The discordant twin pair study design is powerful to control for familial confounding. We employed this approach to investigate the associations of smoking with several cancers. The NorTwinCan study combines data from the Danish, Finnish, Norwegian and Swedish twin and cancer registries. Follow-up started when smoking status was determined and ended at cancer diagnosis confirmed by information in the cancer registry, death or end of follow-up. We classified the participants as never (n = 59 093), former (n = 21 168) or current (n = 47 314) smokers. We pooled data from twin pairs where one co-twin was diagnosed with any of the following tobacco-related cancers: esophagus, kidney, larynx, liver, oral cavity, pancreas, pharynx or urinary bladder, while their co-twin had none of those. Lung cancer was included in further analysis. We used Cox regression allowing for pair-specific baseline functions to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). For tobacco-related cancer sites, we recorded 7379 cases during median 27 years of follow-up. The analyses based on individual twins showed that former (HR 1.31, 95% CI: 1.17-1.48) and current (HR 2.14 [1.95-2.34]) smokers are at increased risk to develop one of cancers listed above, compared to never smokers. Among 109 monozygotic twin pairs discordant for cancer and smoking, the HR was 1.85 (95% CI: 1.15-2.98) among current smokers and 1.69 (1.00-2.87) among former smokers when compared to their never smoking co-twin. Thus, associations of smoking with several cancers were replicated for discordant identical twin pairs. Analyses based on genetically informative data provide evidence consistent with smoking causing multiple cancers.
Bibliografisk noteFunding Information:
Academy of Geriatric Cancer Research, Odense University Hospital AgeCare program; Juselius Foundation; Nordic Cancer Union; Nordic Union of Cancer; Terveyden Tutkimuksen Toimikunta, Grant/Award Numbers: 129680, 213506, 263278, 265240, 312073; The Ministry for Higher Education, Grant/Award Number: Swedish Twin Registry Funding information
This work was supported by funding from the Nordic Union of Cancer (PI J. Kaprio). The Finnish Twin Cohort was supported by the Academy of Finland (grant numbers 213506, 129680, 265240, 263278 & 312073) and the Sigrid Juselius Foundation (to J Kaprio). The Ministry for Higher Education financially supports the Swedish Twin Registry. The Danish Twin Cohort was supported by the Odense University Hospital AgeCare program of the Academy of Geriatric Cancer Research. Jennifer R Harris and Jacob Hjelmborg have received funding (2017‐2019) by grants from the Nordic Cancer Union, project entitled “Genetic Epidemiology and Familial Risk of Cross‐Cancer Associations: A Nordic Twin Study.” We acknowledge the contribution of all the researchers and staff of the twin and cancer registries contributing to the NorTwinCan project. We thank Alyce Whipp from University of Helsinki Language Services for language editing.