SNPs related to vitamin D and breast cancer risk: a case-control study

• Published in: Breast cancer research : BCR Vol. 20; no. 1; pp. 1 - 13
• Main Authors: Huss, Linnea, Butt, Salma Tunå, Almgren, Peter, Borgquist, Signe, Brandt, Jasmine, Försti, Asta, Melander, Olle, Manjer, Jonas
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.01.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer and Oncology; Cancer och onkologi; Clinical Medicine; Cohort Studies; Female; Gene Frequency; Genetic aspects; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Health aspects; Humans; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Polymorphism; Polymorphism, Single Nucleotide - genetics; Risk Factors; Single nucleotide polymorphisms; SNP; Vitamin D; Vitamin D - blood; Vitamin D - genetics; Breast cancer; SNP; Vitamin D; Polymorphism
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-017-0925-3

It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels. The Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer. The majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68-0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52-1.00). Results from stratified analyses showed diverse associations with breast cancer risk for a few of the tested SNPs, depending on whether vitamin D level was high or low. SNPs associated with vitamin D may also be associated with the risk of breast cancer. Even if such a risk is small, the allele frequency of the SNP variants is high, and therefore the population attributable risk could be substantial. It is also possible that vitamin D levels may interact with genomic traits with regard to breast cancer risk.