Methylation of WT1, CA10 in peripheral blood leukocyte is associated with breast cancer risk: a case-control study
Menée en Chine entre 2010 et 2014 à l'aide d'échantillons sanguins collectés auprès de 402 femmes atteintes d'un cancer du sein et de 557 témoins (âge moyen : 52 ans), puis validée à l'aide de données de la cohorte EPIC-Italie portant sur 233 patientes et 340 témoins, cette étude analyse l'association entre la méthylation des gènes WT1 et CA10 des leucocytes du sang périphérique et le risque de développer la maladie
Résumé en anglais
Background: Studies have shown that abnormal changes of specific-gene DNA methylation in leukocytes may be associated with an elevated risk of cancer. However, associations between the methylation of the zinc-related genes, WT1 and CA10, and breast cancer risk remain unknown.
Methods: The methylation of WT1 and CA10 was analyzed by methylation-sensitive high-resolution-melting (MS-HRM) in a case-control study with female subjects (N = 959). Logistic regression was used to analyze the associations, and propensity score (PS) method was used to adjust confounders.
Results: The results showed that WT1 hypermethylation was associated with an increased risk of breast cancer, with an odds ratio (OR) of 3.07 [95% confidence interval (CI): 1.67–5.64, P < 0.01]. Subgroup analyses showed that WT1 hypermethylation was specifically associated with an elevated risk of luminal A subtype (OR = 2.62, 95% CI: 1.11–6.20, P = 0.03) and luminal B subtype (OR = 3.23, 95% CI: 1.34–7.80, P = 0.01). CA10 hypermethylation was associated with an increased risk of luminal B subtype (OR = 1.80, 95% CI: 1.09–2.98, P = 0.02).
Conclusion: The results of the present study suggest that the hypermethylation of WT1 methylation in leukocytes is significantly associated with an increased risk of breast cancer. The hypermethylation of WT1 is associated with an increased risk of luminal subtypes of breast cancer, and the hypermethylation of CA10 is associated with an increased risk of luminal B subtype of breast cancer.