High Dietary Phosphorus Is Associated with Increased Breast Cancer Risk in a U.S. Cohort of Middle-Aged Women

Research has shown that high amounts of dietary phosphorus that are twice the amount of the U.S. dietary reference intake of 700 mg for adults are associated with all-cause mortality, phosphate toxicity, and tumorigenesis. The present nested case-control study measured the relative risk of self-reported breast cancer associated with dietary phosphate intake over 10 annual visits in a cohort of middle-aged U.S. women from the Study of Women's Health Across the Nation. Analyzing data from food frequency questionnaires, the highest level of daily dietary phosphorus intake, >1800 mg of phosphorus, was approximately equivalent to the dietary phosphorus levels in menus promoted by the United States Department of Agriculture. After adjusting for participants' energy intake, this level of dietary phosphorus was associated with a 2.3-fold increased risk of breast cancer incidence compared to the reference dietary phosphorus level of 800 to 1000 mg, which is based on recommendations from the U.S. National Kidney Foundation, (RR: 2.30, 95% CI: 0.94-5.61, p = 0.07). Despite the lack of statistical significance, likely due to the small sample size of the cohort, the present nested case-control study's clinically significant effect size, dose-response, temporality, specificity, biological plausibility, consistency, coherence, and analogy with other research findings meet the criteria for inferred causality in observational studies, warranting further investigations. Furthermore, these findings suggest that a low-phosphate diet should be tested on patients with breast cancer.

[1]  J. Dubin,et al.  Breast cancer, alcohol, and phosphate toxicity. , 2023, Journal of applied toxicology : JAT.

[2]  Ying Lian,et al.  Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis , 2023, Frontiers in Nutrition.

[3]  H. Aoyagi,et al.  Understudied Hyperphosphatemia (Chronic Kidney Disease) Treatment Targets and New Biological Approaches , 2023, Medicina.

[4]  S. Dankel,et al.  Ultra-processed food consumption and cancer risk: A systematic review and meta-analysis. , 2023, Clinical nutrition.

[5]  J. Shin,et al.  Prospective Associations between Cumulative Average Intake of Flavonoids and Hypertension Risk in the CArdioVascular Disease Association Study (CAVAS) , 2023, Nutrients.

[6]  C. Millett,et al.  Ultra-processed food consumption, cancer risk and cancer mortality: a large-scale prospective analysis within the UK Biobank , 2023, EClinicalMedicine.

[7]  Ronald B. Brown Cancer Cachexia and Dysregulated Phosphate Metabolism: Insights from Mutant p53 and Mutant Klotho Mouse Models , 2022, Metabolites.

[8]  I. Soerjomataram,et al.  Current and future burden of breast cancer: Global statistics for 2020 and 2040 , 2022, Breast.

[9]  A. Ganti,et al.  Risk of malignancy in patients with chronic kidney disease , 2022, PloS one.

[10]  Qijun Wu,et al.  Association between dietary acid load and cancer risk and prognosis: An updated systematic review and meta-analysis of observational studies , 2022, Frontiers in Nutrition.

[11]  Zhimei Lv,et al.  Chronic Kidney Disease and Cancer: Inter-Relationships and Mechanisms , 2022, Frontiers in Cell and Developmental Biology.

[12]  A. Garg,et al.  Cancer Risk and Mortality in Patients With Kidney Disease: A Population-Based Cohort Study. , 2022, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  L. Hannibal,et al.  A Vegan Diet Is Associated with a Significant Reduction in Dietary Acid Load: Post Hoc Analysis of a Randomized Controlled Trial in Healthy Individuals , 2021, International journal of environmental research and public health.

[14]  V. Fulgoni,et al.  Trends in Total, Added, and Natural Phosphorus Intake in Adult Americans, NHANES 1988–1994 to NHANES 2015–2016 , 2021, Nutrients.

[15]  M. V. Vander Heiden,et al.  Metabolomics in cancer research and emerging applications in clinical oncology , 2021, CA: a cancer journal for clinicians.

[16]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[17]  K. Niu,et al.  A meta-analysis of the reproducibility of food frequency questionnaires in nutritional epidemiological studies , 2021, International Journal of Behavioral Nutrition and Physical Activity.

