Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study

BMC Public Health

Mieke Van Hemelrijck⁷  Lars Holmberg³  Mats Lambe⁶  Göran Walldius¹  Ingmar Jungner²  Niklas Hammar⁵  Hans Garmo³  Karl Michaelsson⁸  Wahyu Wulaningsih⁴ 

[1] Department of Epidemiology, Insitute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden;Department of Medicine, Clinical Epidemiological Unit, Karolinska Institutet and CALAB Research, Stockholm, Sweden;Regional Cancer Centre, Uppsala University, Uppsala, Sweden;King’s College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, London, UK;AstraZeneca Sverige, Södertalje, Sweden;Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;King’s College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, Research Oncology, 3rd Floor, Bermondsey Wing, Guy’s Hospital, London SE1 9RT, UK;Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

关键词: Albumin;    Calcium;    Gastrointestinal cancer;   

Others  :  1162019
DOI  :  10.1186/1471-2458-13-663

 received in 2012-12-21, accepted in 2013-05-19,  发布年份 2013

【 摘 要 】

Background

Observational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Meanwhile, limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study.

Methods

A cohort based on 492,044 subjects with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse associations between standardised levels, quartiles and age/sex-specific categories of serum calcium and risk of oesophageal, stomach, colon, rectal cancer and also colorectal cancer combined, while taking into account serum albumin and other comorbidities.

Results

During 12 years of follow-up, we identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon cancers, and 1495 rectal cancers. A positive association was found between albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 – 11.19) for high compared to normal age-specific calcium levels] and colon cancer [e.g. HR: 1.07 (95% CI: 1.00 – 1.14) for every SD increase of calcium] as well as colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of calcium] in women. In men there were similar but weaker non-statistically significant trends.

Conclusion

The positive relation between serum calcium, oesophageal cancer and colorectal cancer calls for further studies including calcium regulators to evaluate whether there is a true link between calcium metabolism and development of gastrointestinal cancer.

