The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population

Molecular Oncology Unit and Department of Urology, Laboratórios-PISO 4, Instituto Português de Oncologia, R. Dr. Ant. Bernardino Almeida 4200-072 Porto, Portugal.
Journal of Human Genetics (Impact Factor: 2.53). 02/2002; 47(8):413-8. DOI: 10.1007/s100380200060
Source: PubMed

ABSTRACT Epidemiological data indicate a relationship between ultraviolet radiation, vitamin D, and prostate cancer risk. Antiproliferative effects of vitamin D require the expression of the nuclear vitamin D receptor (VDR). A three-fold increase in prostate cancer risk associated with the less active vitamin D receptor allele (the T allele from VDR TaqI polymorphism at codon 352) was reported. The role of VDR genotypes in the susceptibility to prostate cancer has not yet been studied in populations of southern Europe. In the present study, we determined VDR TaqI genotypes in Portuguese prostate cancer cases ( n = 163) and controls ( n = 211), a southern European population. When cases were compared with controls, we found an association of VDR T allele with prostate cancer risk (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02-3.37; P = 0.035). This association was confirmed using logistic regression analysis (OR = 2.11, 95% CI 1.15-3.88; P = 0.015) and in particular associated to risk of prostate cancer onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05-5.29; P = 0.036). Fifty percent of cases older than 66 years could be attributed to the influence of this risk factor. Our results indicate that the contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization, and that VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe.

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Available from: Rui Medeiros, Jul 22, 2015
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    • "Although some studies detected no association detected between VDR polymorphisms and prostate cancer risk, more studies have shown a positive association in different populations including Caucasian American, African American, Chinese, Japanese, European, and Indian [Medeiros et al., 2002]. Carriers of less-active VDR alleles usually have an increased risk of prostate cancer. "
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    ABSTRACT: Quantitative and structural genetic alterations cause the development and progression of prostate cancer. A number of genes have been implicated in prostate cancer by genetic alterations and functional consequences of the genetic alterations. These include the ELAC2 (HPC2), MSR1, and RNASEL (HPC1) genes that have germline mutations in familial prostate cancer; AR, ATBF1, EPHB2 (ERK), KLF6, mitochondria DNA, p53, PTEN, and RAS that have somatic mutations in sporadic prostate cancer; AR, BRCA1, BRCA2, CHEK2 (RAD53), CYP17, CYP1B1, CYP3A4, GSTM1, GSTP1, GSTT1, PON1, SRD5A2, and VDR that have germline genetic variants associated with either hereditary and/or sporadic prostate cancer; and ANXA7 (ANX7), KLF5, NKX3-1 (NKX3.1), CDKN1B (p27), and MYC that have genomic copy number changes affecting gene function. More genes relevant to prostate cancer remain to be identified in each of these gene groups. For the genes that have been identified, most need additional genetic, functional, and/or biochemical examination. Identification and characterization of these genes will be a key step for improving the detection and treatment of prostate cancer.
    Journal of Cellular Biochemistry 02/2006; 97(3):433-47. DOI:10.1002/jcb.20696 · 3.37 Impact Factor
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    • "The odds ratio (OR) and its 95% confidence interval (CI) were calculated as a measure of the association between ACE genotypes and endometrial cancer risk. We calculated the attributable proportion by the following formula: AP ϭ PRF × (1Ϫ1/OR) as previously reported [23] "
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    ABSTRACT: Endometrial carcinoma is one of the most common gynecological malignancies. Most cases are diagnosed in older patients with diabetes, hypertension, or obesity. The renin-angiotensin system (RAS) has a central role controlling blood pressure and sodium homeostasis. RAS polymorphisms have been reported as genetic determinants of essential hypertension. The objective of this study was to analyze angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. The presence of an angiotensin converting enzyme (ACE) polymorphism was analyzed by polymerase chain reaction in DNA isolated from peripheral blood samples of 171 women: 70 cases with endometrial cancer (age, 63.6 +/- 9.5 years) and 101 normal control women (age, 61.3 +/- 6.4 years). We detected DD genotype in 47.5%, ID genotype in 44.3%, and II genotype in 8.2% of cases. The allele frequency was 0.69 for D allele and 0.30 for I allele. In normotensives, we found that the presence of I allele (genotypes ID and II) is significantly associated to an earlier age (56.0 +/- 10.1 versus 65.8 +/- 9.9) of onset of endometrial carcinoma (P=0.029). We observed that normotensive women carriers of an allele I have a higher risk of development of endometrial cancer under the age of 63 years (odds ratio=3.60, 95% confidence interval=1.03-12.56; P=0.037). Our findings suggest that ACE polymorphism may be associated with the development of endometrial carcinoma and with the onset of this tumor in younger women. The definition of a pharmacogenomic profile of human neoplasia may help to identify targets for the development of therapeutic or chemoprevention strategies.
    Cancer Genetics and Cytogenetics 12/2004; 155(1):42-6. DOI:10.1016/j.cancergencyto.2004.03.020 · 1.93 Impact Factor
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    • "Since 1996, there have been many reports of associations of polymorphisms of the VDR with systemic carcinomas. The 3 0 polymorphisms have been reported to be associated with the occurrence and outcome, as assessed by metastasis or presence of adverse prognostic markers, of prostatic cancer (Taylor et al, 1996; Ingles et al, 1997c; Ingles et al, 1998; Ma et al, 1998; Habuchi et al, 2000; Hamasaki et al, 2001; Medeiros et al, 2002), breast cancer (Curran et al, 1999; Lundin et al, 1999; Ingles et al, 2000; Bretherton-Watt et al, 2001; Cui et al, 2001; Schondorf et al, 2003) and renal cancer (Ikuyama et al, 2002). Fok 1 polymorphisms have been reported to be associated with the outcome of prostate cancer (Hamasaki et al, 2002) and occurrence of breast (Ingles et al, 1997a) and colon (Wong et al, 2003) cancers. "
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    ABSTRACT: The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as predicted by tumour (Breslow) thickness, has been reported previously. We now report a novel adenine-guanine substitution -1012 bp relative to the exon 1a transcription start site (A-1012G), found following screening by single-stranded conformational polymorphism of this promoter region. There was a total of 191 MM cases, which were stratified according to conventional Breslow thickness groups, cases being randomly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area, and this population (n=176) was compared to 80 controls. The A allele was over-represented in MM patients and, with GG as reference, odds ratio (OR) for AG was 2.5, 95% confidence interval (CI) 1.1-5.7, (P=0.03) and AA 3.3, CI 1.4-8.1, (P=0.007). The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis, the Kaplan-Meier estimates of the probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4-16%; AA 21%, CI 12-36%; (P=0.008), and to thicker Breslow thickness groups (P=0.04). The effect on metastasis was independent of tumour thickness and A-1012G may have predictive potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants (f and t) were significantly related to the development of metastasis, although there was a strong relationship of fftt with the thickest Breslow thickness group (P=0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms (P=0.025) and the Fok 1 variant enhanced the effect of the A allele of the A-1012G polymorphism on metastasis, the probability of metastasis for AAff at 5 years follow-up being 57%, CI 24-92%.
    British Journal of Cancer 09/2004; 91(4):765-70. DOI:10.1038/sj.bjc.6602006 · 4.82 Impact Factor
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