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We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom  = 3.05, 95%CI = 1.72-5.44, Phom  = 1.47 × 10-4 ), MAST2-rs12124649 (ORhom  = 1.73, 95% CI =1.18-2.54, Phom  = 5.24 × 10-3 ), and INSR-rs10500204 (ORhom  = 1.96, 95% CI = 1.44-2.67, Phom =1.68 × 10-5 ) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom  = 1.78, 95% CI = 1.30-2.44, Phom  = 3.23 × 10-4 ). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.

Original publication




Journal article


Int J Cancer

Publication Date





1182 - 1188


BPC3, breast cancer in situ, genetic epidemiology, single nucleotide polymorphisms, Activin Receptors, Type II, Aged, Antigens, CD, Breast Carcinoma In Situ, Breast Neoplasms, Case-Control Studies, Female, Genetic Predisposition to Disease, Gonadal Steroid Hormones, Humans, Insulin-Like Growth Factor I, Introns, Microtubule-Associated Proteins, Middle Aged, Polymorphism, Single Nucleotide, Promyelocytic Leukemia Protein, Prospective Studies, Protein-Serine-Threonine Kinases, Receptor, Insulin