The association between androgen receptor CAG gene polymorphism and pubertal gynecomastia

Androgen signaling is essential in mammary gland homeostasis.CAG repeat length polymorphism of the androgen receptor (AR) gene was shown to be a predisposing factor in the development of breast cancer. In the light of previous studies we hypothesized that in men with long AR CAG repeats, the decreased activity of AR within the breast tissue by leading into a relative increase in estrogenic activity, increased aromatization of androgens to estrogens due to substrate excess, and increased skinfold thickness and BMI leading to a raise in the peripheral aromatase activity might cause gynecomastia. The aim of this study was to evaluate the association between pubertal gynecomastia and AR gene CAG repeat polymorphism. Methods: We enrolled 101 adolescents with pubertal gynecomastia between 12 to 19 years of age and 88 healthy controls without a history of gynecomastia, at least 14 years of age and with a pubertal stage of Tanner 4 to 5. The specific AR CAG repeat length of the individuals was analyzed with DNA sequence analysis. There was no association between AR CAG repeat length and gynecomastia. The limited number of cases, lack of evaluation according to pubertal stage, self-reported gynecomastia history in the control group, and cross-sectional design of the study are among the limitations. Therefore, the results obtained from this study are not sufficient to evaluate the effects of changes in the length of AR gene CAG length on AR functions. The analysis of AR gene CAG repeat length polymorphism, together with other potential polymorphisms modulating AR activity and androgen levels, in larger series might confirm the hypothesis of this study. Key words: Pubertal gynecomastia, AR CAG repeat length polymorphism This study was funded by Hacettepe University Scientific Research Projects Coordination Unit.