Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies.
To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I² test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations.
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. wahyu.wulaningsih@kcl.ac.uk.
Wahyu
W
Wulaningsih
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. harkiran.sagoo@kcl.ac.uk.
Harkiran K
HK
Sagoo
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. mustafa.hamza@kcl.ac.uk.
Mustafa
M
Hamza
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. jennifer.melvin@kcl.ac.uk.
Jennifer
J
Melvin
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. lars.holmberg@kcl.ac.uk.|Department of Surgical Sciences, Uppsala University Hospital, Uppsala 751 85, Sweden. lars.holmberg@kcl.ac.uk.|Regional Cancer Centre, Uppsala 751 83, Sweden. lars.holmberg@kcl.ac.uk.
Lars
L
Holmberg
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. hans.garmo@kcl.ac.uk.|Regional Cancer Centre, Uppsala 751 83, Sweden. hans.garmo@kcl.ac.uk.
Hans
H
Garmo
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. hakan.malmstrom@ki.se.
Håkan
H
Malmström
Regional Cancer Centre, Uppsala 751 83, Sweden. mats.lambe@ki.se.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden. mats.lambe@ki.se.
Mats
M
Lambe
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. niklas.hammar@ki.se.|AstraZeneca R&D, Mölndal 431 50, Sweden. niklas.hammar@ki.se.
Niklas
N
Hammar
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. goran.walldius@ki.se.
Göran
G
Walldius
Department of Medicine, Clinical Epidemiological Unit, Karolinska Institutet and CALAB Research, Stockholm 171 77, Sweden. ingmar.jungner@ki.se.
Ingmar
I
Jungner
Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London SE1 9RT, UK. mieke.vanhemelrijck@kcl.ac.uk.|Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. mieke.vanhemelrijck@kcl.ac.uk.
Mieke
M
Van Hemelrijck
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology; D002118:Calcium / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013548:Sweden
D014408:Biomarkers, Tumor; D002118:Calcium
albumin; breast cancer; calcium; prospective study