Methylome analysis and epigenetic changes associated with menarcheal age

Area of Science:

• Epigenetics
• Reproductive Epidemiology
• Cancer Etiology

Background:

• Reproductive factors influence breast cancer risk and DNA methylation.
• DNA methylation is a key mechanism linking reproductive factors to disease.
• Few human studies explore the relationship between reproductive factors and DNA methylation.

Purpose of the Study:

• To investigate the association between reproductive factors and genome-wide DNA methylation in healthy women.
• To examine the link between age at menarche and DNA methylation patterns.
• To explore potential epigenetic mechanisms influenced by early life events.

Main Methods:

• Genome-wide DNA methylation analysis using LUminometric Methylation Assay (LUMA) in 376 women (EPIC study).
• CpG site methylation analysis using Infinium HumanMethylation 450 BeadChip in 332 women (EPIC-Italy sub-cohort).
• Multivariate logistic and linear regression models to assess associations with reproductive risk factors.

Main Results:

• Age at menarche showed an inverse association with global DNA methylation (LUMA).
• Increased age at menarche correlated with a higher risk of below-median global methylation.
• No significant association was found between menarcheal age and global methylation using Illumina technology; only one CpG site showed a significant difference, which was not replicated.

Conclusions:

• A link exists between age at menarche and genome-wide DNA methylation, particularly repetitive element methylation.
• The discrepancy between LUMA and Illumina results suggests repetitive element methylation plays a role.
• Epigenetic changes may be modulated by menarcheal age, or reflect broader early-life influences on both methylation and menarcheal timing.