Insulinemic potential of diet and risk of total and subtypes of breast cancer among US females

Andrea Romanos-Nanclares; Fred K Tabung; Walter C Willett; Bernard Rosner; Michelle D Holmes; Wendy Y Chen; Rulla M Tamimi; A Heather Eliassen

doi:10.1093/ajcn/nqac284

Insulinemic potential of diet and risk of total and subtypes of breast cancer among US females

Am J Clin Nutr. 2022 Dec 19;116(6):1530-1539. doi: 10.1093/ajcn/nqac284.

Authors

Andrea Romanos-Nanclares¹, Fred K Tabung^{2

3

4}, Walter C Willett^{1

2

5}, Bernard Rosner^{1

6}, Michelle D Holmes^{1

5}, Wendy Y Chen^{1

7}, Rulla M Tamimi⁸, A Heather Eliassen^{1

2

5}

Affiliations

¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
² Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Division of Medical Oncology, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
⁴ The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.
⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁶ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.

Abstract

Background: Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diets with higher insulinemic potential increase the risk of invasive breast cancer.

Objectives: We aimed to prospectively evaluate the association between a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer.

Methods: We prospectively followed 76,686 women from the Nurses' Health Study (NHS; 1984-2016) and 93,287 women from the Nurses' Health Study II (NHSII; 1991-2017). Diet was assessed by food-frequency questionnaires every 4 y. The insulinemic potential of diet was evaluated using the previously established EDIH based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential of the diet. Covariates included reproductive, hormonal, and anthropometric factors (height and BMI at age 18 y); race; socioeconomic status; total alcohol intake; total caloric intake; and physical activity.

Results: During 4,216,106 person-years of follow-up, we documented 10,602 breast cancer cases (6689 NHS, 3913 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIH quintile (Q) were at higher breast cancer risk (HRQ5 vs. Q1 = 1.15; 95% CI: 1.07, 1.24; P-trend < 0.01). Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association between EDIH and breast cancer was observed for ER-negative tumors (HRQ5 vs. Q1 = 1.21; 95% CI: 1.00, 1.46; P-trend = 0.02). Among tumor molecular subtypes, the strongest associations were observed for human epidermal growth factor receptor 2 (HER2)-enriched tumors (HRQ5 vs. Q1 = 1.62; 95% CI: 1.01, 2.61; P-trend = 0.02).

Conclusions: A dietary pattern contributing to hyperinsulinemia and insulin resistance was associated with greater breast cancer risk, especially ER-negative and HER2-enriched tumors. Our findings suggest that dietary modifications to reduce insulinemic potential may reduce the risk of breast cancer.

Keywords: breast cancer; cohort study; diet; dietary patterns; epidemiology; hyperinsulinemia.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Breast Neoplasms* / epidemiology
Breast Neoplasms* / etiology
Diet
Energy Intake
Female
Humans
Hyperinsulinism*
Insulin Resistance*
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding