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Abstract
Objective
Biological
markers that could aid in the detection of ovarian cancer are urgently
needed. Many ovarian cancers express parathyroid hormone-related
protein, which acts to raise calcium levels in serum. Thus, we
hypothesized that high serum calcium levels might predict ovarian
cancer.
Methods
We examined the
associations between total and ionized serum calcium and ovarian cancer
mortality in the Third National Health and Nutrition Survey (NHANES III)
using Cox proportional hazard models. We then examined the associations
of serum calcium with incident ovarian cancer in a second prospective
cohort, the NHANES Epidemiological Follow-up Study (NHEFS).
Results
There
were eleven deaths from ovarian cancer over 95,556 person-years of
follow-up in NHANES III. After multivariable adjustment, the risk for
fatal ovarian cancer was 52% higher for each 0.1 mmol/L increase in
total serum calcium (RH = 1.52, 95% CI 1.06–2.19) and 144% higher for
each 0.1 mmol/L increase in ionized serum calcium (RH = 2.44, 95%
CI = 1.45–4.09). Associations persisted after adjusting for nulliparity
and the use of oral contraceptives. Eight incident ovarian cancers
occurred over 31,089 person-years of follow-up in the NHEFS. After
adjusting for covariates, there was a 63% higher risk for ovarian cancer
with each 0.1 mmol/L increase in total serum calcium (95% CI
1.14–2.34). Similar results were observed for albumin-adjusted serum
calcium.
Conclusions
Higher
serum calcium may be a biomarker of ovarian cancer. This is the first
report of prospective positive associations between indices of calcium
in serum and ovarian cancer. Our findings require confirmation in other
cohorts.
Highlights
►
Two independent nationally representative population-based cohorts are
examined.
► Higher ionized and total serum calcium are associated with ovarian cancer mortality.
► Confirmation that higher total serum calcium is associated with incident ovarian cancer in a second cohort
► Higher ionized and total serum calcium are associated with ovarian cancer mortality.
► Confirmation that higher total serum calcium is associated with incident ovarian cancer in a second cohort
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