Smoking and risk of epithelial ovarian cancer subtypes in three prospective cohort studies

Idlir LICAJ, The UiT Arctic University of Norway, Norway
JACOBSEN B. 1 , SELMER R. 2 , MASKARINEC G. 3 , WEIDERPASS E. 1,4,5,6 , GRAM I. 1

1 Department of Community Medicine, Faculty of Health Sciences, The UiT Arctic University of Norway, Tromsø, Norway;
2 Norwegian Institute of Public Health, Oslo, Norway
3 University of Hawaii Cancer Center, Honolulu, HI
4 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
5 Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
6 Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.

Purpose
Based on three cohorts, the main purpose of this prospective study was to examine the impact of smoking on the risk of epithelial ovarian cancer according to histological subtypes and invasiveness.
Methods
We followed 300,398 Norwegian women, born between 1899 and 1975, recruited from 1974-2003, by linkage to national virtually complete registries through December 2013. The three cohorts included the Norwegian Counties Study (1974–1988), the 40-Years Study (1985–1999), and the Cohort of Norway Study (1994–2003). We used multivariable Cox proportional hazard models, stratified by birth cohort and study cohort to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between smoking characteristics and epithelial ovarian cancer (EOC) histological subtypes.
Results
During >5.9 million person-years, with a median follow-up of 19 years, 2,336 primary epithelial ovarian cancers were identified, of which 1,647 (71%) were invasive and 689 (29%) borderline. In our study, 38% of women were current, 21% former and 41% never smokers. Current smokers had an increased risk of EOC of 11% (HR=1.11 95% CI, 1.01-1.22) compared to never smokers. When stratifying according invasiveness, the risk of invasive-EOC (HR=0.97 95% CI, 0.86-1.08) in current smokers was significantly different from the corresponding risk of borderline-EOC (HR=1.55 95% CI, 1.29-1.85) (pheterogeneity<0.0001). Compared with never smokers, current smokers had more than doubled risk of mucinous epithelial ovarian cancer (HR=2.09 95% CI, 1.67-2.62). When stratified according invasiveness, the corresponding figure was 78% increased risk of 78% [HR=1.78 95% CI, 1.20-2.64] for invasive-mucinous epithelial ovarian cancer and more than 100% increased risk [HR=2.26 95% CI, 1.71-2.97] for borderline-mucinous epithelial ovarian cancer (pheterogeneity=0.34).  
Conclusions
Independently of invasiveness status, smoking increases the risk of mucinous epithelial ovarian cancer.
 
Funding source
This research is supported by grants from the Norwegian Cancer Society.