Abstract
BackgroundPolymorphisms 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.MethodsA 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.ResultsIn 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.ConclusionsThis 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.
Highlights
Breast cancer (BC) is common among women worldwide, with about1.67 million new cases diagnosed in 2012, accounting for 25% of all cancers [1]
We found significant dosage effects on breast cancer (BC) risk with an increasing number of exposure factors, namely carrying the rs2854744 AA genotype, daily intake of soy isoflavone (DISI)
This study suggests high-order interactions of the IGFBP-3 rs2854744 AA genotype, BMI!24kg/m2, and DISI
Summary
Breast cancer (BC) is common among women worldwide, with about1.67 million new cases diagnosed in 2012, accounting for 25% of all cancers [1]. In China, the incidence of BC has steadily risen, from 126,227 in 2002 [2] to over 169,000 in 2008 [3], to 187,213 in 2012 [1] Unless this trend slows, BC cases in China are expected to reach 2.5 million overall by 2021[4]. The insulin-like growth factor (IGF) system plays important roles in cellular proliferation, differentiation, and apoptosis [5,6,7]; the IGF system has long been known to be involved in BC carcinogenesis. Within the IGF system, IGF-1 and IGFBP-3 are two key subunits involved in carcinogenesis. Polymorphisms of IGF-1 and IGFBP-3 and environmental factors may work together to influence insulin-like growth factor (IGF) levels and breast cancer (BC) risk. Very few studies have investigated high-order interactions among these variables.
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