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. 2022 Jun;126(11):1637-1646.
doi: 10.1038/s41416-022-01736-3. Epub 2022 Feb 22.

Association of smoking and polygenic risk with the incidence of lung cancer: a prospective cohort study

Peidong Zhang #  1   2 , Pei-Liang Chen #  1 , Zhi-Hao Li  1 , Ao Zhang  3 , Xi-Ru Zhang  1 , Yu-Jie Zhang  1 , Dan Liu  1 , Chen Mao  4   5
Affiliations

Association of smoking and polygenic risk with the incidence of lung cancer: a prospective cohort study

Peidong Zhang et al. Br J Cancer. 2022 Jun.

Abstract

Background: Genetic variation increases the risk of lung cancer, but the extent to which smoking amplifies this effect remains unknown. Therefore, we aimed to investigate the risk of lung cancer in people with different genetic risks and smoking habits.

Methods: This prospective cohort study included 345,794 European ancestry participants from the UK Biobank and followed up for 7.2 [6.5-7.8] years.

Results: Overall, 26.2% of the participants were former smokers, and 9.8% were current smokers. During follow-up, 1687 (0.49%) participants developed lung cancer. High genetic risk and smoking were independently associated with an increased risk of incident lung cancer. Compared with never-smokers, HR per standard deviation of the PRS increase was 1.16 (95% CI, 1.11-1.22), and HR of heavy smokers (≥40 pack-years) was 17.89 (95% CI, 15.31-20.91). There were no significant interactions between the PRS and the smoking status or pack-years. Population-attributable fraction analysis showed that smoking cessation might prevent 76.4% of new lung cancers.

Conclusions: Both high genetic risk and smoking were independently associated with higher lung cancer risk, but the increased risk of smoking was much more significant than heredity. The combination of traditional risk factors and additional PRS provides realistic application prospects for precise prevention.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flow chart of participant enrolment.
BMI body mass index, TDI Townsend deprivation index.
Fig. 2
Fig. 2. Cumulative risk of incident lung cancer according to genetic risk or smoking.
Cumulative risk of incident lung cancer during follow-up according to genetic risk (a), smoking status (b) and smoking pack-years (c).
Fig. 3
Fig. 3. Risk of incident lung cancer according to a combination of genetic risk and smoking.
Risk of incident lung cancer according to genetic risk and smoking status (a) or genetic risk and smoking pack-years (b). The vertical line indicates the reference value of 1.
See this image and copyright information in PMC

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