[18]  L. Arai,et al.  Do Case-Control Studies Always Estimate Odds Ratios? , 2020, American journal of epidemiology.

[19]  T. Wada,et al.  Age differences in the relationships between risk factors and loss of kidney function: a general population cohort study , 2020, BMC Nephrology.

[20]  J. Cauley,et al.  Dairy intake is not associated with improvements in bone mineral density or risk of fractures across the menopause transition: data from the Study of Women's Health Across the Nation , 2020, Menopause.

[21]  S. Crawford,et al.  Health‐related quality of life among breast cancer survivors and noncancer controls over 10 years: Pink SWAN , 2020, Cancer.

[22]  M. Orlich,et al.  Dairy, soy, and risk of breast cancer: those confounded milks. , 2020, International journal of epidemiology.

[23]  A. L. JANSE de JONGE [Adjustment]. , 2020, Nederlands tijdschrift voor de psychologie en haar grensgebieden.

[24]  J. Bacchetta,et al.  Hyperphosphatemia and Chronic Kidney Disease: A Major Daily Concern Both in Adults and in Children , 2020, Calcified Tissue International.

[25]  E. Juszczak,et al.  Application of the matched nested case-control design to the secondary analysis of trial data , 2019, BMC Medical Research Methodology.

[26]  Ronald B. Brown Vitamin D, cancer, and dysregulated phosphate metabolism. , 2019, Endocrine.

[27]  G. Colditz,et al.  Associations between dietary patterns and the risk of breast cancer: a systematic review and meta-analysis of observational studies , 2019, Breast Cancer Research.

[28]  D. Clegg,et al.  Plant-Based Diets in CKD. , 2018, Clinical journal of the American Society of Nephrology : CJASN.

[29]  R. Holden,et al.  Inorganic phosphate as a potential risk factor for chronic disease , 2018, Canadian Medical Association Journal.

[30]  F. Hayati,et al.  The relationship between chronic kidney disease and cancer , 2018 .

[31]  K. Straif,et al.  Occupational exposures and cancer: a review of agents and relative risk estimates , 2018, Occupational and Environmental Medicine.

[32]  M. Razzaque,et al.  Phosphate toxicity and tumorigenesis. , 2018, Biochimica et biophysica acta. Reviews on cancer.

[33]  M. Nestle Perspective: Challenges and Controversial Issues in the Dietary Guidelines for Americans, 1980-2015. , 2018, Advances in nutrition.

[34]  Yao-Chun Hsu,et al.  Association of chronic kidney disease with mortality risk in patients with lung cancer: a nationwide Taiwan population-based cohort study , 2018, BMJ open.

[35]  K. Shu,et al.  Risk of cancer in patients with polycystic kidney disease: a propensity-score matched analysis of a nationwide, population-based cohort study. , 2016, The Lancet. Oncology.

[36]  P. Mitchell,et al.  Chronic kidney disease and the risk of cancer: an individual patient data meta-analysis of 32,057 participants from six prospective studies , 2016, BMC Cancer.

[37]  John M Lachin,et al.  Fallacies of last observation carried forward analyses , 2016, Clinical trials.

[38]  Zachary A. Capshaw,et al.  Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology , 2015, Emerging Themes in Epidemiology.

[39]  Meghan E. Adler,et al.  Nutrient Intakes from Restaurants: What We Eat in America, NHANES 2011-2012 , 2015 .

[40]  C. Andrade Understanding relative risk, odds ratio, and related terms: as simple as it can get. , 2015, The Journal of clinical psychiatry.

[41]  A. Wolk,et al.  Milk intake and risk of mortality and fractures in women and men: cohort studies , 2014, BMJ : British Medical Journal.

[42]  E. Takeda,et al.  Estimate of dietary phosphorus intake using 24-h urine collection , 2014, Journal of clinical biochemistry and nutrition.

[43]  P. Sedgwick Nested case-control studies: advantages and disadvantages , 2014, BMJ : British Medical Journal.

[44]  B. Adams-Huet,et al.  Effects of sex and postmenopausal estrogen use on serum phosphorus levels: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 2003-2006. , 2014, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[45]  C. Ronco,et al.  Whole Grains in the Renal Diet - Is It Time to Reevaluate Their Role? , 2013, Blood Purification.

