BsmI polymorphism of vitamin D receptor gene and cancer risk: A comprehensive meta-analysis

Research output: Contribution to journalArticle

Abstract

The VDR gene is an important regulator of the vitamin D pathway, and the role of some of its polymorphisms on cancer risk was previously investigated. A trend of cancer risk reduction with the VDR BsmI B allele was observed for many cancer sites. We performed a comprehensive meta-analysis to investigate the role of VDR BsmI polymorphism on cancer risk, even according to different ethnicities. Summary odds ratios (SORs) were calculated with random-effects models and maximum likelihood estimation. We categorized studies into three groups ("moderate", "high" and "very high confidence") according to departure from Hardy-Weinberg equilibrium in controls, reported minor allele frequency and genotyping quality controls. The meta-analysis included 73 studies with 45,218 cases and 52,057 controls. We found a significant 6-7% reduction of cancer risk at any site respectively for carriers of Bb genotype (SOR; 95%CI: 0.94; 0.90-0.99) and for carriers of BsmI BB genotype (SOR; 95%CI: 0.93; 0.89-0.98) compared to bb carriers, and they remain statistically significant when we restricted the analysis to at least "high confidence" studies. For skin cancer, a significant risk reduction was observed for Bb carriers (SOR; 95%CI: 0.86; 0.76-0.98). We also found a significant reduction of colorectal cancer risk for BB and Bb+. BB genotypes carriers, but these SORs were no more significant when we restricted the analysis to studies with "high confidence". When the analysis was stratified by ethnicity, we still observed a significant decreased risk for both Bb and BB compared to bb genotype among Caucasians: SORs (95%CI) for any cancer site were 0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups the inverse association was still present, but did not reach statistical significance. In conclusion, we suggest a weak effect of BsmI B allele in reducing cancer risk at any site, especially of the skin.

Original languageEnglish
Pages (from-to)17-34
Number of pages18
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume769
DOIs
Publication statusPublished - 2014

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Calcitriol Receptors
Neoplasm Genes
Meta-Analysis
Odds Ratio
Risk Reduction Behavior
Genotype
Neoplasms
Alleles
Skin Neoplasms
Ethnic Groups
Gene Frequency
Vitamin D
Quality Control
Colorectal Neoplasms
Skin
Genes

Keywords

  • BsmI
  • Meta-analysis
  • Molecular epidemiology
  • VDR
  • Vitamin D

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

@article{75281b73165f447c8b1bb7bdd0ff666c,
title = "BsmI polymorphism of vitamin D receptor gene and cancer risk: A comprehensive meta-analysis",
abstract = "The VDR gene is an important regulator of the vitamin D pathway, and the role of some of its polymorphisms on cancer risk was previously investigated. A trend of cancer risk reduction with the VDR BsmI B allele was observed for many cancer sites. We performed a comprehensive meta-analysis to investigate the role of VDR BsmI polymorphism on cancer risk, even according to different ethnicities. Summary odds ratios (SORs) were calculated with random-effects models and maximum likelihood estimation. We categorized studies into three groups ({"}moderate{"}, {"}high{"} and {"}very high confidence{"}) according to departure from Hardy-Weinberg equilibrium in controls, reported minor allele frequency and genotyping quality controls. The meta-analysis included 73 studies with 45,218 cases and 52,057 controls. We found a significant 6-7{\%} reduction of cancer risk at any site respectively for carriers of Bb genotype (SOR; 95{\%}CI: 0.94; 0.90-0.99) and for carriers of BsmI BB genotype (SOR; 95{\%}CI: 0.93; 0.89-0.98) compared to bb carriers, and they remain statistically significant when we restricted the analysis to at least {"}high confidence{"} studies. For skin cancer, a significant risk reduction was observed for Bb carriers (SOR; 95{\%}CI: 0.86; 0.76-0.98). We also found a significant reduction of colorectal cancer risk for BB and Bb+. BB genotypes carriers, but these SORs were no more significant when we restricted the analysis to studies with {"}high confidence{"}. When the analysis was stratified by ethnicity, we still observed a significant decreased risk for both Bb and BB compared to bb genotype among Caucasians: SORs (95{\%}CI) for any cancer site were 0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups the inverse association was still present, but did not reach statistical significance. In conclusion, we suggest a weak effect of BsmI B allele in reducing cancer risk at any site, especially of the skin.",
keywords = "BsmI, Meta-analysis, Molecular epidemiology, VDR, Vitamin D",
author = "Sara Raimondi and Elena Pasquali and Patrizia Gnagnarella and Davide Serrano and Davide Disalvatore and Johansson, {Harriet A.} and Sara Gandini",
year = "2014",
doi = "10.1016/j.mrfmmm.2014.06.001",
language = "English",
volume = "769",
pages = "17--34",
journal = "Mutation Research",
issn = "0027-5107",
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TY - JOUR

