Smoking is a major killer and is responsible for causing approximately one-third of all cancers and two third of lung cancers. In addition to cancers, smoking can cause cardiac, pulmonary, and vascular disorders like coronary artery diseases, emphysema, asthma, and chronic bronchitis, which could potentially be fatal. It is believed that the life span of an individual is reduced by 11 minutes for every cigarette he or she smokes. The average life span of chronic smokers is ten years lower than that of their non-smoking counterparts.

However, there are individuals who have long life spans despite being chronic smokers. In fact, some chronic smokers have crossed the age of 100 years. The genetic makeup of these individuals may hold a key for identifying variations in genes that can prevent cancer development in smokers.

The researchers at the University of Southern California, Davis School of Gerontology, led by Dr. Eileen Crimmins and Dr. Morgan Levine, studied the average life expectancy of smokers compared to nonsmokers of similar age. Their observations were the following:

• Young smokers had a lower life expectancy than their non-smoking counterparts.
• In older subjects, the life expectancy of smokers began approaching the life expectancy of non-smokers.
• Once the age group of subjects crossed 80 years, the life expectancy of smokers was the same as that of non-smokers.

The authors concluded that with advancing age among smokers, the process of smoking might have selected those individuals who had the variations in genes (alleles) necessary for providing immunity against smoking-induced cancer, in order for them to have survived till old age.

To identify the variation in genes (alleles) that could prevent development of cancer in smokers, the researchers used the fact that the genetic code is 99.9% similar in all human beings, and that it may occasionally differ  in single base regions, which are known as single nucleotide polymorphisms. These single nucleotide polymorphisms may be in the non-coding region of DNA or introns or the coding region of genes or exons. Following the research team sequenced the DNA of smokers and non-smokers who were in the age group 52-79 and greater than 80 years to identify nucleotide polymorphisms in the coding region of the genes.

The results showed that

• Smokers 80 years or older had distinct variations in 251 genes.
• These 251 genes’ variations in healthy smokers involved pathways associated with stress response (DNA repair), cell survival, aging, etc.

To sum up, the process of chronic smoking killed a majority of the smokers, but some individuals who had specific variations (single nucleotide polymorphisms) in certain (251) genes had a normal lifespan comparable to non-smokers. Whether the single nucleotide polymorphisms render any selective advantage for survival in the individuals tested would be an interesting investigation. Dr. Crimmins and her group intend to study more subjects and develop a robust assay to identify individuals susceptible to cancer upon smoking.

Written by Dr. Ashish Patil