and polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families

Ann H. Rosendahl (1, 2) , Maria Hietala (1) , Maria Henningson (1) , Håkan Olsson (1, 3) , Helena Jernström (1)

1 Department of Oncology, Clinical Sciences
2 Department of Surgery, Clinical Sciences
3 Department of Cancer Epidemiology, Clinical Sciences

The insulin-like growth factor (IGF) pathway has been implicated as risk modifier in premenopausal breast cancer. In this study, associations between single nucleotide polymorphisms (SNPs) and diplotypes in the and genes and circulating IGFBP-3 levels, family status and breast cancer among women from high-risk breast cancer families were investigated. Nine and SNPs were genotyped with PCR-based methods in 323 women. Nine and ten diplotypes were identified. Plasma IGFBP-3 levels obtained during cycle day 18-23 were available for 231 women, 87 current users of combined oral contraceptives and 144 non-users. (rs1995051 and rs4988515) and (rs2471551 and rs2854744) SNPs were associated with circulating IGFBP-3 levels ( < 0.05). diplotypes were associated with lower IGFBP-3 levels and were more common in families OR 2.05 (95%CI 0.97-4.30). diplotypes were associated with higher IGFBP-3 levels and were more common in families OR 1.68 (95%CI 1.04-2.74). After adjusting the models for family status, both the and family status ( ≤ 0.006) and the diplotype GTAC/ACAT ( = 0.004) were associated with lower IGFBP-3 levels. Similarly, both the and family status ( ≤ 0.03) and the IGFBP-3 diplotypes GCA/GCG ( = 0.007) and GCG/CCG ( = 0.002) were significantly associated with lower IGFBP-3 levels, adjusted for age, weight, OC use, and other diplotypes. No individual SNP was associated with breast cancer. There were 23 cases of breast cancer and one diplotype was associated with a decreased risk of breast cancer after age 18 (log rank =0.05). In conclusion, independent effects from , diplotypes, and family status on IGFBP-3 levels were observed. These factors may influence the risk of breast cancer among women from high-risk breast cancer families.

Mots clés: IGFBP-3; Single nucleotide polymorphism; Diplotype; Breast cancer; Oral contraceptives

Ann H. Rosendahl, Maria Hietala, Maria Henningson, Håkan Olsson, Helena Jernström. and polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families. Breast Cancer Research and Treatment, 2010, 127 (3), pp.785-794. ⟨10.1007/s10549-010-1277-1⟩. ⟨hal-00615390⟩