T1 - BsmI polymorphism of vitamin D receptor gene and cancer risk

T2 - A comprehensive meta-analysis

AU - Raimondi, Sara

AU - Pasquali, Elena

AU - Gnagnarella, Patrizia

AU - Serrano, Davide

AU - Disalvatore, Davide

AU - Johansson, Harriet A.

AU - Gandini, Sara

PY - 2014

Y1 - 2014

N2 - The VDR gene is an important regulator of the vitamin D pathway, and the role of some of its polymorphisms on cancer risk was previously investigated. A trend of cancer risk reduction with the VDR BsmI B allele was observed for many cancer sites. We performed a comprehensive meta-analysis to investigate the role of VDR BsmI polymorphism on cancer risk, even according to different ethnicities. Summary odds ratios (SORs) were calculated with random-effects models and maximum likelihood estimation. We categorized studies into three groups ("moderate", "high" and "very high confidence") according to departure from Hardy-Weinberg equilibrium in controls, reported minor allele frequency and genotyping quality controls. The meta-analysis included 73 studies with 45,218 cases and 52,057 controls. We found a significant 6-7% reduction of cancer risk at any site respectively for carriers of Bb genotype (SOR; 95%CI: 0.94; 0.90-0.99) and for carriers of BsmI BB genotype (SOR; 95%CI: 0.93; 0.89-0.98) compared to bb carriers, and they remain statistically significant when we restricted the analysis to at least "high confidence" studies. For skin cancer, a significant risk reduction was observed for Bb carriers (SOR; 95%CI: 0.86; 0.76-0.98). We also found a significant reduction of colorectal cancer risk for BB and Bb+. BB genotypes carriers, but these SORs were no more significant when we restricted the analysis to studies with "high confidence". When the analysis was stratified by ethnicity, we still observed a significant decreased risk for both Bb and BB compared to bb genotype among Caucasians: SORs (95%CI) for any cancer site were 0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups the inverse association was still present, but did not reach statistical significance. In conclusion, we suggest a weak effect of BsmI B allele in reducing cancer risk at any site, especially of the skin.

AB - The VDR gene is an important regulator of the vitamin D pathway, and the role of some of its polymorphisms on cancer risk was previously investigated. A trend of cancer risk reduction with the VDR BsmI B allele was observed for many cancer sites. We performed a comprehensive meta-analysis to investigate the role of VDR BsmI polymorphism on cancer risk, even according to different ethnicities. Summary odds ratios (SORs) were calculated with random-effects models and maximum likelihood estimation. We categorized studies into three groups ("moderate", "high" and "very high confidence") according to departure from Hardy-Weinberg equilibrium in controls, reported minor allele frequency and genotyping quality controls. The meta-analysis included 73 studies with 45,218 cases and 52,057 controls. We found a significant 6-7% reduction of cancer risk at any site respectively for carriers of Bb genotype (SOR; 95%CI: 0.94; 0.90-0.99) and for carriers of BsmI BB genotype (SOR; 95%CI: 0.93; 0.89-0.98) compared to bb carriers, and they remain statistically significant when we restricted the analysis to at least "high confidence" studies. For skin cancer, a significant risk reduction was observed for Bb carriers (SOR; 95%CI: 0.86; 0.76-0.98). We also found a significant reduction of colorectal cancer risk for BB and Bb+. BB genotypes carriers, but these SORs were no more significant when we restricted the analysis to studies with "high confidence". When the analysis was stratified by ethnicity, we still observed a significant decreased risk for both Bb and BB compared to bb genotype among Caucasians: SORs (95%CI) for any cancer site were 0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups the inverse association was still present, but did not reach statistical significance. In conclusion, we suggest a weak effect of BsmI B allele in reducing cancer risk at any site, especially of the skin.

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KW - Molecular epidemiology

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KW - Vitamin D

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