Send to

Choose Destination
PLoS One. 2016 Sep 15;11(9):e0162970. doi: 10.1371/journal.pone.0162970. eCollection 2016.

Effects of High-Order Interactions among IGFBP-3 Genetic Polymorphisms, Body Mass Index and Soy Isoflavone Intake on Breast Cancer Susceptibility.

Wang Q1,2, Liu L3, Li H2, Tao P4, Qi Y5, Li J2.

Author information

Department of Health Policy and Management, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
Comprehensive Guidance Center of Women's Health, Chengdu Women's and Children's Central Hospital, Chengdu, Sichuan, China.
Department of Breast Surgery, the Second People's Hospital of Sichuan Province, Chengdu, Sichuan, China.
West China Hospital, Sichuan University, Chengdu, Sichuan, China.



Polymorphisms of IGF-1 and IGFBP-3 and environmental factors may work together to influence insulin-like growth factor (IGF) levels and thus breast cancer (BC) risk. However, very few studies have investigated high-order interactions among these variables.


A total of 277 newly diagnosed BC cases and 277 controls were recruited between October 2010 and July 2012. We collected each participant's demographic characteristics, dietary intake, and blood sample. IGF-1 rs1520220 and IGFBP-3 rs2854744 were then genotyped. A multi-analytic strategy combining unconditional logistic regression (ULR), generalized multifactor dimensionality reduction (GMDR), and classification and regression tree (CART) approaches was applied to systematically identify the interactions of the two single nucleotide polymorphisms (SNPs), body mass index (BMI), and daily intake of soy isoflavone (DISI) on BC susceptibility.


In GMDR analyses, high-order interactions among BMI, DISI, and SNP rs2854744 were identified among overall and postmenopausal women. We also found significant dosage effects on BC risk with an increasing number of exposure factors, namely carrying the rs2854744 AA genotype, DISI <9.85 mg/day, and BMI ≥24 kg/m2 (P trend<0.05). Similarly, in CART analyses, compared with individuals having BMI<24kg/m2, DISI<9.85 mg/day, and the rs2854744 CC+CA genotype, BC risk increased significantly for those carrying the rs2854744 AA genotype, with BMI<24 kg/m2 and DISI<9.85 mg/day (OR = 1.95, 95%CI: 1.03-3.69), and also for those with BMI≥24kg/m2 and DISI<9.85 mg/day (OR = 2.13, 95%CI: 1.00-4.51). Similar interaction effects were observed among postmenopausal women.


This study suggests high-order interactions of the IGFBP-3 rs2854744 AA genotype, BMI≥24kg/m2, and DISI<9.85 mg/day on increased BC risk, particularly among postmenopausal women.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center