Biomarkers for Risk of Breast Cancer During Pregnancy
A nested case control study
Acta Universitatis Tamperensis, No. 1585

By Bessem Calypse Agborsangaya
Febuary 2011
Tampere University Press
Distributed by Coronet Books Inc.
ISBN: 9789514483271
129 pages
$84.50 Paper Original

Breast cancer is a major public health problem, which is increasingly common in fertile-aged female populations, notably, also in conjunction with pregnancy (during pregnancy or one year post partum, i.e. the so called pregnancy associated breast cancer, PABC). Earlier findings indicate that breast cancer has a multi-factorial etiology, and biomarkers associated with cell differentiation and proliferation may act as potential indicators of the disease development. We assumed that prediagnostic serum vitamin D (25-dihydroxy vitamin D, 25-OHD) levels together with endogenous (steroid) hormone expression, exposure to Epstein-Barr virus (EBV), p53 expression might be potential indictors of the PABC risk. The validity and quality of the exposure/indicator measurements were confirmed by studying the effect of storage time on vitamin D and steroid hormones in serum samples stored for many years at -25 0C.

The present study utilised molecular epidemiological tools to evaluate the role of prediagnostic biomarkers (25-OHD, EBV and p53 serological markers as well as androstenedione) on the risk of development of breast cancer, with particular emphasis on PABC, one of more aggressive sub-groups of breast cancer.

Our case-control study was nested within the Finnish Maternity Cohort (FMC), a population-based biobank of first trimester serum samples. Eligible breast cancer cases consisted of two groups; women who developed breast cancer not more than ten years (but more than 20 months) from the date of sampling, and women with breast cancer diagnosis during pregnancy or one year after date of sample withdrawal. Age and pregnancy history matched controls were sampled within the same study population. The serum samples were analysed for 25-OHD as a measure of circulating vitamin D, immunoglobulin G (IgG) antibodies specific for EBV antigens Early Antigen (EA), EBV nuclear antigen (EBNA) and EBV replication activator, the ZEBRA protein. Levels of serum IgG antibodies specific to p53 and p53 protein were also studied.

We found that serum samples stored in the FMC biobank at -25 0C for up to 24 years does not affect 25-OHD detectability, and the samples can be used to study hormone and vitamin D-disease associations. However, it is important to match cases and controls for season of sample withdrawal in vitamin D related studies. No association was observed between vitamin D levels and risk of breast cancer in general. On the other hand, higher levels of vitamin D were associated with increased risk of breast cancer occurring during or soon after pregnancy. Previous EBV infection was not associated with increased risk of PABC, but serological EBV reactivation markers among individuals with more than sufficient levels of vitamin D were associated with a significantly increased risk of the disease. As for the association between prediagnostic serum p53 levels and PABC risk, we found that higher levels of p53 autoantibody were associated with a modest increased risk for development of PABC, which was significant among women with higher levels of vitamin D and androstenedione. This is the first study to provide direct epidemiological evidence on important biomarkers of the risk of PABC. The positive association between levels of vitamin D and risk of PABC remained significant among women with positive EBV reactivation. These observations are reminiscent of observations on other associations between EBV, vitamin D and chronic diseases, e.g. multiple schlerosis, but the underlying mechanisms remain not clear. Further studies are warranted to better understand the role and potential impact of circulating biomarkers on the risk of breast cancer occurring during or soon after pregnancy.

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