Kara Michels, PhD, on Metabolic Syndrome and Ovarian Cancer Risk
Specific components of metabolic syndrome, including hypertension and high triglycerides, may modestly increase ovarian cancer risk, according to findings from a case-control study of linked US Surveillance, Epidemiology and End Results-Medicare data.1
The study included cases of ovarian or fallopian tube cancers (n = 16,850), which had been diagnosed between ages 68 and 89 years from 1994 to 2013, and controls, who were Medicare enrollees without these cancers living in registry areas.1 The effect of metabolic syndrome on ovarian and fallopian tube cancer risks was assessed as a composite and by individual components of metabolic syndrome, including obesity, impaired fasting glucose, hypertension, and triglycerides.1
Results of the study indicated that women with metabolic syndrome had lower risk of ovarian cancer compared with women without metabolic syndrome, when metabolic syndrome was assessed as a composite.1 However, the presence of 1 to 2 metabolic syndrome components was associated with increased risk of ovarian cancer compared with women with no components. The presence of 3 or more components was not associated with increased risk, the authors of the study noted.1
Hypertension and high triglycerides – the most prevalent components among women without metabolic syndrome – were found to be associated with increased ovarian cancer risks (ORs 1.08 and 1.05 respectively).1 However, impaired fasting glucose – a highly prevalent component among women with metabolic syndrome – was associated with reduced risk (OR 0.90).1
Endocrinology Consultant discussed these findings further with lead study author Kara Michels, PhD, from the National Cancer Institute Division of Cancer Epidemiology and Genetics.
Endocrinology Consultant: What prompted you to perform this study?
Dr Michels: Of all gynecologic cancers, ovarian cancer has the poorest survival rates.2 It is typically diagnosed at advanced stages because the symptoms of the disease are nonspecific. There are also very few risk factors for ovarian cancer that we can easily identify and potentially change.
We wanted to understand if metabolic syndrome–a measurable, frequently assessed, and potentially treatable condition–was associated with risk for developing ovarian cancer. We also investigated whether the clinical signs of metabolic syndrome, like hypertension and high triglycerides, individually increased risk for ovarian cancer and its subtypes.
Endo Con: Were these findings anticipated, or did any of them come as a surprise?
Dr Michels: We were able to confirm some findings from other research groups, but we also expanded upon them in critical ways. For example, we believe this is the first study to look at the components of metabolic syndrome and risk for ovarian cancer by tumor grade, so our identification of modestly increased risks for high-grade tumors with high triglycerides is unique. We also found a potential increased risk for ovarian cancer with hypertension, and this risk was greater for black women than for white women. Results from other studies also suggest a relationship between ovarian cancer risk and hypertension, but our observation among black women is novel and more research should be done to confirm it.
Our paper also discusses the problems that can arise when evaluating metabolic syndrome as a composite ovarian cancer risk factor. We observed that some of the metabolic syndrome components increased ovarian cancer risk and some decreased risk. This suggested to us that it is more useful to study the individual components when trying to identify risks for ovarian cancer, rather than combine them into a single measure. Each metabolic syndrome component could play a unique biologic role in the development of ovarian cancer.
Endo Con: What key take-home message do you hope clinicians learn from your study? At present, might these findings inform clinical practice in any way?
Dr Michels: Rather than immediately informing clinical practice, I think our study provides important and much-needed direction for research on the causes of ovarian cancer. Our findings are in line with those of other studies that indicate metabolic syndrome and its components are not strong ovarian cancer risk factors. However, specific components may play a role in the development of this disease. Our observations that high triglycerides and hypertension may increase risk merit additional research. Furthermore, the high prevalence of metabolic syndrome in the general population calls attention to the importance of improving and managing metabolic health among postmenopausal women.
Endo Con: Do you and your team currently have any hypothesis as to why hypertension and triglycerides appear to raise ovarian cancer risk, but not impaired fasting glucose?
Dr Michels: We need more studies on these topics, so trying to understand the scientific consensus on the specific roles that these metabolic syndrome components play in the development of ovarian cancer is difficult. For impaired fasting glucose and type 2 diabetes in particular, studies reach conflicting conclusions. This is, in part, because these clinical signs represent changes in not one, but multiple biologic pathways at a cellular level. Additionally, there are many different treatment options that women pursue when diagnosed with these clinical signs. For example, medications or changes in diet and physical activity may affect cancer risk, and they may change the way that hypertension, high triglycerides, or impaired fasting glucose affects cancer risk.
There are many interesting hypotheses from other researchers on why ovarian cancer develops and is such an aggressive disease, and our study shows we should continue to examine some of these ideas. Other studies support the observation that hypertension may modestly increase ovarian cancer risk, but they also suggest that the use of certain medications could be underlying this relationship. Another recent study found that ovarian cancers may be more likely to metastasize when the cancerous cells can uptake fatty acids, like triglycerides, from their environment.
Endo Con: What is the next step in terms of future research endeavors?
Dr Michels: In the near future, I think we will see more studies investigating whether specific treatments for metabolic syndrome components are associated with risk for ovarian cancer. I also hope we will continue to study how ovarian cancers may uniquely develop and metastasize in black women.
- Michels KA, McNeel TS, Trabert B. Metabolic syndrome and risk of ovarian and fallopian tube cancer in the United States: An analysis of linked SEER–Medicare data [Published online September 5, 2019]. Gynecol Oncol. https://doi.org/10.1016/j.ygyno.2019.08.032.
- Siegel RL, Miller KD, Jemal Al. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34. https://doi.org/10.3322/caac.21551.