Sex differences in obesity related cancer incidence in relation to type 2 diabetes diagnosis (ZODIAC-49)

BACKGROUND Diabetes and obesity seem to be partly overlapping risk factors for the development of obesity-related cancer (mainly breast, prostate and colorectal cancer) in patients with type 2 diabetes (T2DM). In the general population, women have a lower risk for obesity-related cancer compared to men. Previous studies involving cardiovascular disease have shown that T2DM eliminates a female advantage of lower CVD risk in the general population compared to men. It is unclear whether the same could be true for obesity-related cancer. This study aimed to this investigate obesity-related cancer incidence in women and men known with T2DM as compared to the Dutch general population. METHODS This study included 69,583 patients with T2DM selected from a prospective primary care cohort, which was linked to the Dutch National Cancer Registry to obtain cancer specific data. Obesity-related cancers included liver, kidney, colorectal, gallbladder, pancreas, ovarian, endometrial, advanced prostate cancer, post-menopausal breast cancer and oesophageal adenocarcinoma. Primary outcome was sex-stratified, age and year of cancer diagnosis adjusted standardized incidence ratios (SIRs) for three time periods: 5 years before, the year after diagnosis and the next 4 years after T2DM diagnosis. The Dutch general population was used as reference group. RESULTS Women with T2DM were at an increased risk for obesity-related cancer compared to women in the general population already 5 years before diabetes diagnosis (SIR 1.77; 95%CI: 1.63-1.91). In both men and women, there was a peak in obesity-related cancer incidence following diabetes diagnosis (SIR: 1.38; 95%CI 1.11-1.64 and SIR: 2.21; 95%CI 1.94-2.30, respectively). From the second to the fifth year after diabetes diagnosis the obesity-related cancer incidence was higher in women compared to women in the general population (SIR: 2.12; 95%CI 1.94-2.30). CONCLUSIONS Women with T2DM seem to have a substantially higher obesity-related cancer risk. As opposed to men, in women this risk was already increased years before diabetes diagnosis. These results could imply that a relative advantage of women in the general population with regard to cancer risk is lost in women with T2DM.