UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR = 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis.
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PMID:Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene. 1243 3

Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.
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PMID:Polymorphisms in DNA repair genes and associations with cancer risk. 1249 39

Together with cell cycle checkpoint control, DNA repair plays a pivotal role in protecting the genome from endogenous and exogenous DNA damage. Although increased genetic instability has been associated with prostate cancer progression, the relative role of DNA double-strand break repair in malignant versus normal prostate epithelial cells is not known. In this study, we determined the RNA and protein expression of a series of DNA double-strand break repair genes in both normal (PrEC-epithelial and PrSC-stromal) and malignant (LNCaP, DU-145, and PC-3) prostate cultures. Expression of genes downstream of ATM after ionizing radiation-induced DNA damage reflected the p53 status of the cell lines. In the malignant prostate cell lines, mRNA and protein levels of the Rad51, Xrcc3, Rad52, and Rad54 genes involved in homologous recombination were elevated approximately 2- to 5-fold in comparison to normal PrEC cells. The XRCC1, DNA polymerase-beta and -delta proteins were also elevated. There were no consistent differences in gene expression relating to the nonhomologous end-joining pathway. Despite increased expression of DNA repair genes, malignant prostate cancer cells had defective repair of DNA breaks, alkali-labile sites, and oxidative base damage. Furthermore, after ionizing radiation and mitomycin C treatment, chromosomal aberration assays confirmed that malignant prostate cells had defective DNA repair. This discordance between expression and function of DNA repair genes in malignant prostate cancer cells supports the hypothesis that prostate tumor progression may reflect aberrant DNA repair. Our findings support the development of novel treatment strategies designed to reinstate normal DNA repair in prostate cancer cells.
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PMID:Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression. 1557 58

As part of a population-based case-control study in Shanghai, China, we investigated whether variants in several DNA repair genes, either alone or in conjunction with other risk factors, are associated with prostate cancer risk. Genomic DNA from 162 patients newly diagnosed with prostate cancer and 251 healthy men randomly selected from the population were typed for five nonsynonymous DNA repair markers. We found that the XRCC1-Arg399Gln AA and the MGMT-Leu84Phe CT+TT genotypes were associated with an increased risk of prostate cancer [odds ratio (OR), 2.18; 95% confidence interval (CI), 0.99-4.81 and OR, 1.99; 95% CI, 1.19-3.34, respectively]. In contrast, XRCC3-Thr241Met, XPD-Lys751Gln, and MGMT-Ile143Val markers showed no significant associations with risk, although due to the much lower frequency of their variant alleles in this population we cannot rule out small to modest effects. There was a significant interaction between the MGMT-84 marker and insulin resistance (P(interaction) = 0.046). Relative to men with the MGMT-84 CC genotype and a low insulin resistance (<0.097), those having the CT-TT genotype and a greater insulin resistance had a 5.4-fold risk (OR, 5.39; 95% CI, 2.46-11.82). In addition, for the XRCC3-241 marker, relative to men with the CC genotype and a low intake of preserved foods (<12.7 g/d), those harboring the CT+TT genotype and having a higher intake of preserved foods (>12.7 g/d), which contain nitrosamines and nitrosamine precursors, had a significantly increased risk of prostate cancer risk (OR, 2.62; 95% CI, 1.13-6.06). In contrast, men with the CT+TT genotype and a low intake of preserved foods had a 69% reduction in risk (OR, 0.31; 95% CI, 0.10-0.96; P(interaction) = 0.005). These results suggest that genetic variants in the DNA repair pathways may be involved in prostate cancer etiology and that other risk factors, including preserved foods and insulin resistance, may modulate prostate cancer risk in combination with genetic susceptibility in these repair pathways. Replication in larger studies is necessary to preclude chance findings, particularly those among subgroups, and clarify the mechanisms involved.
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PMID:Genetic variants of DNA repair genes and prostate cancer: a population-based study. 1603 Jan 5

Increasing evidence supports the important role of nutrition in cancer prevention, including prevention of prostate cancer. In this review, we summarize data for some of the most consistently observed dietary associations for prostate cancer incidence, briefly consider possible postdiagnostic effects of nutrition on prostate cancer progression/survival, discuss new but limited data on diet-gene interactions, and comment on current areas of controversy for future research focus. Potential protective dietary elements include tomatoes/lycopene, other carotenoids, cruciferous vegetables, vitamin E, selenium, fish/marine omega-3 fatty acids, soy, isoflavones and polyphenols; whereas milk, dairy, calcium, zinc at high doses, saturated fat, grilled meats, and heterocyclic amines may increase risk. It is important to note that randomized clinical trial data exist only for vitamin E, calcium, beta-carotene, and selenium (all of which suggest inverse or no association). Several genes, such as MnSOD, XRCC1, and GST, may modify the association of specific nutrients and foods with prostate cancer risk; and further research is warranted to confirm these initial observed relationships. Until further clinical trial data are available on specific supplements and prostate cancer prevention, it would be prudent to emphasize a diet consisting of a wide variety of plant-based foods and fish; this is similar to what is recommended (and what is more well established) for the primary prevention of heart disease.
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PMID:Role of diet in prostate cancer development and progression. 1627 66

