The transcription profile of CHRNA5 depleted MCF7 cells showed a significant positive correlation with that of A549 lung cancer cell line while exhibiting a negative association with the CHRNA5 co-expression profile obtained from Cancer Cell Line Encylopedia (CCLE).
These studies identify pharmacological tools from two distinct classes of drugs, antagonists and modifiers that are α5 and α5-D398N subtype selective that provide a means to characterize the role of the CHRNA5/A3/B4 gene cluster in smoking and cancer.
Our microarray results reveal that knockdown of the CHRNA5 gene encoding α5-nAChR significantly modulates key pathways including the cell cycle, DNA replication, pathway in cancer.
Our data suggest that gene variance in the CHRNA5-CHRNA3-CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco-related cancer in smokers.
However, no studies have investigated the association between CHRNA5rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer.
A case-control study of 866 ESCC patients and 952 healthy controls was performed to study the association of polymorphisms (rs667282 and rs3743073) in CHRNA5-A3-B4 with cancer risk using logistic regression models.
We examined the associations between the nicotinic acetylcholine receptor polymorphism (rs1051730) on chromosome 15q25 marking the gene cluster CHRNA3-CHRNB4-CHRNA5, smoking behavior, and tobacco-related cancer and lung and cardiovascular diseases in the general population.
Genome-wide association studies have provided evidence that common variation at 5p15.33 [telomerase reverse transcriptase (TERT)-cleft lip and palate transmembrane 1-like (CLPTM1L)], 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) influences lung cancer risk and cancer types with strong environmental risk factors.