Lung Cancer Risk Linked to Time-to-First Cigarette

Time-to-first cigarette may be a novel marker for lung cancer risk in smokers

medwireNews: Smokers who wait an hour or more from waking until their first cigarette of the day have a lower risk of developing cancer than their peers who light up earlier in the day, research suggests.

Neil Caporaso, from the National Cancer Institute in Bethesda, Maryland, USA, and colleagues believe this simple marker of nicotine dependency may improve on current markers of lung cancer risk stratification.

“TTFC [time-to-first cigarette] explains differences in lung cancer risk among smokers after accounting for smoking intensity, duration, and pack-years”, they write in the Journal of the National Cancer Institute.

“The ease of obtaining TTFC suggests opportunities for using measures of tobacco dependency in the clinic and in research.”

The team examined data for 3,249 Italian ever-smokers who participated in the Environment and Genetics in Lung Cancer Etiology study (EAGLE), including 1,812 patients who were diagnosed with primary lung cancer between 2002 and 2005, and 1,437 controls.

Compared with individuals who waited at least 60 minutes from waking before smoking their first cigarette, participants who smoked within 31 to 60 minutes, 6 to 30 minutes and 5 or fewer minutes were a significant 2.57, 2.27 and 3.50 times more likely to be diagnosed with lung cancer, after adjusting for smoking intensity, duration, pack–years, time since quitting and other modifiers.

Moreover, the incidence of lung cancer was significantly higher in participants who smoked in the first 60 minutes of wakening than those who waited at least an hour, regardless of whether they smoked up to 10 cigarettes a day (64.1 vs 11.7 per 100,000 person–years), 11 to 20 cigarettes (125.6 vs 28.6), 21 to 30 cigarettes (130.1 vs 40.7) or more than 30 cigarettes per day (260.8 vs 108.9).

Similarly, there was a significantly greater incidence of lung cancer for patients with high nicotine dependency, defined as TTFC of 60 minutes or less, compared with patients with a lower dependency, when examined by smoking duration or pack–years.

Data for 6,725 participants of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening trial in the USA, in which 181 patients were diagnosed with lung cancer, were also examined by Neil Caporaso and co-authors.

Analysis revealed an overall borderline, but statistically significant, correlation between shorter TTFC and lung cancer risk, although significance was only reached for individuals with a TTFC of no more than 5 minutes, compared with a TTFC of 60 minutes or longer.

The team postulates that the weaker effect of TTFC in the PLCO than EAGLE data may be caused by chance heterogeneity related to the smaller number of lung cancer cases in PLCO, or differences in geographical location, gender and age of the populations.

The researchers therefore conclude: “[F]uture results from prospective and screening studies are needed to determine whether TTFC will improve risk prediction models and aid in the identification of high-risk subjects.

“Such work should be performed in diverse populations with distinct geographic origins and ethnicities.”


Gu F, Wacholder S, Kovalchik S, et al. Time to smoke first morning cigarette and lung cancer in a case–control study. JNCI 2014; Advance online 19 June. doi: 10.1093/jnci/dju209

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