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ATM missense variant P1054R predisposes to prostate cancer

Andreas Meyer1, Bettina Wilhelm, Thilo Dörk

  • 1Department of Radiation Oncology, Hannover Medical School, Germany. andie.meyer@gmx.net

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
|May 16, 2007
PubMed
Abstract

Insights

The ATM gene variant P1054R is linked to a twofold increased risk of prostate cancer. This genetic variant does not appear to increase the risk of adverse radiotherapy side effects in patients with early-stage prostate cancer.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Prostate cancer is characterized by impaired DNA repair, leading to genetic instability.
  • The ATM gene is crucial for cell cycle regulation and maintaining genomic integrity.
  • Investigating ATM gene variants can shed light on prostate cancer development and progression.

Purpose of the Study:

  • To determine if the ATM missense substitution P1054R is more prevalent in prostate cancer patients.
  • To assess if carriers of the P1054R variant face a higher risk of treatment-related side effects.
  • To explore the association of the ATM F858L variant with prostate cancer risk and treatment outcomes.

Main Methods:

  • A case-control study involving 261 early-stage prostate cancer patients treated with I-125 brachytherapy and 460 male controls.
  • Screening for the ATM P1054R variant in both patient and control groups.
  • Prospective assessment of treatment morbidity using validated questionnaires (IPSS, QoL, IIEF-15) to compare carriers and non-carriers.

Main Results:

  • The P1054R variant was significantly more common in prostate cancer patients (2.1-fold increased risk).
  • The ATM F858L variant, found in a subset of P1054R carriers, also showed a similar increased risk.
  • No significant differences in IPSS, QoL, or erectile function (IIEF-15) were observed between carriers and non-carriers after 18 months of follow-up.

Conclusions:

  • The ATM P1054R variant is associated with a doubled risk of prostate cancer in the studied cohort.
  • The co-occurrence of the F858L variant does not confer a significantly higher risk.
  • No increased adverse radiotherapy response was detected in P1054R carriers after 18 months.

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