Scientists and those treating breast cancers already know a deleterious mutation in BRCA1 or BRCA2 greatly increases the lifetime risk of developing breast cancer, but until recently it remained unclear whether a correlation between lifestyle and breast cancer existed. A group of Irish researchers has now found unhealthy lifestyles may be a significant contributing factor to the increased penetrance of BRCA1 and BRCA2 mutations. They presented their results on Thursday, December 8, during the San Antonio Breast Cancer Symposium. 

Researchers at Trinity College and St. James Hospital in Dublin, Ireland, said, “Oxidative-stress and telomere dysfunction are early events in cancer development, and these processes may be considered surrogate markers of cancer risk. It has been reported that BRCA mutation carriers are more susceptible to these procarcinogenic processes than noncarriers.” 

To further explore that research, they evaluated several parameters in 75 patients from breast cancer family risk clinics and cancer genetics clinics.

  • Body-composition 
    • Body mass index
    • Waist circumference
  • Metabolic profiles
  • Physical activity (triaxial accelerometry)

In 30 patients, the researchers used enzyme-linked immunosorbent assay to measure serum levels of oxidative stress markers 8-oxo-DG and 4-HNE. Another 30 patients had telomere length measured by quantitative polymerase chain reaction.

Overall, an overwhelming majority of participants (94%) did not reach physical activity levels as recommended by the American College of Sports Medicine. The researchers also found that

  • 39% of participants were overweight.
  • 32% of participants were obese.
  • 73% of participants exhibited abdominal obesity.
  • 21% of participants had metabolic syndrome at the time of study enrollment.
  • 80% of participants presented with at least one feature of metabolic syndrome.

8-oxo-DG did not appear to be affected by body composition or metabolic syndrome status, but 4-HNE was. Serum levels of 4-HNE were significantly higher in participants with metabolic syndrome. 

Significant direct correlations between serum 4-HNE levels and waist circumference (p = 0.02), number of features of metabolic syndrome (p = 0.0007), insulin (p = 0.02), insulin resistance score (HOMA-IR, p = 0.01), HBA1c (p = 0.006), glucose (p = 0.048) and triglycerides (p < 0.0001) were all found. Age-adjusted telomere length was not a major factor.

However, moderate physical activity levels were inversely associated with age-adjusted telomere length, particularly among post-menopausal participants (p = 0.009).

The researchers concluded, “These results suggest that the potential may exist to modify procarcinogenic processes in this cohort by modifying physical activity levels and targeting the metabolic syndrome and its component features lifestyle interventions or medication.”