To date, the potential impact of hormones on prostate cancer has predominantly focused on receptor-mediated events. However, catechol estrogens, if not inactivated by catechol-O-methyltransferase (COMT), can generate large quantities of reactive oxygen species (ROS). ROS may cause a spectrum of damage including oxidative DNA base lesions, which can lead to irreversible mutation(s) if they are not repaired by base excision repair (BER) systems. hOGG1 is a key enzyme in short patch BER because it recognizes and performs initial excision of the most common form of oxidative DNA base damage, 8-hydroxyguanine (8-oxo-dG). To investigate potential non-receptor-mediated estrogen effects, we evaluated the association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate cancer in a family-based case-control study (439 prostate cancer cases, 479 brother controls). We observed no noteworthy associations between these polymorphisms and prostate cancer risk in the total study population. However, among men with more aggressive prostate cancer, the hOGG1 326 Cys/Cys genotype was inversely associated with disease (OR=0.30; 95% CI=0.09-0.98). Combining the lower activity CYP1B1 432 Leu/Leu or Leu/Val genotypes (which may decrease the level of catechol estrogens and ROS generated) with the hOGG1 326 Cys/Cys genotype and the XRCC1 399 Arg/Arg or Arg/Gln genotypes (which may enhance BER) resulted in an even further reduced risk in Caucasians with more aggressive disease (OR=0.09; 95% CI=0.01-0.56). Including the high-activity COMT 158Val allele to this combination also lowered aggressive prostate cancer risk but the effect was not as strong (OR=0.20; 95% CI=0.05-0.88). The decreased risk we observed with the hOGG1 326 Cys/Cys genotype confirms an earlier report and the further reduced risk found with the CYP1B1 (432 Leu/Leu or Leu/Val)-hOGG1 (326 Cys/Cys)-XRCC1 (Arg/Arg or Arg/Gln) genotype combination may lend new insights to the importance of ROS generated from non-receptor-mediated estrogenic mechanisms in more aggressive prostate cancer.
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PMID:Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base excision repair genes and prostate cancer risk. 1656 55

Lycopene has been associated with reduced prostate cancer risk, although the results of epidemiological studies have varied. We hypothesize that an effect of lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food-frequency questionnaire to assess lycopene intake in a case-control study of prostate cancer in North Carolina. Plasma alpha-tocopherol and beta-carotene levels were measured using high-performance liquid chromatography. XRCC1 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism. The final dataset included 77 cases and 174 controls with complete questionnaires, genotyping, and plasma analyses. Among men with the Arg/Arg genotype at codon 399, odds ratios (ORs) for prostate cancer risk associated with medium (732-1,529 microg/day) and high (>1,529 microg/day) lycopene intake were 0.59 (95% confidence interval = 0.23-1.50) and 0.21 (0.06-0.71), respectively (P(trend) < 0.01). Similar analyses for persons with Arg/Gln or Gln/Gln genotypes produced null results. Above-median (1,048 microg/day) lycopene intake combined with above-median levels of alpha-tocopherol and beta-carotene was associated with an OR of 0.11 (0.02-0.65) among men with the Arg/Arg genotype but not those with at least one Gln allele (P(interaction) = 0.01). Although limited by small sample size, these findings indicate that the association between lycopene and prostate cancer is complex and may be modified by other antioxidants and by XRCC1 genotype.
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PMID:Lycopene intake and prostate cancer risk: effect modification by plasma antioxidants and the XRCC1 genotype. 1696 36

DNA repair gene alterations have been shown to cause a reduction in DNA repair capacity. We hypothesised that DNA repair gene polymorphisms may be risk factors for prostate cancer (PC). To test this hypothesis, DNA samples from 165 cases of prostate cancer and healthy controls were analyzed by PCR-RFLP to determine the genotypic frequency of three DNA repair genes (XRCC1, XPC and XRCC7). We found that the frequency of 939Gln variant at XPC Lys939Gln was significantly lower in PC cases (OR=0.39, P=0.016). Haplotype analysis of XRCC1 Arg194Trp (C/T) and Arg399Gln (G/A) revealed that the frequency of the T-A haplotype was significantly higher in PC patients. This is the first report on the studies of XPC and XRCC1 Arg194Trp polymorphisms in PC, and our present data suggest that XPC Lys939Gln and the T-A haplotype of XRCC1 Arg194Trp and Arg399Gln may be risk factors for PC in Japanese.
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PMID:Polymorphisms of DNA repair genes are risk factors for prostate cancer. 1719 15

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.
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PMID:Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer. 1858 55

Radiation therapy is a potentially curative, important treatment option in localized prostate cancer. However, at 8 years after radiation therapy, even in the best risk subset of patients, approximately 10% of patients will experience clinical disease recurrence. The identification of molecular markers of treatment success or failure may allow for the development of strategies to further improve treatment outcomes. Herein, we investigated five molecular markers of DNA repair. 513 patients with castrate-resistant prostate cancer (CRPC), including 284 patients who received radiotherapy, 229 patients without radiotherapy and 152 healthy individuals were genotyped for five polymorphisms in DNA excision repair genes:ERCC1 N118N (500C>T), XPD K751Q (2282A>C), XRCC1 R194W (685C>T), XRCC1 R399Q (1301G>A) and PARP1 V762A(2446T>C). The distribution of genetic polymorphisms in the patients with CRPC and in healthy controls was compared,and the association between the polymorphisms and overall survival was investigated. The polymorphisms evaluated did not show differences between the patient group and the healthy controls, nor did they show a trend toward an association with survival. However, in the radiation treated subgroup, the median survival time was associated with the XRCC1 haplotype. The median survival time was 11.75 years for patients with the R399Q AA /R194W CC haplotype,12.17 years for patients with the R399Q AG/R194W CC haplotype, 6.665 years for patients with the R399Q AG/R194WCT haplotype, and 6.21 years for patients with the R399Q GG/R194W CT haplotype (p = 0.034). This association was not found when all patients were investigated. We conclude that the genetic polymorphisms in XRCC1 may affect the outcome in patients who received radiotherapy for localized prostate cancer.
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PMID:Genetic polymorphisms in XRCC1 associated with radiation therapy in prostate cancer. 2049 66

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