Key gene af­fects abil­ity to quit smok­ing

Peo­ple who process nico­tine faster more likely to have dif­fi­culty kick­ing the habit

Toronto Star - - CLASSIFIED - DR. RACHEL TYNDALE Rachel Tyndale is a pro­fes­sor of psy­chi­a­try and phar­ma­col­ogy and tox­i­col­ogy at U of T, and serves as head of phar­ma­co­ge­net­ics at the Cen­tre for Ad­dic­tion and Men­tal Health. Doc­tors’ Notes is a weekly col­umn by mem­bers of the U of T Facu

Quit­ting smok­ing is far harder for some peo­ple than oth­ers — and it turns out that your own per­sonal ge­net­ics play a large role in de­ter­min­ing suc­cess, both in quit­ting cold turkey, but also in find­ing the best ther­a­pies to sup­port smok­ing ces­sa­tion.

In the fu­ture, a sim­ple ge­netic test will help you find the most ef­fec­tive treat­ment, but for now, it’s worth try­ing dif­fer­ent ap­proaches un­til you suc­ceed.

The more sci­en­tists know about the genes that make up our per­sonal blue­print, the more we can tai­lor pre­ven­tion strate­gies and treat­ments to in­di­vid­ual pa­tients.

This is most fa­mously true with diseases like can­cer. But as we learn more about our genes, we’re able to use the in­for­ma­tion for a wider va­ri­ety of health con­di­tions.

As a sci­en­tist study­ing ad­dic­tions, I’m very en­cour­aged by the amount we’re learn­ing about the ge­net­ics of to­bacco ad­dic­tion.

Just last year, we and oth­ers showed that ge­netic fac­tors in­flu- ence who can stop smok­ing cold turkey, and also which treat­ments will be most ef­fec­tive in help­ing you to quit.

A key gene, CYP2A6, helps de­ter­mine how quickly our bodies process nico­tine.

About 25 to 40 per cent of us are slow to get rid of the nico­tine from their sys­tems and so have an eas­ier time over­all: they smoke less and in­hale less deeply.

They’re most likely to be able to quit cold turkey and they also re­spond well to be­havioural coun­sel- ling and the nico­tine patch.

Peo­ple who process nico­tine faster strug­gle harder to give up smok­ing. Un­for­tu­nately, that’s the ma­jor­ity of us at 60 to 75 per cent. Re­cently, when re­searchers showed these “fast nico­tine pro­ces­sors” pho­tos of peo­ple smok­ing, to test Pavlo­vian re­sponses, and took pictures of their brains, they had more in­tense re­ac­tions than the slow pro­ces­sors did — sug­gest­ing that, as these smok­ers try to quit, they’ll face greater temp­ta­tion in their daily lives. This group also has a much harder time quit­ting cold turkey, but when they man­age to give it up, the ben­e­fits are huge.

For ex­am­ple when us­ing vareni­cline (Champix/Chantex) to help stop smok­ing, they show greater im­prove­ments in their anx­i­ety lev­els, ir­ri­tabil­ity and fo­cus. For fast pro­cessers, vareni­cline works bet­ter than the patch.

When we scanned the brains of smok­ers, my col­leagues and I found that the fast pro­cessers showed more ac­tiv­ity be­tween parts of the brain in­volved with ad­dic­tion; there were no dif­fer­ences in non-smok­ers — in­di­cat­ing you had to be both pre­dis­posed (a fast me­tab­o­lizer by ge­net­ics) and a smoker.

These brain changes help to un­der­score the im­por­tance of our ge­netic makeup in de­ter­min­ing how the brain adapts to ad­dic­tive drugs.

That’s why know­ing whether you’re a fast or a slow nico­tine pro­cesser will help you and your health provider to come up with the best treat­ment plan.

While still in rel­a­tively early stages, both a ge­netic test and a biomarker test should be com­mer­cially avail­able in the fu­ture to help guide treat­ment choices.

I also hope that the more we learn about ge­net­ics and smok­ing, the more this knowl­edge will re­move the frus­tra­tion and stigma that many smok­ers feel when they aren’t able to quit, even though other peo­ple are suc­cess­ful.

If you’ve been un­able to quit, it’s im­por­tant to re­al­ize you are not “weak” — the play­ing field is not level.

Sci­en­tists es­ti­mate that ge­net­ics ac­count for 60 to 70 per cent of our abil­ity to stop smok­ing.

There may well be ge­netic forces that make quit­ting much tougher for you — so be un­der­stand­ing with your­self and try dif­fer­ent meth­ods to quit as the con­se­quences of con­tin­ued smok­ing are also worse for fast pro­ces­sors.

In the mean­time, sci­en­tists will con­tinue to make new dis­cov­er­ies.

The more we un­der­stand about our own bodies’ re­ac­tion to ad­dic­tive drugs, the more suc­cess­ful we’ll be at tai­lor­ing pre­ven­tion and cur­rently avail­able treat­ments and cre­at­ing new treat­ments.

If you have been un­able to quit, it’s im­por­tant to re­al­ize you are not “weak” — the play­ing field is not level


Know­ing whether you’re a fast or slow nico­tine pro­cesser will help you and your health provider come up with the best treat­ment plan.

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