Single nucleotide polymorphisms in the Leptin gene as potential biomarkers of breast cancer prognosis

Breast cancer is the second most incident neoplasm and the leading cause of cancer deaths in women worldwide (BRAY et al. CA Cancer J Clin. 2024; 74: 229.). Obesity has been implicated with worse outcomes (CRISPO et al. Sci Rep 2023;13: 21208.), and a metanalysis proposes leptin levels as a potential prognostic biomarker (JIN et al. Medicine, 2021; 100: 33.). Here, we investigate a single nucleotide polymorphism within the leptin gene (rs7799039) among breast cancer patients. A prospective cohort was conducted at Hospital do Câncer III/INCA with women with primary non-metastatic breast cancer (N = 1038). The study protocol was approved by the INCA Ethics Committee (#129/08).  Genomic DNA was used for genotyping by real-time PCR. Histopathological and clinical follow-up data were obtained from electronic medical records. Allelic and genotypic frequencies were derived by gene counting, and tested for Hardy–Weinberg equilibrium (HWE) with the Chi-square test for goodness-of-fit. The distribution of genotypes was evaluated using the Chi-square or Fisher’s exact tests. The influence of individual variable on survival outcomes were estimated using Kaplan-Meier curves with the two-sided Log-Rank test. Genotyping of rs7799039 was performed for 609 of 820 available DNA samples, with a success recovery rate of 91%. The genotypic distribution fitted HWE (p = 0.22), with 60 AA (10.8%), 264 AG (47.6%) and 231 GG (41.6%), and a minor allelic frequency (A) of 34.6%. Such allelic frequency varied significantly (p < 0,0001 according to self-declared skin color/race, being higher among persons who referred themselves as white (41%), as compared to those who referred as brown (32%) or black (20%). Regarding survival analyses, total patient follow-up was 98,053 person-months, with a median follow-up time per person of 96 months. No significant independent effects of rs7799039 were detected on survival outcomes, either considering the whole population or only obese patients.