【 授权许可】

   
2013 Wulaningsih et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Lamprecht SA, Lipkin M: Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer 2003, 3(8):601-614. Research Support, U.S. Gov’t, P.H.S. Review
• [2]Yang K, Lamprecht SA, Shinozaki H, Fan K, Yang W, Newmark HL, et al.: Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and tumorigenesis in intestine of adenomatous polyposis coli1638N/+ mice. J Nutr 2008, 138(9):1658-1663. Research Support, N.I.H., Extramural
• [3]Cho E, Smith-Warner SA, Spiegelman D, Beeson WL, van den Brandt PA, Colditz GA, et al.: Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst 2004, 96(13):1015-1022. Meta-Analysis Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S
• [4]Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al.: Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006, 354(7):684-696.
• [5]Peacock M: Calcium metabolism in health and disease. Clin J Am Soc Nephrol 2010, 5(Suppl 1):S23-S30. Research Support, Non-U.S. Gov’t Review
• [6]Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G: Inflammatory markers, lipoprotein components and risk of major cardiovascular events in 65,005 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Atherosclerosis 2010, 213(1):299-305. Research Support, Non-U.S. Gov’t
• [7]Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR: Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the women’s health initiative limited access dataset and meta-analysis. BMJ 2011, 342:d2040. Meta-Analysis Research Support, Non-U.S. Gov’t Review
• [8]Jungner I, Marcovina SM, Walldius G, Holme I, Kolar W, Steiner E: Apolipoprotein B and a-I values in 147576 swedish males and females, standardized according to the world health organization-international federation of clinical chemistry first international reference materials. Clin Chem 1998, 44(8 Pt 1):1641-1649. Comparative Study Research Support, Non-U.S. Gov’t
• [9]Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E: High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 2001, 358(9298):2026-2033.
• [10]Holme I, Aastveit AH, Jungner I, Walldius G: Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med 2008, 264(1):30-38.
• [11]Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G: Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med 2009, 265(2):275-287. Research Support, Non-U.S. Gov’t
• [12]Walldius G, Jungner I, Kolar W, Holme I, Steiner E: High cholesterol and triglyceride values in Swedish males and females: increased risk of fatal myocardial infarction. First report from the AMORIS (Apolipoprotein related MOrtality RISk) study. Blood Press Suppl 1992, 4:35-42.
• [13]Van Hemelrijck M, Garmo H, Binda E, Hayday A, Karagiannis SN, Hammar N, et al.: Immunoglobulin E and cancer: a meta-analysis and a large Swedish cohort study. Cancer Causes Control 2010, 21:1657-1667.
• [14]Van Hemelrijck M, Garmo H, Holmberg L, Walldius G, Jungner I, Hammar N, et al.: Prostate cancer risk in the Swedish AMORIS study: the interplay between triglycerides, total cholesterol, and glucose. Cancer 2010. in press
• [15]Central Bureau for Statistics. Statistics Sweden. Stockholm, Sweden. 2008. Available from: http://www.scb.se/ webcite
• [16]Bringhurst F, Demay M, Krane S, Kronenberg H, et al.: Bone and mineral metabolism in health and disease. In Harrrion’s Prinicples of Internal Medicine. Edited by Fauci A, Longo D, Kasper D, Braunwald E, Jameson J, Loscalzo J. New York: McGraw-Hill; 2008.
• [17]Jungner I, Walldius G, Holme I, Kolar W, Steiner E: Apolipoprotein B and A-I in relation to serum cholesterol and triglycerides in 43,000 Swedish males and females. Int J Clin Lab Res 1992, 21(3):247-255.
• [18]Halthur C, Johansson AL, Almquist M, Malm J, Gronberg H, Manjer J, et al.: Serum calcium and the risk of prostate cancer. Cancer Causes Control 2009, 20(7):1205-1214.
• [19]Pintilie M: Competing risks : a practical perspective. Chichester, England. Hoboken, NJ: John Wiley & Sons; 2006.
• [20]Newmark HL, Yang K, Kurihara N, Fan K, Augenlicht LH, Lipkin M: Western-style diet-induced colonic tumors and their modulation by calcium and vitamin D in C57Bl/6 mice: a preclinical model for human sporadic colon cancer. Carcinogenesis 2009, 30(1):88-92. Research Support, N.I.H., Extramural
• [21]Newmark HL, Yang K, Lipkin M, Kopelovich L, Liu Y, Fan K, et al.: A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis 2001, 22(11):1871-1875. Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S
• [22]Jacobs ET, Jurutka PW, Martinez ME, Alberts DS: Vitamin D, calcium, and colorectal neoplasia: new insights on mechanisms of action. Cancer Prev Res (Phila) 2009, 2(3):197-199. Comment
• [23]Whitfield JF: Calcium, calcium-sensing receptor and colon cancer. Cancer Lett 2009, 275(1):9-16. Review
• [24]Cullen PJ, Lockyer PJ: Integration of calcium and Ras signalling. Nat Rev Mol Cell Biol 2002, 3(5):339-348. Research Support, Non-U.S. Gov’t Review
• [25]Whitfield JF: The calcium-sensing receptor--a driver of colon cell differentiation. Curr Pharm Biotechnol 2009, 10(3):311-316. Review
• [26]Wu K, Willett WC, Fuchs CS, Colditz GA, Giovannucci EL: Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst 2002, 94(6):437-446.
• [27]Mizoue T, Kimura Y, Toyomura K, Nagano J, Kono S, Mibu R, et al.: Calcium, dairy foods, vitamin D, and colorectal cancer risk: the fukuoka colorectal cancer study. Cancer Epidemiol Biomarkers Prev 2008, 17(10):2800-2807. Research Support, Non-U.S. Gov’t
• [28]Miller EA, Keku TO, Satia JA, Martin CF, Galanko JA, Sandler RS: Calcium, vitamin D, and apoptosis in the rectal epithelium. Cancer Epidemiol Biomarkers Prev 2005, 14(2):525-528. Research Support, U.S. Gov’t, P.H.S
• [29]Fedirko V, Bostick RM, Flanders WD, Long Q, Shaukat A, Rutherford RE, et al.: Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial. Cancer Prev Res (Phila) 2009, 2(3):213-223. Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t
• [30]Carroll C, Cooper K, Papaioannou D, Hind D, Pilgrim H, Tappenden P: Supplemental calcium in the chemoprevention of colorectal cancer: a systematic review and meta-analysis. Clin Ther 2010, 32(5):789-803. Meta-Analysis Research Support, Non-U.S. Gov’t Review
• [31]Mulholland HG, Murray LJ, Anderson LA, Cantwell MM: Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and its precursor conditions. Br J Nutr 2011, 106(5):732-741. Research Support, Non-U.S. Gov’t
• [32]Kuro-o M: Klotho in health and disease. Curr Opin Nephrol Hypertens 2012, 21:362-368.
• [33]Giovannucci E: Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. J Womens Health (Larchmt) 2003, 12(2):173-182. Review
• [34]Holzmann M, Jungner I, Walldius G, Ivert I, Nordqvist T, Ostergren J: Apolipoproteins B and A-I, standard lipid measures and incidence of myocardial infarction in men and women, with or without chronic kidney disease. Study IV in Thesis for doctorial degree (PhD). In Renal insufficiency, mortality and myocardial infarction. Edited by Holzmann M. Stockholm: Karolinska Institutet; 2008.