Dose-response Relationships Between Cigarette Smoking and Kidney Cancer: A Systematic Review and Meta-analysis - Beyond the Abstract

In our study, besides providing the most complete and updated quantification of the association between cigarette smoking and kidney cancer risk, for the first time we provided the dose-risk functions for smoking intensity, duration, and time since quitting.

Using an innovative approach for the identification of original publications, we conducted the present systematic review. Dose-risk relationships were evaluated using one-stage, random-effects restricted cubic splines or log-linear models.

Fifty-six original studies were included in our meta-analysis, providing pooled relative risks of kidney cancer of 1.39 for current and 1.20 for former compared with never smokers. Current smokers nonlinearly increased their risk of kidney cancer with increasing smoking intensity. The risk grew sharply even at relatively low smoking intensities. In fact, smoking only 5 cigarettes/day significantly increased the risk by 18%. The risk, although to a lower extent, continued increasing. The risk of kidney cancer demonstrated a significant linear increase with the duration of smoking: 24% higher for 10 years of smoking and 70% for 25 years of smoking. Kidney cancer risk decreased slowly with time since quitting cigarette smoking, with RRs for former vs. current smokers being 0.94 for 10 years of quitting, 0.88 for 20 years of quitting, and 0.82 for 30 years of quitting.

The systematic review was conducted using an original approach, combining an umbrella review and a traditional systematic review.1 This innovative approach guarantees the most comprehensive review in a relatively short period of time. What we experienced is that previously published systematic reviews are optimal sources of original articles. We are able to demonstrate that pooling the information obtained by previously conducted systematic reviews results in wider coverage of original articles than that using a traditional systematic review, even if well-conducted. This is particularly true when the topic has been abundantly investigated, as the association between tobacco smoking and the risk of common cancer like kidney cancer. For example, the last meta-analysis on the issue prior to ours was conducted by an excellent team, based on an appropriate traditional search strategy.2 This systematic review was able to identify 31 eligible articles published until 2013. Our methodological approach identified other 16 publications published before 2013, that could have been considered as eligible articles by Cumberbatch and colleagues.

In conclusion, the present comprehensive review and meta-analysis confirm that smoking increases the risk of kidney cancer by around 40%, the risk continuously increasing with smoking intensity and duration. Among former smokers, the risk of kidney cancer is 20% higher. Our dose-response curves suggest that heavy smokers cutting their intensity by half will only slightly reduce the risk of kidney cancer. Therefore, for effective kidney cancer prevention, it is essential that smokers quit smoking completely, and as soon as possible. The main findings of our meta-analysis are also published on a dedicated website (, where additional data could be provided by readers to keep the meta-analyses updated.

Written by: Xiaoqiu Liu, PhD, Alessandra Lugo, PhD, Silvano Gallus, ScD, Laboratory of Lifestyle Epidemiology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. 


1. Lugo A, Bosetti C, Peveri G, et al. 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;7:e018930. doi: 10.1136/bmjopen-2017-018930.

2. Cumberbatch et al., The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. 2016, Eur Urol. 2016 Sep;70(3):458-66. doi: 10.1016/j.eururo.2015.06.042. Epub 2015 Jul 3. 

Read the Abstract