Objective

Tomasetti and Vogelstein proposed that the variation in cancer risk among tissue is explained by the number of stem cell division. This was interpreted as “bad luck” due to random mutations arising during DNA replication non-cancerous stem cells. Smoking is considered the main aetiological risk factor for lung cancer. The aim of our study is to compare the proportions of the two main histological subtypes in smokers and never smokers in patients with lung cancer to determine the impact of smoking.

Methods

Data were retrospectively analysed from a prospectively collated database at our institution over a 7 year period. Data were compared for the two main historical subtypes of squamous and adenocarcinoma (subtyped according to the new IASLC adenocarcinoma classification). Frequencies were compared using Fishers exact or Chi square tests as appropriate to the data.

Results

A total of 2170 patients underwent surgery for lung cancer from March 2008 to November 2014. The mean age was 66 (12SD) years and 48% were female. The relative proportion of patients with squamous carcinoma was significantly different between smokers (27.0%) and never-smokers (5.7%)P <0.001 with a risk ratio of 4.70 (95% CI 2.9 to 7.6).The relative proportions between patients with adenocarcinoma were similar between smokers (48.3%) and never-smokers (54.4%) P=0.06 with a risk ratio of 0.89(0.79 to 1.00).

Conclusion

Smoking remains an important aetiological risk factor for the development of primary lung squamous cell carcinoma. For adenocarcinoma, the relative proportions between smokers and never-smokers were similar, supporting Tomasetti and Vogelstein hypothesis of random mutations arising during DNA replication in normal non-cancerous stem cells – or simply put as "bad luck".