Smoking Cancer Project

About the project

This project is primarily conducted by the Laboratory of Lifestyle Epidemiology (Department of Environmental Health Sciences), of the Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

The aim of this project is to provide a comprehensive and updated picture of the association between various smoking-related variables and site-specific cancer risk. We are able to estimate the most robust cancer-specific relative risks obtained from the existing scientific literature. Moreover, for each cancer site, we are able to provide the risk curves which best describe the dose-response effect of smoking intensity, smoking duration, pack-years, and time since stopping smoking on cancer risk.



This project includes a series of systematic reviews and meta-analyses based on three subsequent literature searches:
1) an umbrella review, to identify published meta-analyses, pooled-analyses, and systematic reviews on the association between cigarette smoking and cancer risk;
2) for each cancer site, an updated systematic review of original publications on the association between cigarette smoking and site-specific cancer risk, starting from the last available comprehensive review identified through the umbrella review;
3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review or through the update of the reviews.

The primary outcomes of interest are: i) the excess incidence/mortality of various cancers for smokers compared to never smokers; ii) the dose-response curves describing the association between smoking intensity, duration, and time since stopping and incidence/mortality for various cancers. For each cancer site, we perform a meta-analysis by pooling the study-specific estimates for smoking status. We also estimate the dose-response curves for other smoking variables through random-effects meta-regression models based on a nonlinear dose-response relationship framework.


List of cancer sites

Pancreas (already available)

Kidney (already available)

Ovary (already available)

Gallbladder (already available)

Colorectum (article under review)

Stomach (article in preparation)

Breast (in process)

Liver (in process)




Italian Association for Cancer Research (AIRC)

Italian Foundation for Cancer Research (FIRC)

Italian League Against Cancer (LILT, Milan)



Lugo A, Bosetti C, Peveri G, Rota M, Bagnardi V, Gallus S. Dose-response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews. BMJ Open. 2017 Nov 1;7(10):e018930. doi: 10.1136/bmjopen-2017-018930. PubMed PMID: 29092902

Lugo A, Peveri G, Bosetti C, Bagnardi V, Crippa A, Orsini N, Rota M, Gallus S. Strong excess risk of pancreatic cancer for low frequency and duration of cigarette smoking: A comprehensive review and meta-analysis. Eur J Cancer. 2018 Oct 19;104:117-126. doi: 10.1016/j.ejca.2018.09.007. PubMed PMID: 30347287

Liu X, Peveri G, Bosetti C, Bagnardi V, Specchia C, Gallus S, Lugo A. Dose-response relationships between cigarette smoking and kidney cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2019 Oct;142:86-93. doi: 10.1016/j.critrevonc.2019.07.019. PubMed PMID: 31387065

Santucci C, Bosetti C, Peveri G, Liu X, Bagnardi V, Specchia C, Gallus S, Lugo A. Dose-risk relationships between cigarette smoking and ovarian cancer histotypes: a comprehensive meta-analysis. Cancer Causes Control. 2019 Sep;30(9):1023-1032. doi: 10.1007/s10552-019-01198-8. PubMed PMID: 31236793

Lugo A, Peveri G, Gallus S. Should we consider gallbladder cancer a new smoking-related cancer? A comprehensive meta-analysis focused on dose-response relationships. Int J Cancer. 2019 Sep 12. doi: 10.1002/ijc.32681. [Epub ahead of print] PubMed PMID: 31513278