Risk reduction through dietary modifications is an adjunct strategy for prevention of oesophageal cancer, a leading cause of cancer-related mortality and morbidity worldwide. We aimed to estimate the association between calcium and magnesium intakes and incident oesophageal cancer (OC).
We conducted a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort. We used multivariable Cox proportional hazard modeling to estimate the association between total intakes and incident OC overall and by histology (oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC)). Sensitivity and stratified analyses were performed.
Among 536,359 included respondents, 1414 incident OCs occurred over 6.5 million person-years follow-up time. Increasing dietary calcium intake was associated with an adjusted 32–41% lower risk of OSCC compared to the lowest quartile (p-trend 0.01). There was a positive association between increasing magnesium intake and OAC risk, but only among participants with low calcium:magnesium intake ratios (p-trend 0.04). There was a significant interaction with smoking status.
Based on a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort, dietary intakes of calcium and magnesium were significantly associated with risk of OSCC and, among certain participants, OAC, respectively. If validated, these findings could inform dietary modifications among at-risk individuals. Mechanistic investigations would provide additional insight.
Subscribe to Journal
Get full journal access for 1 year
only $20.79 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. & Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).
National Cancer Institute, Surveillance, Epidemiology, and End Results Program. Esophageal Cancer - Cancer Stat Facts. https://seer.cancer.gov/statfacts/html/esoph.html. (2019)
American Gastroenterological Association, Spechler, S. J., Sharma, P., Souza, R. F., Inadomi, J. M. & Shaheen, N. J. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology 140, 1084–1091 (2011).
Shaheen, N. J., Falk, G. W., Iyer, P. G. & Gerson, L. B., American College of Gastroenterology. ACG clinical guideline: diagnosis and management of barrett’s esophagus. Am. J. Gastroenterol. 111, 30–50 (2016).
McCormack, V. A., Menya, D., Munishi, M. O., Dzamalala, C., Gasmelseed, N., Leon Roux, M. et al. Informing etiologic research priorities for squamous cell esophageal cancer in Africa: a review of setting-specific exposures to known and putative risk factors. Int J. Cancer 140, 259–271 (2017).
Dong, J.-Y., Xun, P., He, K. & Qin, L.-Q. Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies. Diabetes Care. 34, 2116–2122 (2011).
Champagne, C. M. Magnesium in hypertension, cardiovascular disease, metabolic syndrome, and other conditions: a review. Nutr. Clin. Pr. 23, 142–151 (2008).
Dai, Q., Cantwell, M. M., Murray, L. J., Zheng, W., Anderson, L. A., Coleman, H. G. et al. Dietary magnesium, calcium:magnesium ratio and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case-control study. Br. J. Nutr. 115, 342–350 (2016).
Dai, Q., Shu, X.-O., Deng, X., Xiang, Y.-B., Li, H., Yang, G. et al. Modifying effect of calcium/magnesium intake ratio and mortality: a population-based cohort study. BMJ Open. 3, 1–14 (2013).
Wark, P. A., Lau, R., Norat, T. & Kampman, E. Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis. Am. J. Clin. Nutr. 96, 622–631 (2012).
Dai, Q., Motley, S. S., Smith, J. A., Concepcion, R., Barocas, D., Byerly, S. et al. Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer. PLoS ONE. 6, e18237 (2011).
Shah, S. C., Dai, Q., Zhu, X., Peek, R. M., Smalley, W., Roumie, C. et al. Associations between calcium and magnesium intake and the risk of incident gastric cancer: a prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Int. J. Cancer. (2019). [Epub ahead of print]. https://doi.org/10.1002/ijc.32659.
Hashemian, M., Poustchi, H., Abnet, C. C., Boffetta, P., Dawsey, S. M., Brennan, P. J. et al. Dietary intake of minerals and risk of esophageal squamous cell carcinoma: results from the Golestan Cohort Study. Am. J. Clin. Nutr. 102, 102–108 (2015).
Park, Y., Leitzmann, M. F., Subar, A. F., Hollenbeck, A. & Schatzkin, A. Dairy food, calcium, and risk of cancer in the NIH-AARP Diet and Health Study. Arch. Intern Med 169, 391–401 (2009).
Schatzkin, A., Subar, A. F., Thompson, F. E., Harlan, L. C., Tangrea, J., Hollenbeck, A. R. et al. Design and serendipity in establishing a large cohort with wide dietary intake distributions: the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Am. J. Epidemiol. 154, 1119–1125 (2001).
Thompson, F. E., Kipnis, V., Midthune, D., Freedman, L. S., Carroll, R. J., Subar, A. F. et al. Performance of a food-frequency questionnaire in the US NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study. Public Health Nutr. 11, 183–195 (2008).
