Breast Cancer far more likely in the sister having poor Vitamin D binding protein or poor CYP2R1 gene

Created March 2018

Genome-Wide Association Study of Serum 25-Hydroxyvitamin D in US Women.

Front Genet. 2018 Mar 1;9:67. doi: 10.3389/fgene.2018.00067. eCollection 2018.

O'Brien KM1, Sandler DP2, Shi M1, Harmon QE2, Taylor JA2, Weinberg CR1.

Study of genes of sisters with and without Breast Cancer 1. # Items in both categories Breast Cancer and Genetics are listed here: {category} --- This study does not contain the word RECEPTOR. The Vitamin D RECEPTOR is an important breast cancer gene 1. # Items in both categories Breast Cancer and Vitamin D Receptor are listed here: {category} --- 1. Genetics category listing contains the following {include}

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Genetic factors likely influence individuals' concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D exposure previously linked to reduced risk of several chronic diseases. We conducted a genome-wide association study of serum 25(OH)D (assessed using liquid chromatography-tandem mass spectrometry) and 386,449 single nucleotide polymorphisms (SNPs).

Our sample consisted of 1,829 participants randomly selected from the Sister Study, a cohort of women who had a sister with breast cancer but had never had breast cancer themselves. 19,741 SNPs were associated with 25(OH)D (p < 0.05). We re-assessed these hits in an independent sample of 1,534 participants who later developed breast cancer. After pooling, 32 SNPs had genome-wide significant associations (p < 5 × 10-8).

These were located in or near GC, the vitamin D binding protein, or CYP2R1, a cytochrome P450 enzyme that hydroxylates vitamin D to form 25(OH)D. The top hit was rs4588, a missense GC polymorphism associated with a 3.5 ng/mL decrease in 25(OH)D per copy of the minor allele (95% confidence interval [CI]: -4.1, -3.0; p = 4.5 × 10-38). The strongest SNP near CYP2R1 was rs12794714, a synonymous variant (p = 3.8 × 10-12; β = 1.8 ng/mL decrease in 25(OH)D per minor allele [CI: -2.2, -1.3]). Serum 25(OH)D concentrations from samples collected from some participants 3-10 years after baseline (811 cases, 780 non-cases) were also strongly associated with both loci. These findings augment our understanding of genetic influences on 25(OH)D and the possible role of vitamin D binding proteins and cytochrome P450 enzymes in determining measured levels. These results may help to identify individuals genetically predisposed to vitamin D insufficiency.

PMID: 29545823 PMCID: PMC5838824 DOI: 10.3389/fgene.2018.00067

Tags: Breast Cancer Genetics Vit D Binding Protein