Prohibitin 3' untranslated region polymorphism and breast cancer risk.

Introduction Prohibitin is an antiproliferative protein (1) and may function as a tumor suppressor through interaction with the retinoblastoma tumor suppressor protein and its family members (2). In addition, somatic mutations have been identified in human cancers, including breast cancer (3, 4). Interestingly, the prohibitin 3 UTR exhibits the characteristics of a trans-acting regulatory RNA that is able to arrest cell proliferation (5). A polymorphic variant allele (T allele) in the 3 UTR of prohibitin (C to T at nucleotide 1703) lacks the tumor suppressor function (6) and has been associated with an increased risk of breast cancer, particularly in women who have been diagnosed before the age of 50 years and have at least one first-degree relative with the disease (OR 4.8). However, in a subsequent study, Spurdle et al. (7) did not observe any increased risk associated with the 3 UTR T allele in a cohort of Australian women diagnosed with breast cancer before the age of 50 years. Given the important antiproliferative function that prohibitin possesses, it is plausible that the T variant could represent a cancer-predisposing allele. The frequency of the T allele is high in Caucasian populations; therefore, it could potentially contribute significantly to the population risk of breast cancer. Given the conflicting conclusions of the only two studies that have investigated this polymorphism in cancer predisposition, we conducted a case-control study among British women who had bilateral breast cancer or had a family history of breast cancer or had been diagnosed with breast cancer before the age of 40 years.