To Smoke Or Not To Smoke!

close up photography of a person holding cigarette

To smoke or not to smoke? Perhaps, this is a question that hovers in every teenager’s mind!..and I and you are no exceptions…isn’t it? The unfathomable curiosity that drives a human mind towards the “First Puff” is generally attributed to the chemical drama of our hormones. Thereon, I am pretty sure we all have had this experience to observe many of our close friends who turned to be chain smokers and some just turned away from the nicotine drive. Even in my family I have observed that two siblings have diamterically opposite behavioural preferences when it comes to smoking or, broadly speaking, dependancy on tobacco.

All these observations always intrigued my inquisitiveness . The prominent question that dominated my mind:

Is There A Genetic Basis Behind All These?

Well, the answer is Yes! Long back scientists went ahead to investigate the role of a hereditary component to tobacco use. It is amazing to know that genetics has more than 50% contribution in various aspects of smoking like initiation, intensity i.e., amount smoked, persistence or years of smoking, acquiring dependency, inability to quit, etc.

How Does Genetics Work In The Background?

To explore this let us take the example of nicotine metabolism and observe how genetic variation in the genes of the enzymes involved reflect upon the smoking behaviour and the tobacco dependancy of an individual.

Genetic Variation And Genetic Polymorphism

Genetic variation is caused by minute differences among the DNA of individuals. This phenomenon gives rise to different forms of the same gene — called alleles. These alleles exist in different combinations inside the human genome. These allelic combinations vary from person to person in a population. This varied arrangements of alleles is popularly known as genetic polymorphism.

Presence or absence of certain genetic polymorphism(s) determines the development of unique features of individual preferences of smoking behaviour, dependancy, non-dependancy, ability to quit, etc.

Nicotine is a nitrogen containing chemical present in tobacco. It is heavily addictive and exposes people to the extremely harmful effects of tobacco dependency. In the human body, nicotine metabolism involves multiple step enzymatic pathways e.g., CYP2A6 and CYP2B6.

Studies suggest an important genetic contribution to total clearance of nicotine (nicotine → cotinine → 3-hydroxycotinine). Approximately, 10% of absorbed nicotine is excreted to urine unchanged. Up to 80% of nicotine is converted to cotinine.

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Inter-individual rates of nicotine metabolism vary substantially. CYP2A6 gene codes the main metabolic enzyme for nicotine (80% of hepatic nicotine oxidation).

To date, over 60 distinct CYP2A6 alleles have been identified

Individuals who carry reduced activity CYP2A6 alleles are more probably non-smokers, smoke fewer cigarettes per day, are less likely to progress to nicotine dependence, are less dependent on nicotine, may have an easier time quitting smoking, and have a lower risk of lung cancer. How interesting is that!

Undoubtedly, this type of knowledge of the underlying biological processes involved in the addiction of various smokers will lead to the identification of different types of smokers. Patient-specific therapy and therefore more effective and efficient treatment for tobacco dependence will soon follow.

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