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.
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Electronic address: sara.raimondi@ieo.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pasquali
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gnagnarella
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Disalvatore
authors.affiliation: Division of Cancer Prevention and Genetics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Harriet A
authors.initials: HA
authors.lastname: Johansson
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
mesh_terms: D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005006:Ethnicity / Q000235:genetics / Q000706:statistics & numerical data; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific
keywords: BsmI; Meta-analysis; Molecular epidemiology; VDR; Vitamin D