Risk factors for second cancers
Friday 10 June - 10:00-10:30
photo intervenant Flora VAN LEEUWEN
Head of the Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, The Netherlands

Flora E. van Leeuwen graduated from the Wageningen Agricultural University (MSc in human Nutrition) in 1981 (cum laude). In the same year she became head of the Department of Tumor Documentation, Clinical Trials and Epidemiology of the Netherlands Cancer Institute in Amsterdam, with the specific task to start an Epidemiology group in that institute. In 1982-1983 she was awarded a research training fellowship by the International Agency for Research on Cancer and obtained a MSc degree in Epidemiology from the Department of Epidemiology of the School of Public Health of the University of Alabama in Birmingham, USA. From 1986-2010 she was Head of the epidemiology group of the Netherlands Cancer Institute. From 2010 onwards, she has been heading the Division of Psychosocial Research and Epidemiology in the Netherlands Cancer Institute. Her research group currently focuses on two main research lines: the assessment of the long-term risks of second malignancy, cardiovascular disease and other comorbidities following treatment for hodgkin's lymphoma, breast cancer, testicular cancer and childhood malignancy; the development and evaluation of cancer survivorship care programs and the assessment of the roles of hormone-related and genetic risk factors in the etiology of breast and ovarian cancers; special interest is in late effects of ovarian stimulation for in vitro fertilization and cancer etiology in BRCA1/2 families. In 1998 Flora van Leeuwen obtained a Chair in Cancer Epidemiology at The Faculty of Medicine from the Vrije Universiteit in Amsterdam.

Risk factors for second cancers

Currently, 17-19% of all new primary malignancies occur in individuals who have already survived a primary malignancy. In the Netherlands, the proportion of second and subsequent malignancies (including second cancers in paired organs) increased from 10% in 1989 to 17% in 2013. Most of this increase can be attributed to improved cancer survival. The occurrence of two primary malignancies in the same individual may result from host susceptibility factors (genetic predisposition, immunodeficiency),  lifestyle or environmental risk factors in common, treatment for the first malignancy, or interaction between these factors. Alternatively, two primary malignancies in a single individual may be unrelated and arise by chance alone. SMNs occurring at early ages are more likely to be caused by genetic factors or treatment of the first malignancy, while SMNs occurring at older ages are more likely to be related to lifestyle, or to arise through the play of chance.
Research conducted over the last three decades has clearly demonstrated that, paradoxically, several treatments used successfully to treat cancer have the potential to induce new primary malignancies: increased SMN risks have been observed after radiotherapy, certain chemotherapy regimens and hormonal treatments. Radiotherapy is associated with moderately increased risks of solid malignancies in the organs or tissues irradiated. The relative risk of solid tumors increases steadily with increasing follow-up time from 5-15 years since radiotherapy and remains elevated for at least 40 years. The relative risk of solid SMNs increases strongly with younger age at first treatment; this effect is most notable for breast cancer. The risks of lung, breast and gastrointestinal cancers increase with higher radiation dose, while the risks of leukemia and thyroid cancer decrease at high doses. According to recent estimates, radiotherapy accounts for 8% of all subsequent malignancies. This proportion, however, is much larger (30-70%) for SMNs occurring after primary malignancies (which used to be) treated with intensive radiation and chemotherapy regimens, such as childhood cancer and Hodgkin lymphoma.  
Recent studies show that alkylating agent chemotherapy does not only increase risk of acute myeloid leukemia, but can also increase the risk of solid malignancies, in particular cancers of the lung and gastrointestinal tract. Smoking appears to multiply the radiation- and chemotherapy-associated risks of lung cancer. Therefore, all cancer patients should be strongly advised to stop smoking.