Higher diet-dependent acid load is associated with risk of breast cancer: Findings from the sister study

Int J Cancer. 2019 Apr 15;144(8):1834-1843. doi: 10.1002/ijc.31889. Epub 2018 Dec 7.


Dietary factors that contribute to chronic low-grade metabolic acidosis have been linked to breast cancer risk, but to date no epidemiologic study has examined diet-dependent acid load and breast cancer. We used data from 43,570 Sister Study participants who completed a validated food frequency questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. The Potential Renal Acid Load (PRAL) score was used to estimate diet-dependent acid load. Higher scores reflect greater consumption of protein and phosphorus, and lower consumption of potassium, calcium and magnesium. The association between PRAL and breast cancer was evaluated using multivariable Cox proportional hazards regression. We identified 1,614 invasive breast cancers diagnosed at least 1 year after enrollment (mean follow-up, 7.6 years). The highest PRAL quartile, reflecting greater acid-forming potential, was associated with increased risk of breast cancer (HRhighest vs. lowest quartile : 1.21 [95% CI, 1.04-1.41], ptrend = 0.04). The association was more pronounced for estrogen receptor (ER)-negative (HRhighest vs. lowest quartile : 1.67 [95% CI, 1.07-2.61], ptrend = 0.03) and triple-negative breast cancer (HRhighest vs. lowest quartile : 2.20 [95% CI, 1.23-3.95], ptrend = 0.02). Negative PRAL scores, representing consumption of alkaline diets, were associated with decreased risk of ER-negative and triple-negative breast cancer, compared to a PRAL score of 0 representing neutral pH. Higher diet-dependent acid load may be a risk factor for breast cancer while alkaline diets may be protective. Since PRAL scores are positively correlated with meat consumption and negatively correlated with fruit and vegetable intake, results also suggest that diets high in fruits and vegetables and low in meat may be protective against hormone receptor negative breast cancer.

Keywords: ER-negative breast cancer; breast cancer; diet-dependent acid load; potential renal acid load; triple-negative breast cancer.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Acidosis / complications*
  • Acidosis / etiology
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / etiology
  • Feeding Behavior*
  • Female
  • Follow-Up Studies
  • Fruit
  • Humans
  • Hydrogen-Ion Concentration
  • Meat / adverse effects
  • Middle Aged
  • Nutrition Assessment
  • Prospective Studies
  • Risk Factors
  • Siblings*
  • Surveys and Questionnaires / statistics & numerical data
  • Vegetables