Background:  

Tobacco smoking is a leading cause of lung cancer, but the magnitude of risk associated with low frequency smoking (average intensity <10 cigarettes per day) is not well quantified, particularly across combinations of smoking intensity and duration.  

Objectives:  

To quantify lung cancer risk associated with low frequency smoking in the pooled SYNERGY case–control data, evaluating intensity and duration jointly and assessing whether associations differed by sex. 

Methods:  

We restricted the analysis to never-smokers and ever-smokers with low frequency smoking, defined as an average smoking intensity of fewer than 10 cigarettes per day (CPD). The analytic dataset included 2,764 lung cancer cases (1,199 women; 1,565 men) and 10,305 controls (3,333 women; 6,972 men) from 14 studies in the SYNERGY project. We fitted unconditional logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for smoking intensity and smoking duration, specified as categorical and continuous variables and adjusted for age group, ever employment in a job with known lung cancer risk (List A) and study centre.  We conducted analyses stratified by sex.  

Results:  

For long term smokers ( ≥20 years), ORs in men were 3·42 (CI 2·55–4·54) for 1-3 CPD, 3·71 (CI  3·10–4·43) for 4-6 CPD, and 6·83 (CI  5·83–8·02) for 7-9 CPD; in women, the corresponding ORs were 0·83 (CI  0·45–1·44), 2·23 (CI  1·65–2·99), and 3·47 (CI  2·67–4·51). For shorter durations in the 4-6 CPD category, OR were 1·55 (CI  1·09–2·15) for duration up to 9 years and 1·57 (CI  1·09–2·22) for 10–19 years in men, and 0·78 (CI 0·39–1·44) and 0·55 (CI 0·27–1·02) in women. Using pack-years, ORs in men rose from 1·68 (CI 1·41–2·00) for >0–5 pack-years to 9·98 (CI 7·51–13·3) for >20 pack-years; in women, the corresponding ORs were 0·87 (CI 0·67–1·12) and 3·10 (CI 1·61–5·93). Among participants who smoked 7-9 CPD, the OR declined with increasing time since quitting in men, from 8·30 (CI 5·75–11·94) for quitting 2–7 years ago to  2·12 (CI 1·54–2·88) for ≥26 years; in women, corresponding ORs were lower and less monotonic: 3·10 (CI 1·63–5·92),and 1·43 (CI 0·54–3·45), respectively. 

Conclusion:  

Low frequency smoking (<10 CPD) was associated with substantial lung cancer risk, particularly with long duration, and risk remained elevated compared to never-smokers across low-intensity categories. The lower ORs with increasing time since quitting support cessation-focused public health strategies that explicitly address low frequency smoking rather than treating it as a low-risk pattern. The clear sex differences suggest that men may have additional risk factors that act jointly with smoking, even at low levels.