Chunliang Liu

M.D., Ph.D.

Second Hospital of Shanxi Medical University

Associate Professor

PLCO (Learn more about this study)

PLCO-1009

Aug 2, 2022

Dietary Intake of Phytoestrogens and Risk of Pancreatic Cancer in the PLCO Trial

Pancreatic cancer is the third leading cause of cancer-related deaths among both sexes in the United States (1). It is the deadliest of all common cancers with a five-year relative survival rate of only 11.5% (https://seer.cancer.gov/statfacts/html/pancreas.html), which is in part due to a lack of reliable screening tests for early diagnosis and effective treatment regimens for patients. Furthermore, the etiology of pancreatic cancer remains virtually elusive, although cigarette smoking, diabetes, chronic pancreatitis, and family history have been established as risk factors (2). To reduce the incidence and mortality of this intractable cancer, it is of paramount importance to identify more modifiable risk factors (e.g., diet) in epidemiological studies, especially prospective cohort studies.

Phytoestrogens are estrogen-like compounds derived from plants and have a similar structure to 17β-estradiol. Phytoestrogens are structurally divided into three major categories: isoflavones (e.g., genistein, daidzein, glycitein, formononetin, and biochanin A), coumestans (e.g., coumestrol), and lignans (3). Genistein, daidzein, and glycitein abound in soyabeans and soybean-based products and account for approximately 50%, 40%, and 10% of soybean-derived isoflavones, respectively. Formononetin and biochanin A are plentiful in red clover. A single plant usually contains more than one type of phytoestrogens. For instance, soybeans are rich in isoflavones, while soy sprouts are a main source of coumestrol (4).

Dietary intake of phytoestrogens has been associated with the risk of breast, endometrial, prostate, and lung cancers in previous studies (3,5). However, the associations between dietary intake of phytoestrogens and pancreatic cancer risk remains unclear. To our knowledge, only one epidemiological study has investigated the role of phytoestrogens in the etiology of pancreatic cancer. Specifically, a high intake of soy foods conferred an increased risk of pancreatic cancer in a prospective cohort study of Japanese residents, one of populations with the largest amount of soy food consumption in the world (6). The findings of that study have gained some mechanistic support from experimental studies. Soya flour feeding induced the hyperplastic foci of pancreatic acinar cells in rats and this focal neoplastic change was reversible after the feeding was discontinued (7). It was reported that phytoestrogens exhibited diverse and sex-specific effects on human pancreatic cancer cells (8, 9).

Considering the results of the experimental studies described above, we hypothesize that dietary intake of phytoestrogens is associated with an altered risk of pancreatic cancer. This hypothesis is novel and rooted in the solid biological basis. The objective of the present study is to test this hypothesis by investigating the associations between dietary intake of isoflavones and coumestrol and risk of pancreatic cancer among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The present study is expected to lead to an improved understanding of individual phytoestrogens in the etiology of pancreatic cancer and hereby to open innovative and practical avenues for its primary prevention.