Dados do Resumo

Título

Pivotal Role of Oxidative Stress and Inflammation in Increased Risk of Luminal A Breast Cancer Independent of Menopause and Obesity: Case-Control Study

Introdução

Breast cancer (BC) is the most prevalent cancer globally and the leading cause of cancer-related mortality in women. It is urgent to understand the risk factors that can contribute to the increased incidence. Luminal A is the most prevalent subtype and estrogen, through ER binding and activation of the PI3K/Akt pathway, promotes tumor growth. Obesity exacerbates BC aggressiveness via chronic inflammation, oxidative stress, elevated insulin levels and positive stimulus to estrogen synthesis via aromatase pathway.

Objetivo

We aim to investigate the impact of metabolic biomarkers, specifically glucose metabolism, oxidative stress, and inflammation, on the risk of Luminal A BC, providing insights into how these factors contribute to breast carcinogenesis.

Métodos

This study included 47 women with Luminal A BC and 100 matching controls and was approved by the Research Ethics Committees of the General Hospital of Fortaleza (050507/10) and the School of Public Health USP (2162). All women provided informed written consent before starting study. Sociodemographic data and risk factors were obtained from medical records. The anthropometric assessment was performed by a trained researcher. Insulin, IGF-1 and adiponectin were assessed using standard ELISA kits. Glucose was analyzed by colorimetric method. The plasma lipid peroxidation to asses TBARS was performed according to the method proposed by Ohkawa et al. (1979). The inflammatory markers (IL6, IL1β, TNF-α, MCP-1 and IL10) were measured using the commercial Human Magnetic Panel Bead Milliplex® MAP kit. Statistical significance was set at p < 0.05.

Resultados

Individuals were similar regarding menopause status and BC risk factors (HRT, nulliparity, breastfeeding, smoking and alcohol). Both groups were overweight/obese with similar lean and fat mass. Women in Luminal A BC had higher waist circumference (WC) than control group (91.2 ± 10.1 cm vs. 95.7 ± 10.2cm; p = 0.020). At diagnosis, Luminal A BC patients had higher TBARS, glucose, IGF-1, IL1β and IL6 whereas anti-inflammatory marker (IL10) was lower. TBARS was associated with increased odds to have Luminal A BC (OR = 3.133; CI95% = 1.581 – 6.210), even after adjustment for menopause status and BMI (AOR = 3.291; CI95% = 1.621 – 6.642). Similarly, significant association was found with glucose and insulin in both unadjusted and adjusted models for menopausal status and BMI (AOR = 6.106; CI95% = 2.773 – 13.444 and AOR = 3.057; CI95% = 1.235 – 7.569, respectively). Adiponectin was protective on Luminal A BC in the unadjusted model (OR = 0.469; CI95% = 0.238 – 0.925) and after adjustment for menopause (OR = 0.479; CI95% = 0.242 –0.947). Higher levels of IL10 were related to reduced risk after simultaneous adjustment for menopausal status and BMI (AOR = 0.263; CI95% = 0.102 – 0.683).

Conclusões

Women diagnosed with Luminal A BC had impaired inflammatory biomarkers, oxidative stress, adiponectin, and alterations in the insulin/IGF axis. Elevated glucose, insulin, and TBARS levels significantly increase risk of developing Luminal A BC, independent of menopausal status and BMI, while IL10 is protective. We speculate that the serum estrogen and ER expression in the cell surface create an environment to breast carcinogenesis by stimulus of oxidative and inflammatory pathways.

Financiador do resumo

This work was supported by the State of São Paulo Research Foundation - FAPESP under Grant number 2016/24531-3; 2018/18739-6; CAPES under Grant number 88882.330835/2019-01.

Palavras Chave

Breast cancer; Risk factor; Oxidative Stress