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

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Huss L

PROVIDER: S-EPMC5748964 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Huss Linnea L Butt Salma Tunå ST Almgren Peter P Borgquist Signe S Brandt Jasmine J Försti Asta A Melander Olle O Manjer Jonas J

Breast cancer research : BCR 20180102 1

<h4>Background</h4>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 deter ...[more]

PMID: 29291743

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Project description:BackgroundEMSY could be involved in low-level susceptibility to breast and ovarian cancer. Gene amplification is seen in a proportion of breast and ovarian tumours and correlates with poor prognosis in breast cancer patients. Furthermore, the EMSY protein silences a transcription activation domain in BRCA2 exon 3.MethodsWe used a genetic association study design to determine if common genetic variation (frequency > or = 5%) in EMSY was associated with breast or ovarian cancer risk in the British population. Haplotype tagging single-nucleotide polymorphisms (htSNPs) were selected from the HapMap database and genotyped using Taqman in two large study sets of white British women (n [breast set] = 2343 cases and 2284 controls, n [ovarian set] = 864 cases and 864 controls). HapMap data might be insufficient to tag genetic variation in EMSY comprehensively. We therefore screened the gene promoter and coding sequences with denaturing high performance liquid chromatography in order to identify additional SNPs that are most likely to be functional.ResultsHapMap data on 22 SNPs show that 4 htSNPs tag 4 common haplotypes: rs2282611 (5'up t > g), rs4245443 (IVS7 g > a), rs2513511 (IVS16 a > g), rs2155220 (3'down c > t). We observed no association between any of the genotypes or associated haplotypes and breast or ovarian cancer risk. Seventeen out of the 18 remaining HapMap polymorphisms (94%) were well tagged by the 4 selected htSNPs (r2s > 0.8). Genotype frequencies for two further SNPs identified by screening and located near exon-intron boundaries, rs2508740 (IVS9 a > g) and rs11600501 (IVS10 c > t), were also similar in cases and controls. In order to simulate unidentified SNPs, we performed the leave-one-out cross-validation procedure on the HapMap data; over 95% of the common genetic variation was well represented by tagging polymorphisms. We are therefore likely to have tagged any common, functional variants present in our population.ConclusionWe found no association between common genetic variation in EMSY and risk of breast or ovarian cancer in two large study sets of white British women.

Project description:Breast cancer is the most prevalent cancer in females worldwide. Studies evaluating the blood vitamins and minerals status in the breast cancer etiology are limited, and the results are inconclusive. This study analyzed the association between serum vitamin-mineral profiles (V-MPs) and breast cancer (BC) risk with including dietary patterns (DPs) and the use of supplements. This case-control study involved 420 women aged 40-79 years from north-eastern Poland, including 190 newly diagnosed breast cancer cases. The fasting serum concentrations of vitamins (folate, cobalamin, 25(OH) vitamin D) and minerals (iron, calcium, magnesium) were measured in 129 post-menopausal women, including 82 controls and 47 cases. Three V-MPs were derived with a Principal Component Analysis (PCA). A logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of the breast cancer risk associated with serum V-MPs and serum levels of single biomarkers. The risk of BC was lower by 88% (OR: 0.12; 95% Cl: 0.02-0.88; p < 0.05) in the upper tertile of the serum 'Iron-Calcium' profile compared to the bottom tertile, lower by 67% (OR: 0.33; 95% Cl: 0.11-0.97; p < 0.05) at the level of serum 25(OH) vitamin D ?24.6 ng/mL and lower by 68% (OR: 0.32; 95% Cl: 0.11-0.91; p < 0.05) at the level of serum calcium ?9.6 mg/dL. There was an inverse association of the serum 'Magnesium' profile or serum level of iron with the risk of BC, which disappeared after adjustment for the set of confounders accounted for: age, body mass index (BMI), socioeconomic status, overall physical activity, smoking status, age at menarche, number of full-term pregnancies, oral contraceptive use, hormone-replacement therapy use, family history of breast cancer, vitamin/mineral supplement use, the molecular subtype of breast cancer, and dietary patterns. No significant association was found between BC risk and the serum 'Folate-Cobalamin-Vitamin D' profile or serum folate, cobalamin or magnesium considered separately. These findings highlight that a higher-normal serum level of both iron and calcium, considered together as the serum profile, as well as a higher-normal serum level of calcium, considered separately, and a slightly below the normal range of serum vitamin D level may protect against breast cancer among postmenopausal women, independent of dietary patterns or the use of vitamin/mineral supplements. Therefore, the maintenance of the adequate status of vitamins and minerals and the regular monitoring of their blood markers should be included in breast cancer prevention.

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

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

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