Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study

Abstract

Previous studies indicate that calcium and its regulating hormones, i.e., parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD(3), PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD(3), and the OR for the 2nd, 3rd and 4th quartiles, as compared to the first, were 0.84 (0.60-1.15), 0.84 (0.60-1.17) and 0.93 (0.66-1.33). Serum calcium was positively associated with breast cancer in premenopausal women (OR for the 4th quartile = 3.10:1.33-7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th quartile = 1.94:1.12-3.37 and p for trend < 0.01). There was no association between baseline serum PTH and breast cancer risk.

Plasma 25‐hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: A nested case–control study

“…21 Although this result is obviously consistent with ours, underlying mechanisms remain to be identified. As no effect modification by BMI was observed in several other prospective studies 23,[29][30][31]33 and case-control studies, 27,34 the differential association depending on BMI observed in our study may also be due to chance and requires further exploration. Heterogeneity in the association between circulating 25(OH)D and breast cancer risk was also detected across strata of HRT use at blood donation.…”

“…First, a crude model was built accounting for matching variables only, i.e., study center, age, menopausal status, exogenous hormone use, time of the day of blood collection, fasting status and phase of the menstrual cycle. Second, a multivariable model was built adjusting for potential confounders, i.e., body mass index (BMI, <25, 25-29.9 and 30 kg=m 2 ), age at first menses (<7 or missing, 7-10, 11-13 and 13 years), number of full-term pregnancies (1, 2, 3 and nulliparous), age at first full-term pregnancy (20,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and >30 years), breastfeeding (yes or no), alcohol consumption (<1.5, 1.5-9.9, 10-19.9, 20-29.9 and 30 g=day), smoking status (never, former and current), education level (none or primary school completed, technical or professional school, secondary school and longer education including university degree) and physical activity according to the Cambridge Physical Activity Index (inactive, moderately inactive, moderately active and active). A category for missing values was created for all adjustment variables.…”

“…21,30,31 Finally, there was no indication for heterogeneity across seasons of blood draw with respect to 25(OH)D and breast cancer risk in our study and other studies. 21,23,30,31 Contradictory findings from case-control and prospective studies on vitamin D and breast cancer risk have been attributed to possible lifestyle changes of cancer patients affecting 25(OH)D levels. 15,18 The average follow-up time of 4.1 years between blood donation and diagnosis in our study makes it unlikely that 25(OH)D levels were influenced by lifestyle modifications due to cancer.…”

“…As 25(OH)D in relation to breast cancer risk had been assessed before the start of our project in the Malm€ o Diet and Cancer Study, which is part of EPIC, 23 participants from Malm€ o were not included. In contrast, the case set for our study does include 160 incident cases from the French E3N cohort.…”

In Serum, Higher Parathyroid Hormone but Not Lower Vitamin D Is Associated with Oral Squamous Cell Carcinoma

“…The pth receptor is expressed in keratinocytes 29,30 , and a positive association between the risk of breast cancer and primary hyperparathyroidism has also been reported 31 . However, one study also showed no association between baseline serum pth and breast cancer risk 32 .…”