A large prospective study links tea, apples, oranges, berries, and other flavonoid-rich foods with reduced breast cancer risk, including among women with elevated genetic susceptibility.
Study: Flavonoid-rich foods, genetic risk, and female breast cancer risk: a prospective cohort study. Image Credit: EngkyLatupeirissa / Shutterstock
In a recent 'Article in Press' study published in the journal npj Breast Cancer, researchers assessed the association between the flavodiet score (FDS), a measure of flavonoid-rich food intake, and breast cancer risk.
Breast cancer is among the most common malignancies worldwide, occurring predominantly in females, with an incidence approximately 100-fold greater than in males. Although traditionally considered a disease of developed countries, its incidence and mortality have significantly increased in less developed regions. Diet is a major modifiable factor that may influence breast cancer prevention, and plant-based dietary patterns have been associated with reduced cancer incidence.
Flavonoids are a family of polyphenolic compounds, commonly found in plant foods, and have multiple biological activities and antioxidant effects. Evidence suggests inverse associations between specific flavonoids (flavones, lignans, flavan-3-ols, and flavonols) and breast cancer. In addition, studies show that a higher FDS is linked to improved health outcomes, including lower dementia risk and better lung function. However, the association of the FDS with breast cancer risk remains unclear.
About the Study
In the present study, researchers investigated the association between the FDS and breast cancer risk among females and whether genetic susceptibility to breast cancer modifies the association. This study analyzed data from females in the United Kingdom Biobank (UKB). Individuals with a history of cancer except non-melanoma skin cancer, those not of White British ethnicity background, incomplete or missing dietary and genotyping data, or implausible energy intakes were excluded.
Dietary intake was assessed using the Oxford WebQ questionnaire. The United States Department of Agriculture (USDA) database was used to determine flavonoid content in foods and beverages reported in the Oxford WebQ questionnaire. Total flavonoid intake was calculated as the sum of intake of the following flavonoid sub-classes: flavanones, flavones, flavanols, flavan-3-ols, anthocyanins, proanthocyanidins, and theaflavins and thearubigins.
The FDS was the primary exposure, composed of 10 foods: tea, apples, red wine, oranges, grapes, grapefruits, dark chocolate, onions, sweet peppers, and berries. Because red wine was included in the score, the researchers also conducted sensitivity analyses that excluded it. The team selected 168 single-nucleotide polymorphisms (SNPs) associated with breast cancer at a genome-wide significance level from a prior genome-wide association study. A polygenic risk score (PRS) for breast cancer was estimated for each participant based on these SNPs.
The study’s outcome was incident breast cancer. Participants were followed up from the first dietary assessment until the diagnosis of breast cancer, death, or censoring. The associations of flavonoid-rich foods, FDS, and flavonoid sub-class intakes with breast cancer risk were assessed using Cox proportional hazards regression models. The joint effect of the FDS and PRS on the risk of breast cancer was also evaluated.
Findings
In total, 93,271 females from the UKB were included. The median follow-up time was 11.8 years, during which 3,110 incident breast cancer cases occurred. Individuals in the highest quintile of the FDS were older, more physically active, had lower body mass index (BMI), and higher household income and educational attainment than those in the lowest FDS quintile. Participants consumed a median of four servings of flavonoid-rich foods per day.
Foods in the FDS accounted for 93.7% of the total flavonoid intake. An increased FDS was associated with reduced breast cancer risk. In particular, individuals in the highest FDS quintile showed a 15% lower risk than those in the lowest quintile. Furthermore, individuals in the highest quintile of flavanone intake had a lower risk of breast cancer, although the linear trend was not statistically significant. Likewise, high intake of proanthocyanidins was associated with reduced breast cancer risk. Total flavonoid intake and other flavonoid subclasses were not significantly associated with breast cancer risk in the fully adjusted model. Results were similar when red wine was excluded from the FDS, indicating that the observed association was not driven by red wine intake.
Higher intakes of oranges and apples were associated with reduced breast cancer risk. Notably, participants with a low FDS and high genetic risk had the highest risk of breast cancer. Compared with this group, females with high genetic risk and those with low genetic risk in the highest FDS quintile had lower breast cancer risk. However, the study did not identify a statistically significant multiplicative interaction between FDS and PRS. In sub-group analyses, younger individuals and never smokers in the highest FDS quintile had reduced risk of breast cancer, as did participants with BMI ≥25 kg/m² and those with higher alcohol intake not from red wine.
Conclusions
A higher FDS was significantly associated with a lower breast cancer risk in females; the association was particularly evident among those with high genetic susceptibility to breast cancer. Moreover, higher intakes of flavanones, proanthocyanidins, oranges, and apples were inversely associated with breast cancer risk. The inverse association also remained in sensitivity analyses that excluded red wine, suggesting the finding was not driven by red wine consumption; the authors noted that alcohol consumption is not recommended for breast cancer prevention. Overall, flavonoid-rich diets were associated with lower breast cancer risk, but the observational study cannot establish causation. Further research is needed to corroborate the findings in diverse populations, clarify mechanisms, account for tumor hormone receptor subtypes, and evaluate the effects of flavonoid-rich dietary interventions.
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