SUMMARY: The American Cancer Society estimates that in 2022, about 62,210 people will be diagnosed with pancreatic cancer and 49,830 people will die of the disease. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States and Western Europe. Unfortunately, unlike other malignancies, very little progress has been made and outcome for patients with advanced pancreatic cancer has been dismal, with a 5-year survival rate for metastatic pancreatic cancer of approximately 10%. Pancreatic cancer has surpassed breast cancer as the third leading cause of cancer death in the United States and is on track to surpass colorectal cancer, to move to the second leading cause of cancer related deaths in the United States.
Majority of patients with pancreatic cancer (80% of cases) are diagnosed at an advanced stage, and are not amenable to curative surgical resection, at the time of diagnosis. The current treatment regimens for advanced disease have proved ineffective, conferring a median Overall Survival (OS) of 6-8 months. Clinical surveillance is recommended for individuals at high risk, although pancreatic cancer has relatively few established risk factors.
Polycystic Ovary Syndrome (PCOS) is a hormone disorder affecting 7-10% of women of childbearing age and is the most common cause of infertility. In the United States, an estimated 5-6 million women have PCOS and is the most common hormonal disorder among women of reproductive age. The etiology of PCOS is unknown and the signs and symptoms of PCOS have been attributed to abnormal levels of Luteinizing Hormone (LH) and androgen excess, which interfere with normal function of the ovaries. Hyperinsulinemia and insulin resistance can lead to the development of Type 2 diabetes and worsen androgen excess. A previously published study using Swedish register data suggested several carcinogenic processes associated with PCOS, with a 3.4-fold increased risk of pancreatic cancer, in small group of women with PCOS (JAMA Oncol. 2019;5(1):106-107).
To confirm these findings, the authors conducted a case-control study using data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. The study population included 446 women (N=446) who were 21 years of age or older and had pathologically or cytologically confirmed pancreatic adenocarcinoma. The control group consisted of visitors accompanying patients to Memorial Sloan Kettering Cancer Center clinics or spouses of patients with pancreatic cancer with no personal history of cancer (N=209). The researchers followed STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline to report their observational research findings and used multivariable logistic regression to estimate Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for the association between PCOS and risk of pancreatic cancer. The median age of the study population was 60 years.
The researchers noted a positive association between PCOS and risk of pancreatic cancer, after adjusting for age, race and ethnicity, BMI, and estrogen use (OR=1.88 – 88% more likely). The Odds Ratio remained significant at 1.78 after adjusting for potential mediator Type 2 diabetes, in addition to all the above factors. Excluding those with pancreatic cancer diagnosed less than 5 years after PCOS diagnosis, history of pancreatitis and a history of familial pancreatic cancer did not materially alter risk estimates. These findings suggested that this association of PCOS and risk of pancreatic cancer was independent of BMI, and not driven by Type 2 diabetes or other variables. The researchers hypothesized that these data suggest some individuals may have unknown metabolic derangements that may underly the development of both conditions.
The authors concluded that in this case-control study, PCOS was strongly associated with increased risk of pancreatic cancer. They added that diagnosis of PCOS may warrant increased education and clinical vigilance for pancreatic cancer, although prospective studies are needed to examine underlying biologic mechanisms and confirm this study findings.
Association Between Polycystic Ovary Syndrome and Risk of Pancreatic Cancer. Peeri NC, Landicino MV, Saldia CA, et al. JAMA Oncol. Published online October 6, 2022. doi:10.1001/jamaoncol.2022.4540
