Risk factors for breast and ovarian cancer
In the period 1995-2000, we established a nationwide cohort (OMEGA) of women treated with IVF between 1983 and 2000 (N=31,000) and a subfertile comparison group (N=10,300). Complete and detailed data are available on all IVF treatments and other fertility treatments, and lifestyle and reproductive factors. The cohort is periodically linked to the Cancer Registry. Our large study has the longest follow-up (median 21 yrs) and is the only one with a subfertile comparison group not treated with IVF. We recently showed that, reassuringly, ovarian stimulation for IVF does not increase the risks of breast and ovarian cancer, also not after more than 20 years (Van den Belt-Dusebout et al, JAMA 2016, Spaan et al, JNCI 2020). However, risk of borderline tumors of the ovary is ~2-fold increased. Furthermore, we observed that ovarian stimulation is associated with increased risk of colorectal cancer (Spaan et al, Clin Gastroenterol Hepatol 2016).
We also assessed cancer risk in a cohort comprising all children of OMEGA participants (n=~47,000) (Spaan et al, Hum Reprod 2019). After a median follow-up of 21 years, the overall risk for cancer in ART-conceived children was not increased.
We established and coordinate (together with Dr Matti A. Rookus, Senior Investigator) a nationwide cohort study on Hereditary Breast and Ovarian cancer in the Netherlands, aiming to assess the risks of various cancers and the modifying effects of reproductive and lifestyle factors as well as common genetic alterations on cancer risks in families tested for BRCA1/2 mutations (HEBON study; ~44,000 relatives, including ~8000 BRCA1/2 mutation carriers). We also coordinate the database and analyses of the International BRCA Carrier Cohort Study (IBCCS) and the epidemiological part of the cross-sectional study of the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
A Dutch-led IBCCS study showed that diagnostic radiation increases the risk of breast cancer in BRCA1 mutation carriers in a dose-dependent fashion (Pijpe et al, BMJ 2012). Other recent Dutch-led studies showed that oral contraceptives do not appear to be associated with long-term increased risk of breast cancer in BRCA mutation carriers. With the consortium we recently reported the first prospective risks of breast and ovarian cancer in BRCA carriers (Kuchenbaecker, JAMA 2017).