Medeiros R, Morais A, Vasconcelos A, Costa S, Pinto D, Oliveira J, Lopes CThe role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population. J Hum Genet 47: 413-418

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: 2.46). 02/2002; 47(8):413-8. DOI: 10.1007/s100380200060
Source: PubMed


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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    • "SNPs rs731236 and other flag material in this chromosomal region are stronly unbalanced; thus it is considered that this SNPs is strongly related to PCa occurance [22]. Medeiros [23] confirmed that in the VDR Taq I genes, rs731236 polymorphism, people who carry allele C homozygotes only have 1/3 (OR = 0.34, 95% CI, 0.16 ~ 0.76, P <0.01) of the risk to have PCa compared with those who carry miscellaneous zygote or T homozygous, therefore CC homozygotes gene is thought to prevent individual from suffering from PCa. However Gsur et al. [24] confirmed that within the Caucasian population in Austria, the VDR Taq I gene polymorphism is not related to the risk of suffering from PCa; the frequencies of the CC genotype in PCa patients and the corresponding controls, are 18% and 12%, respectively, and difference is not statistically significant (OR = 1.76, 95% CI, 0.90 to 3.45, P = 0 07). Our study confirms that within the Chinese Han population, the appearing frequencies of the genotype TT, TC, and CC in the SNPs, rs731236 (T/C) VDR of PCa patients and the control group are 88.89%, 9.26%, 1.85% and 90.50%, 9.10%, 0.40%, (P = 0.643), and correlation is found between rs731236 and the occurrence PCa. "
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    ABSTRACT: To investigate the relationship and interaction of the single nucleotide polymorphisms(SNPs) of KLK3 and VDR and environmental factors with the predisposition to prostate cancer within Chinese population. The comparison between 108 patients and 242 healthy people was carried out by using the TaqMan/MGB Probe Technology to determine the genotypes of KLK3(rs2735839 is located between KLK2 and KLK3) and VDR (rs731236 is located exon 9). Univariate and multivariate logistic regression model were used to assess the connection of genetic polymorphisms and environmental risk factors with PCa by collecting demographic information, as well as BMI, consumption of cigarettes, alcohol, and tea, exercise, and other environmental risk factors. The appearing frequencies of AA, AG, and GG genotypes at the SNPs rs2735839 (A/G) for KLK3 were 13.89%, 62.96% and 23.15% in PCa and 37.19%, 44.63%, 18.18% in control, respectively; these two groups are statistically different (P = 0.00). While the appearing frequencies of TT, TC, and CC genotypes at the SNPs rs731236 (T/C) for VDR were 88.89%, 9, 26%, 1.85% and 90.50%, 9.10%, 0.40% in control, respectively, with no significant statistical difference between the two group. The study confirmed decreasing risk in tea drinkers(OR = 0.58, 95%CI = 0.35-0.96). Our studies indicate that environmental factor-tea drinking is associated with the development of PCa. The habit of drinking tea is a protective factor against PCa. The SNPs rs2735839 for KLK3 is strongly related to the development of PCa, while the SNPs rs731236 for VDR is not.Virtual slides: The virtual slide(s) for this article can be found here: Slides: The virtual slide(s) for this article can be found here:
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    • "In conclusion, over the past 10 years, our group has been studying the role of genetic polymorphism in cancer development (48–54). This is the first study to evaluate the role of the ATM D1853N (5557G>A) and p53bp1 D353E (1236C>G) polymorphisms in the development of cervical cancer in Portugal. "
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    ABSTRACT: Persistent infections by high-risk types of human papillomavirus (HPV) have been established as the etiological agent of cervical cancer. The integration of the HPV genome into the host genome is a crucial step in cervical carcinogenesis, although, correct activation of DNA damage repair pathways will avoid the development of cancer. Recent data indicate that several polymorphisms of key regulators from the DNA damage repair pathway (i.e. 53BP1 and ATM) are associated with cancer development susceptibility. We have developed a hospital-based retrospective study considering 429 cervical specimens from women with different cervical lesions including invasive carcinoma. This study aimed to evaluate the role of the ATM D1853N (5557G>A) and 53bp1 D353E (1236C>G) polymorphisms in the development of cervical cancer, using TaqMan SNP Genotyping Assays. Statistical analysis revealed that ATM 5557GG homozygous individuals (OR=1.94; p=0.044) are at increased risk of developing LSIL, while for the 53BP1 1236C>G polymorphism no association was found. Nevertheless, we observed a tendency for an increased risk of LSIL in 53BP1 1236C allele carriers (OR=1.63; p=0.069). Logistic regression adjusted for age revealed no significant differences from the non-adjusted analysis. This is the first study to evaluate the role of ATM G5557A and P53BP1 C1236G polymorphisms in cervical cancer susceptibility. This study reveals a possible trend of both polymorphisms for a genetic susceptibility pattern of cervical cancer development. Hence, our results may be of interest for future understanding of the progression of cervical cancer.
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    • "However, other studies [29-33] did not show such significant associations. The inconsistent results were probably due to differences in the study populations [20,22]. "
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    ABSTRACT: Molecular epidemiological studies have shown that gene polymorphisms of vitamin D receptor (VDR) are associated with prostate cancer risks. However, previous results from many molecular studies remain inconsistent. Blood samples were collected from 122 prostate cancer patients and 130 age-matched control subjects in the Han population of Southern China. The differences of VDR gene polymorphism between cancer cases and controls were determined by PCR-RFLP, examiming FokI (exon 2), BsmI, Tru9I, ApaI (intron 9), and TaqI (exon 9). Associations between the VDR gene polymorphism and prostate cancer risk were calculated in an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. Of five polymorphisms, BsmI was shown to associate with prostate cancer, while FokI, Tru9I, ApaI, and TaqI did not show any significant association. After adjustment for age, the BsmI 'B' allele was associated with an almost 1/3-fold risk (OR = 0.35, 95%CI: 0.15-0.80) of the occurrence of prostate cancer, a 1/5-fold risk (OR = 0.20, 95%CI: 0.06-0.68) of poorly differentiated prostate cancer, and a 1/10-fold risk (OR = 0.10, 95%CI: 0.01-0.78) of aggressive prostate cancer compared with the 'b' allele, especially among older men (>71 years). In addition, haplotype analysis revealed that the 'F-b-U-A-T' was more frequent found in cases than in controls (3.4% vs 0.0%, P = 0.0035), while the frequency of haplotype 'F-B-U-a-T' was 0.8% in cases, significantly lower than in controls (3.9%, P = 0.019). Our experiments provide evidences that genetic polymorphisms in the VDR gene may be potential risk factors for prostate cancer in the Han population of southern China and the susceptibility to prostate cancer is associated with ethnicity and geographic location.
    Full-text · Article · Dec 2009 · BMC Medical Genetics
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