might be due to a conformational change of single-stranded DNAs, we designated these as single-strand conformation polymorphisms </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">(SSCPs). PCR amplified products with SSCP were subjected to DNA sequencing. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">The sequencing results </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">showed 3 polymorphisms in exon 3 of CHRNA3, rs8040868, rs763384023 and rs2869547 , the latter two of which </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">have not been reported in NSCLC, previously. </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">It appears that the rs8040868 may be considered as a </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">pathogenic mutation associated with the clinical phenotype. Polymorphisms are important factors for development of cancers and may provide additional insights into mechanisms underlying NSCLC. </span></span>