LEP (-2548G>A LEP) and LEPR (223Gln>Arg, 109Lys>Arg) polymorphisms as breast cancer risk factors in the Polish female population

On a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. The study involved 209 women aged 59.6 +/- 11 years diagnosed with breast cancer and 202 healthy women aged 57.8 +/- 8.2 years, who were blood donors. Polymorphism were evaluated by PCR-RFLP reaction followed by the verification of part of the samples by sequencing. The results of the study confirmed obesity as a significant breast cancer development risk factor in Polish women. However, no significant association between the studied polymorphisms and breast cancer risk or severity of the neoplastic disease was found. Interestingly, it was shown that wild type 223Gln>Gln leptin receptor (LEPR) was statistically more common in women with human epidermal growth factor receptor 2 negative (HER2-) than human epidermal groth factor receptor 2 positive (HER2+) breast cancer and wild type form of 2548G>A LEP was more common in women with progesterone receptor positive (PR+) than progesterone receptor negative (PR-) breast cancer. Studied polymorphisms of the LEP and LEPR genes do not increase breast cancer risk in the population of Polish women. However, they can affect PR an HER receptors expression and thus the severity of the disease. Noteworthy, this interesting correlation is being reported for the first time and might constitute an essential contribution to the identification of molecular mechanisms of carcinogenesis.

Automated summary

Breast cancer is the most common type of cancer in women worldwide, with obesity identified as a significant risk factor for breast cancer development in Polish women. However, the studied gene polymorphisms did not show a significant association with breast cancer risk or disease severity. Certain gene polymorphisms may affect receptor expression and disease severity, revealing a potentially important contribution to understanding the molecular mechanisms of carcinogenesis.