Amanda Leiter

M.D., M.S.

Icahn School of Medicine at Mount Sinai

Fellow

PLCO (Learn more about this study)

PLCO-668

Sep 22, 2020

The impact of diabetes on lung cancer incidence and prognosis according to histologic subtype

Diabetes is a risk factor and poor prognostic factor for many types of malignancies. However, the relationship between diabetes and non-small cell lung cancer (NSCLC) incidence and prognosis is not well-established and past data has been conflicting. The incidence of diabetes has been increasing in recent years, with prevalence most recently reported as 13.5% in US adults and 21.4% in adults older than 65 years old(1). Given the high prevalence of diabetes, particularly in older adults, establishing how diabetes impacts NSCLC risk and outcomes is important for enhancing screening efforts and identifying targeted efforts to treat NSCLC in patients who have diabetes.

Emerging laboratory and epidemiologic data suggest that different NSCLC histologic subtypes may vary in regard to how they are impacted by high glucose levels. Preclinical data has demonstrated that squamous cell carcinoma has elevated glucose transporter 1 (GLUT1) expression compared to adenocarcinoma and is more reliant on glucose metabolism for growth (2). Additionally, an epidemiologic study demonstrated that patients exposed to high glycemic index diets are at higher risk for squamous cell carcinomas, but not other histologic subtypes of NSCLC (3).

The impact of diabetes on NSCLC risk and prognosis according to histologic subtype has not been established in large clinical datasets. With this project, we aim to assess the relationship between metabolic comorbidities and lung cancer histology and stage at diagnosis. We also aim to assess the impact of metabolic diseases on lung cancer survival according to histology. Knowing how diabetes may influence NSCLC subtype has important implications for targeted screening and treatment efforts for patients with diabetes.

References:
1. National Diabetes Statistics Report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2020.
2. Goodwin J, Neugent ML, Lee SY, Choe JH, Choi H, Jenkins DMR, Ruthenborg RJ, Robinson MW, Jeong JY, Wake M, Abe H, Takeda N, Endo H, Inoue M, Xuan Z, Yoo H, Chen M, Ahn JM, Minna JD, Helke KL, Singh PK, Shackelford DB, Kim JW. The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition. Nature communications. 2017;8:15503.
3. Melkonian SC, Daniel CR, Ye Y, Pierzynski JA, Roth JA, Wu X. Glycemic Index, Glycemic Load, and Lung Cancer Risk in Non-Hispanic Whites. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2016;25(3):532-53

1. Assess the impact of diabetes on lung cancer incidence according to histologic subtype.

2. Determine the impact of diabetes on lung cancer-specific mortality according to histologic subtype.