Abstract

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells. However, recent data on LRP1 suggest that this receptor can also be involved in tumor establishment and progression. We investigated an association between the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any cancer disease. An increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112-2.732). The T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin.

Highlights

  • The low-density lipoprotein receptor-related protein 1 (LRP1, ID 6692 in the Human Gene Nomenclature database) is a member of the low-density lipoprotein receptor (LDLR) family [1]

  • An increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963)

  • The T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin

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Summary

Introduction

The low-density lipoprotein receptor-related protein 1 (LRP1, ID 6692 in the Human Gene Nomenclature database) is a member of the low-density lipoprotein receptor (LDLR) family [1]. Receptors of this family mediate the internalization of a variety of extracellular macromolecules and macromolecular complexes, including lipoproteins, proteinases, proteinase–inhibitor complexes and extracellular matrix proteins [2]. Through the regulation of extracellular proteolytic activity, LRP1 has an important role in the regulation of cellular growth, cell migration, tissue repair and remodeling, and tumor progression and invasion [1,3,6]. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Recent data on LRP1 suggest that this receptor can be involved in tumor establishment and progression

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