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Diabetes, antidiabetic medication use, and the risk of ovarian cancer

Principal Investigator
Name
Susan Steck
Degrees
PhD, MPH, RDN, FAND
Institution
University of South Carolina
Position Title
Professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-705
Initial CDAS Request Approval
Dec 21, 2020
Title
Diabetes, antidiabetic medication use, and the risk of ovarian cancer
Summary
Background: Literature suggests that diabetes mellitus, particularly type 2, is associated with the development of certain cancers. Multiple epidemiologic studies have examined the association between diabetes mellitus and risk of ovarian cancer, yielding mixed results. It is hypothesized that elevated blood glucose and insulin levels could lead to an increase in inflammation and circulating TNF-α and IGF levels, which could lead to the formation of ovarian tumors. The risk of ovarian cancer appears to be reduced when using certain anti-diabetic medications, such as metformin. Other antidiabetic medications such as insulin have been shown to increase the risk of ovarian cancer, while mixed results are presented when examining sulfonylurea and statin usage and the risk of ovarian cancer.

Public Health Significance: Understanding whether a history of diabetes can lead to an increased risk of ovarian cancer is important, specifically since the prevalence of diabetes is growing substantially and ovarian cancer is the deadliest gynecological disease in the United States. Our proposed study plans to utilize the data from PLCO to investigate the association between diabetes and ovarian cancer and investigate the association between antidiabetic
Aims

Specific Aims and Methods:
1. To examine the association between diabetes mellitus and the risk of ovarian cancer. We hypothesize that individuals with diabetes will be at higher risk of ovarian cancer compared to individuals without diabetes. We will include women who completed the BQ with complete information on diabetes status and covariates, and use the SQX to obtain data on physical activity. Cox proportional hazards regression analysis will be used to calculate hazard ratios (HRs) with their respective 95% CIs for ovarian cancer for individuals with diabetes versus those without diabetes. Two models will be created: 1) a simple model adjusting only for age and study arm, and 2) a multivariable model adjusted for selected covariates.

2. To examine the association between anti-diabetic medication use and the risk of ovarian cancer. We hypothesize that anti-diabetic medication use will be associated with reduced risk or have no association with ovarian cancer depending on the comparison group (diabetics not taking medication or non-diabetics, respectively).
We will include women with complete data on the medication use questionnaire introduced into the study in 2013. We will examine the association between anti-diabetic medication use and ovarian cancer risk with adjustment for covariates and using two separate comparison groups: 1) non-diabetics, and 2) diabetics not taking anti-diabetic medications.

In sensitivity analyses, we will stratify by the PLCO study arm and examine associations separately in the intervention and control arms to account for differences in ovarian cancer screening between arms. Person-years will be measured from the date of entry into the study until the participant has a confirmed case of ovarian cancer, until the end of follow-up, or censored from analysis due to lost to follow-up, deceased, oophorectomy, or relocated from the study site regions. Proportional hazards assumption will be tested using Schoenfeld residuals. Statistical tests will be considered significant for a p-value ≤ 0.05 and will be two-sided. SAS version 9.4 will be used for all statistical analyses.

Collaborators

Susan Steck, PhD, MPH, RDN, FAND University of South Carolina
Anthony J. Alberg, PhD, MPH University of South Carolina
Anwar T Merchant, Sc.D, MPH, DMD University of South Carolina
Jiajia Zhang, Ph.D. University of South Carolina