Genetic Variant Reduces Likelihood of Quitting Smoking, Boosts Earlier Onset of Lung Cancer

People with risk factors on the CHRNA5 gene are more likely to develop lung cancer at a younger age, and new research suggests that the reason is they are less likely to quit smoking early in life. So rather than directly affecting the susceptibility to lung cancer, researchers found this gene appears to operate through dependence on smoking. The findings are published in the Journal of the National Cancer Institute by a research team including UW-CTRI Director of Research Dr. Tim Baker and led by Dr. Li-Shiun Chen of the University of Washington in St. Louis.

Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15, smoking quantity, and lung cancer. Chen, Baker, and Dr. Laura Beirut conducted a new meta-analysis to examine associations between a CHRNA5 genetic risk factor and age of quitting smoking, and age of lung cancer diagnosis in 24 studies of 29,000 people of European ancestry.

They found that persons with this risk factor at a critical location on the CHRNA5 gene (risk alleles at the rs16969968 single nucleotide polymorphism) had a lower likelihood of smoking cessation by age 50 and also showed a four-year delay in median age of quitting, compared to those without the risk factor. Among smokers with lung cancer diagnoses, those possessing the same risk factor had a four-year earlier median age of diagnosis compared with those with the low-risk genotype.

These data support the clinical significance of the CHRNA5 risk variant by showing that it predicts both delayed smoking cessation and an earlier age of lung-cancer diagnosis. Other research shows that this CHRNA5 risk factor predicts especially heavy smoking. It may be that it confers lung cancer risk by causing both heavier and more persistent smoking. Also, given the existing evidence that this CHRNA5 variant predicts especially favorable response to nicotine replacement pharmacotherapy, these findings underscore the importance of ensuring that those possessing this risk factor are provided such treatment.