SPIRE1 and cancer: One CpG with decreased methylation in incumbent firefighters, that was statistically significant until additionally adjusted for BMI (Table 2), is located in the promoter region of SPIRE1. The dysregulated expression of the protein encoded by this gene, SPIRE1, has been associated with cellular potential for extracellular matrix degradation, which may impact the invasive and metastatic behavior of cancer cells [51].