Margaret Hoyt

M.P.H., M.S.

Indiana University

PhD Student

PLCO (Learn more about this study)

PLCO-404

Oct 4, 2018

Interaction of Calcium Intake and Obesity on Pancreatic Cancer in the PLCO Trial

Pancreatic cancer is the third leading cause of cancer-related deaths in both men and women in the United States (1). This disease has a dismal prognosis as most cases are diagnosed at an advanced stage. No effective screening test is available for early detection of pancreatic cancer; thus, prevention remains a priority. To date, little is known about the etiology of pancreatic cancer, apart from family history, diabetes, and smoking status (2). Therefore, it is critical to identify modifiable risk factors for the primary prevention of pancreatic cancer, such as diet. The objectives of our proposed research are: 1) Investigate intake of calcium, BMI, and their interaction in relation to pancreatic cancer risk; 2) Evaluate the association of BMI trajectories over time with pancreatic cancer; and 3) Examine the associations of intake of calcium, magnesium, phosphorus, and potassium with pancreatic cancer risk.
Calcium plays an important role in modulation of obesity, partially controlled by secretion of Ca2+ by the pancreas. Sulfonylurea receptors (SUR) on the pancreas control the Ca2+ channels that influence changes in adiposity (3); prolonged increase of Ca2+ can lead to pancreatic injury (4). Previous studies have explored the association between calcium intake and pancreatic cancer risk, with inconsistent results (5,6,7). Data on intake of energy, calcium, and other nutrients, as well as body weight and height, have been collected from more than 500 cases of pancreatic cancer and a large population of healthy subjects in the PLCO trial. This database presents a unique opportunity for us to accomplish this objective.
The association between obesity and pancreatic cancer has been investigated in some epidemiological studies, but the majority measure BMI only once. Meta-analyses of this research have shown an overall trend toward a positive relationship, however the increase in risk was relatively small (8,9). As pancreatic cancer has a long latent period, BMI over a long period of time may be more indicative of actual risk associated with obesity. Previous research found a positive association between increased life-long body shape trajectory and pancreatic cancer; however, this finding was not statistically significant. The authors site the relatively low number of people in some body-shape groups and small differences between body shape as limitations (10). We were unable to identify any other studies examining this relationship, indicating the need for additional research. As the PLCO collects three data points for BMI over time, it is an ideal data-set to examine this association.
The proposed research also seeks to comprehensively investigate the effects of intake of calcium, magnesium, phosphorus, and potassium and their potential interactions on pancreatic cancer risk. Several studies have suggested that dietary intake of calcium, magnesium, and potassium may play a role in carcinogenesis (13,14). Conversely, reduced dietary intake of phosphorus possibly leads to reduced risk of prostate cancer, due to an increase in levels of 1,25 (OH)2D (15,16). Identification of modifiable dietary and lifestyle risk factors will provide valuable insight towards the development of effective primary prevention of pancreatic cancer.

Specific Aim 1: To investigate the interaction between dietary calcium intake and obesity on pancreatic cancer risk.

Specific Aim 2: To investigate the impact of different BMI trajectories on pancreatic cancer risk.

Specific Aim 3: To investigate the association between dietary intake of calcium, magnesium, phosphorus, and potassium on pancreatic cancer risk in the PLCO population.