Understanding mechanisms of increased ovarian cancer risk due to young age at menarche and a high number of lifetime ovulatory cycles

Columbia University

Lay summary

Our research aims to explain why certain reproductive characteristics have been repeatedly found to be associated with ovarian cancer. Specifically, we will investigate the role of having a young age at menarche and a high number of lifetime ovulatory cycles on increasing ovarian cancer risk. Ovarian is the fifth most common cancer in women, and the most lethal gynecologic cancer, with approximately half of patients surviving for 5 years or more. There have been no substantial improvements in detection or treatment in the past 50 years, and current prevention recommendations for this deadly cancer are dismal; the only guidance is for premenopausal women at high genetic risk to have both ovaries removed, a serious and life-altering surgery for a woman in early adulthood.

Many researchers who study cancer and other chronic diseases postulate that most disease comes from an accumulation of interactions between genes, environment, and lifestyle over an individual's lifetime. Ovarian cancer is likely no exception to this hypothesis, especially in light of the role that characteristics like age at first period, number of pregnancies, use of oral contraceptives, and age at menopause seem to have in altering risk.

We propose that in-depth investigation of total lifetime ovulatory cycles, the best known correlate of ovarian cancer to date, is a promising way to uncover a deeper understanding of how the disease is caused. We aim to do this by asking two specific questions: does having a young age at menarche increase ovarian cancer risk outside of its impact on increasing the number of lifetime ovulatory cycles, and, do genes that have been found to increase the risk of ovarian cancer work together with a high number of lifetime ovulations to further increase the chance of getting this cancer? Together, this information could lead us to the identification of modifiable risk factors that can be used to inform prevention.

The extensive UK Biobank provides an excellent opportunity to explore these questions. Participants were asked all of the questions needed for the calculation of LOC, and were also run on a laboratory assay that produced genetic data for over 250,000 women, including 1055 ovarian cancer cases. Over the course of up to 2 years that will be spent analyzing these data, presenting findings to colleagues, and preparing manuscripts for publication, the proposed study has the potential to produce novel information that ultimately will increase the health of women.