Association of the rs1346044 Polymorphism of the Werner Syndrome Gene RECQL2 with Increased Risk and Premature Onset of Breast Cancer.

Abstract

Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance of genome stability. Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types. We analyzed the association of two coding single-nucleotide polymorphisms in WRN, Cys1367Arg (rs1346044), and Arg834Cys (rs3087425), with the risk, age at onset, and clinical subclasses of breast cancer in a hospital-based case-control study of an Austrian population of 272 breast cancer patients and 254 controls. Here we report that the rare homozygous CC genotype of rs1346044 was associated with an approximately two-fold elevated breast cancer risk. Moreover, patients with the CC genotype exhibited a significantly increased risk of developing breast cancer under the age of 55 in both recessive and log-additive genetic models. CC patients developed breast cancer at a mean age of 55.2 ± 13.3 years and TT patients at 60.2 ± 14.7 years. Consistently, the risk of breast cancer was increased in pre-menopausal patients in the recessive model. These findings suggest that the CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.

• Authors: Karin Zins, Barbara Frech, Eva Taubenschuss, Christian Schneeberger, Dietmar Abraham, Martin Schreiber
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 16 Issue 12 Pg. 29643-53 (Dec 10 2015) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 26690424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Exodeoxyribonucleases
• RecQ Helicases
• WRN protein, human
• Werner Syndrome Helicase

Topics

• Age of Onset
• Breast Neoplasms (genetics)
• Case-Control Studies
• Exodeoxyribonucleases (genetics)
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Middle Aged
• Polymorphism, Single Nucleotide
• RecQ Helicases (genetics)
• Risk
• Werner Syndrome (genetics)
• Werner Syndrome Helicase