Timothy Donahue

MD

UCLA

Chief, Division of Surgical Oncology

PLCO (Learn more about this study)

PLCO-850

Nov 3, 2021

Estrogen Exposure and Pancreatic Cancer Risk

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm and is notorious for its low 5-year survival rate (10.8%) and resistance to chemotherapy, making it one of the deadliest cancers worldwide. While some pancreatic neoplasms—solid pseudopapillary neoplasm and mucinous cystic neoplasm to name a few—have a predilection for XX individuals, PDAC has a higher incidence in XY individuals (4.9 per 100,000) compared to XX (3.6 per 100,000) individuals. Notably, this difference is attenuated by increasing age, with incidence of PDAC in post-menopausal XX individuals approaching that of XY individuals. The mechanisms underlying pancreatic tumorigenesis are poorly understood, but risk factors for the development of PDAC include smoking, obesity, diabetes, history of chronic pancreatitis and certain hereditary cancer syndromes. Given observed sex differences in PDAC incidence and mortality along with greater recognition of sex (distinct from gender) as a biological variable, increasing attention has been devoted to studying sex differences in pancreatic cancer. To date, most of the literature has focused on the role of sex steroid hormones and their receptors. However, a systematic review of estrogen receptor expression in pancreatic tumors revealed inconsistent and heterogenous approaches to receptor profiling that have provided few insights. Epidemiological studies attempting to draw associations between estrogen exposure and pancreatic cancer risk have led to conflicting results. We seek to better understand how estrogen exposure over an XX individual’s lifetime affects their risk of developing PDAC.

Specific Aim 1: To investigate the effect of estrogen exposure, both endogenous and exogenous, on pancreatic cancer risk using Cox proportional hazard modeling.

Specific Aim 2: Investigate whether the association between estrogen exposure and pancreatic cancer risk is modified by known pancreatic risk factors including body mass index, diabetes mellitus, tobacco use, alcohol use and history of chronic pancreatitis.

Hypothesis:
We hypothesize that increased estrogen exposure is associated with a decreased risk of developing PDAC.