[46]  L. Appel,et al.  High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III. , 2014, The American journal of clinical nutrition.

[47]  Gail M. Sullivan,et al.  Using Effect Size-or Why the P Value Is Not Enough. , 2012, Journal of graduate medical education.

[48]  Rolf H H Groenwold,et al.  Overestimation of risk ratios by odds ratios in trials and cohort studies: alternatives to logistic regression , 2012, Canadian Medical Association Journal.

[49]  K. Sutton-Tyrrell,et al.  The SWAN song: Study of Women's Health Across the Nation's recurring themes. , 2011, Obstetrics and gynecology clinics of North America.

[50]  K. Oh,et al.  Chronic Kidney Disease in Cancer Patients: An Independent Predictor of Cancer-Specific Mortality , 2011, American Journal of Nephrology.

[51]  Gerard M Schippers,et al.  Missing Data Approaches in eHealth Research: Simulation Study and a Tutorial for Nonmathematically Inclined Researchers , 2010, Journal of medical Internet research.

[52]  B. Stengel,et al.  Chronic kidney disease and cancer: a troubling connection. , 2010, Journal of nephrology.

[53]  N. Colburn,et al.  Elevated Phosphate Activates N-ras and Promotes Cell Transformation and Skin Tumorigenesis , 2010, Cancer Prevention Research.

[54]  K. Schulz,et al.  Compared to what? Finding controls for case-control studies , 2005, The Lancet.

[55]  Neil Mann,et al.  Origins and evolution of the Western diet: health implications for the 21st century. , 2005, The American journal of clinical nutrition.

[56]  Y. Kuang,et al.  Biological stoichiometry of tumor dynamics: Mathematical models and analysis , 2003 .

[57]  Y. Kuang,et al.  Biological Stoichiometry: An Ecological Perspective on Tumor Dynamics , 2003 .

[58]  G. Eknoyan,et al.  Bone metabolism and disease in chronic kidney disease , 2003 .

[59]  R Don Gambrell,et al.  Women's Health Initiative , 2001 .

[60]  E. Turley,et al.  A new biological framework for cancer research , 1996, The Lancet.

[61]  Rajan Madhok Pollutants and pesticides may be important , 1994, BMJ.

[62]  OUP accepted manuscript , 2022, Nephrology Dialysis Transplantation.

[63]  Yi-chun Cheng,et al.  Association between chronic kidney disease and cancer including the mortality of cancer patients: national health and nutrition examination survey 1999-2014. , 2022, American journal of translational research.

[64]  D. B. Pal,et al.  Nutrients contamination and eutrophication in the river ecosystem , 2022, Ecological Significance of River Ecosystems.

[65]  K. V. Raghavaiah,et al.  A comparative study of pre- and post-menopausal breast cancer: Risk factors, presentation, characteristics and management , 2014, Journal of research in pharmacy practice.

[66]  Chris Almost,et al.  Measures of Risk , 2012 .

[67]  M. Cho,et al.  High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling. , 2009, American journal of respiratory and critical care medicine.

[68]  H. Jüppner,et al.  Endocrine Regulation of Phosphate Homeostasis , 2009 .

[69]  K. Matthews,et al.  The Study of Women's Health Across the Nation , 2009 .

[70]  L. Hutchison,et al.  BONE METABOLISM AND DISEASE IN CHRONIC KIDNEY DISEASE , 2007 .

[71]  David Morganstein,et al.  SWAN: A Multicenter, Multiethnic, Community-Based Cohort Study of Women and the Menopausal Transition , 2000 .

[72]  its Panel on Folate,et al.  STANDING COMMITTEE ON THE SCIENTIFIC EVALUATION OF DIETARY REFERENCE INTAKES , 1998 .

[73]  M. Singer,et al.  Nutritional Epidemiology , 2020, Definitions.

[74]  J K Haseman,et al.  Issues in carcinogenicity testing: dose selection. , 1985, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[75]  Rascon [The National Cancer Institute]. , 1953, Boletin cultural e informativo - Consejo General de Colegios Medicos de Espana.