Vitamin D Receptor Gene Haplotypes and Polymorphisms and Risk of Breast Cancer: a Nested Case-control Study

Overview

Journal Cancer Epidemiol Biomarkers Prev

Specialties Biochemistry
Oncology
Public Health

Date 2012 Aug 16

PMID 22892281

Citations 21

Authors

Lawrence S Engel

Irene Orlow

Camelia S Sima

Jaya Satagopan

Urvi Mujumdar

Pampa Roy

Sarah Yoo

Dale P Sandler

Michael C Alavanja

Affiliations

Soon will be listed here.

Abstract

Background: Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitamin D are mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent.

Methods: We investigated VDR polymorphisms and haplotypes in relation to breast cancer risk by genotyping 26 single nucleotide polymorphisms (SNP) that (i) had known/suspected impact on VDR function, (ii) were tagging SNPs for the three VDR haplotype blocks among whites, or (iii) were previously associated with breast cancer risk. We estimated odds ratios (OR) and 95% confidence intervals (CI) in relation to breast cancer risk among 270 incident cases and 554 matched controls within the Agricultural Health Study cohort.

Results: In individual SNP analyses, homozygous carriers of the minor allele for rs2544038 had significantly increased breast cancer risk (OR = 1.5; 95% CI: 1.0-2.5) and homozygous carriers of the minor allele for rs11168287 had significantly decreased risk (OR = 0.6; 95% CI: 0.4-1.0). Carriers of the minor allele for rs2239181 exhibited marginally significant association with risk (OR = 1.4; 95% CI: 0.9-2.0). Haplotype analyses revealed three haplotype groups (blocks "A," "B," and "C"). Haplotype GTCATTTCCTA in block B was significantly associated with reduced risk (OR = 0.5; 95% CI: 0.3-0.9).

Conclusions: These results suggest that variation in VDR may be associated with breast cancer risk.

Impact: Our findings may help guide future research needed to define the role of vitamin D in breast cancer prevention.

Citing Articles

The Relationship between Gene Polymorphisms and with Breast Cancer Risk.

Mozaffarizadeh H, Mokarian F, Salehi M, Hakimian S, Moazam E, Amoozadehsamakoosh A Glob Med Genet. 2024; 11(1):69-75.

PMID: 38440355 PMC: 10911907. DOI: 10.1055/s-0044-1779040.

Assessment the effect of vitamin D supplementation on plasma vitamin D levels, inflammation, and oxidative stress biomarkers based on vitamin D receptor genetic variation in breast cancer survivors: a protocol for clinical trial.

Kazemian E, Akbari M, Moradi N, Gharibzadeh S, Amouzegar A, Rozek L J Health Popul Nutr. 2021; 40(1):46.

PMID: 34727991 PMC: 8561968. DOI: 10.1186/s41043-021-00272-9.

Vitamin D Receptor Genetic Variation and Cancer Biomarkers among Breast Cancer Patients Supplemented with Vitamin D3: A Single-Arm Non-Randomized Before and After Trial.

Kazemian E, Akbari M, Moradi N, Gharibzadeh S, Mondul A, Jamshidi-Naeini Y Nutrients. 2019; 11(6).

PMID: 31167402 PMC: 6628022. DOI: 10.3390/nu11061264.

Association of low penetrance vitamin D receptor Tru9I (rs757343) gene polymorphism with risk of premenopausal breast cancer.

Iqbal M, Maqbool S, Khan T J Int Med Res. 2018; 46(5):1801-1814.

PMID: 29529900 PMC: 5991241. DOI: 10.1177/0300060518761304.

Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway.

Amadori D, Serra P, Masalu N, Pangan A, Scarpi E, Bugingo A Oncotarget. 2017; 8(8):13142-13156.

PMID: 28061456 PMC: 5355083. DOI: 10.18632/oncotarget.14482.

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