Dai, Q., Shrubsole, M. J., Ness, R. M., Schlundt, D., Cai, Q., Smalley, W. E. et al. The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. Am. J. Clin. Nutr. 86, 743–751 (2007).
Dai, Q., Sandler, R., Barry, E., Summers, R., Grau, M. & Baron, J. Calcium, magnesium, and colorectal cancer. Epidemiology 23, 504–505 (2012).
Michaud, D., Midthune, D., Hermansen, S., Leitzmann, M., Harlan, L. C., Kipnis, V. et al. Comparison of cancer registry case ascertainment with SEER estimates and self‐reporting in a subset of the NIH‐AARP Diet and Health Study. J. Registry Manag. 32, 70–75 (2005)
Center for Nutrition Policy and Promotion. Healthy Eating Index (HEI). https://www.cnpp.usda.gov/healthyeatingindex. (United States Department Of Agriculture, 2019)
Li, W.-Q., Park, Y., Wu, J. W., Ren, J.-S., Goldstein, A. M., Taylor, P. R. et al. Index-based dietary patterns and risk of esophageal and gastric cancer in a large cohort study. Clin. Gastroenterol. Hepatol. 11, 1130–1136.e2 (2013).
Willett, W. & Stampfer, M. J. Total energy intake: implications for epidemiologic analyses. Am. J. Epidemiol. 124, 17–27 (1986).
Li, Q., Cui, L., Tian, Y., Cui, H., Li, L., Dou, W. et al. Protective effect of dietary calcium intake on esophageal cancer risk: a meta-analysis of observational studies. Nutrients. 9, 1–11 (2017)
Wulaningsih, W., Michaelsson, K., Garmo, H., Hammar, N., Jungner, I., Walldius, G. et al. Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study. BMC Public Health 13, 663 (2013).
Peacock, M. Calcium metabolism in health and disease. Clin. J. Am. Soc. Nephrol. 5(Suppl. 1), S23–S30 (2010).
Bailey, R. L., Dodd, K. W., Goldman, J. A., Gahche, J. J., Dwyer, J. T., Moshfegh, A. J. et al. Estimation of total usual calcium and vitamin D intakes in the United States. J. Nutr. 140, 817–822 (2010).
Health.gov. 2015–2020 Dietary Guidelines - health.gov. https://health.gov/dietaryguidelines/2015/guidelines/. (2018)
Zhu, X., Shrubsole, M. J., Ness, R. M., Hibler, E. A., Cai, Q., Long, J. et al. Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study. Mol. Carcinog. 55, 1449–1457 (2016).
Wolf, F. I., Maier, J. A. M., Nasulewicz, A., Feillet-Coudray, C., Simonacci, M., Mazur, A. et al. Magnesium and neoplasia: from carcinogenesis to tumor growth and progression or treatment. Arch. Biochem Biophys. 458, 24–32 (2007).
Iseri, L. T. & French, J. H. Magnesium: nature’s physiologic calcium blocker. Am. Heart J. 108, 188–193 (1984).
Bussière, F. I., Gueux, E., Rock, E., Mazur, A. & Rayssiguier, Y. Protective effect of calcium deficiency on the inflammatory response in magnesium-deficient rats. Eur. J. Nutr. 41, 197–202 (2002).
Ford, E. S. & Mokdad, A. H. Dietary magnesium intake in a national sample of US adults. J. Nutr. 133, 2879–2882 (2003).
Ethics approval and consent to participate
The study was approved by the Special Studies Institutional Review Board of the US National Cancer Institute (NCI). Original consent from participants was obtained from investigators for the NIH-AARP Diet and Health Study at enrolment. No new data collection or participant contact occurred for the purposes of this study.
Consent for publication
Not applicable. No individual-level data are included in this paper.
The data that support the findings of this study are available from the NIH-AARP Diet and Health Study. Restrictions apply to the availability of these data, which were used under license for this study. Data are available with the permission of the NIH AARP.
The authors declare no competing interests.
Research reported in this publication was supported by the Agency for Healthcare Research (AHRQ) and Quality and Patient-Centered Outcomes Research Institute (PCORI) under Award Number K12 HS026395, awarded to SCS. The content is solely the responsibility of the listed authors and does not necessarily represent the official views of AHRQ or PCORI.
Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Shah, S.C., Dai, Q., Zhu, X. et al. Associations between calcium and magnesium intake and the risk of incident oesophageal cancer: an analysis of the NIH-AARP Diet and Health Study prospective cohort. Br J Cancer 122, 1857–1864 (2020). https://doi.org/10.1038/s41416-020-0818-6
Current Opinion in Gastroenterology (2021)
Perspective: Characterization of Dietary Supplements Containing Calcium and Magnesium and Their Respective Ratio—Is a Rising Ratio a Cause for Concern?
Advances in Nutrition (2020)