Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology (original) (raw)
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Polymorphism in Women with Sporadic Breast Cancer
2009
The cytochrome P450 family (CYPs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. We hypothesise that polymorphisms of CYP17 and CYP19 gene can predict higher incidence of breast cancer. In the present work the distribution of genotypes and frequency of alleles of the T/C polymorphism in promoter region of CYP17 and Trp/Arg polymorphism in codon 39 of CYP19 gene in breast cancer women were investigated. The genetic polymorphisms analysis was performed by amplifying DNA by PCR-RFLP methods in 100 sporadic breast cancer cases. The distribution of the genotypes of the T/C polymorphism of CYP17 in patients differed significantly (p 0.05) from those predicted by the Hardy-Weinberg distribution. The results support the hypothesis that the T/C polymorphism of CYP17 gene may be associated with the incidence of breast cancer in women from Lodz region of Poland.
Journal of Molecular Biomarkers & Diagnosis, 2014
Background: Many factors may play a role in the susceptibility to the breast cancer. Oxidative stress may be one of these. Polymorphisms of genes such as paraoxonase I (PON I) and glyoxalase I (GLO I) may influence individual susceptibility to breast cancer. In the present study, we have conducted a case-control study in order to examine the possible relation between GLO I A111E and PON I Q192R/L55M polymorphisms with the risk of breast cancer. Methods: The three polymorphisms were characterized in 144 breast cancer postmenopausal patients and in 152 healthy women by PCR/RFLP methods using DNA from lymphocytes. Results: Among the three polymorphisms, only PON I L55M polymorphism was associated with the patient's age and, more precisely, the heterozygous genotype that is more represented in women aged between 51-69 years. In addition, we found that individuals with the PON192 Q/R-R/R genotypes and PON55 L/M-M/M genotypes had a significantly higher risk of breast cancer compared with the other genotypes. The genotypes PON55 L/M and PON192 Q/R showed significant association with lymph nodes positivity (p < 0.001) and with a high nuclear grading (p < 0.001), respectively. Conversely the genotypes GLO I AE/EE were associated with a low nuclear grading. Conclusions: We believe that the combination of the three polymorphisms may be a more predictive factor for the risk of this neoplasia in each single examined case.
Thrita, 2016
Background: Multiple drug resistance in breast cancer patients is one of the most important problems when it comes to the treatment of this disease. In this regard, polymorphisms in DNA sequences play a key role in pharmacokinetics and pharmacodynamics. ABCC1 gene encodes the Multidrug Resistance-Associated Protein 1 (MRP1) protein, which transports many chemotherapy drugs or cellular physiological substances through the cell membrane. As a result, suppression, genetic variations and changes in the expression of this gene may change the drug's distribution, cytotoxicity and clinical outcomes. Objectives: We performed this study to determine the prevalence of different variants of ABCC1 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) (rs3743527 and rs129081) in breast cancer patients and healthy controls. Materials and Methods: We analyzed the prevalence of different alleles of these polymorphisms on DNA extracted from whole blood of 44 patients with breast cancer and 25 healthy controls. We checked C/G variants of rs129081 by performing nestedpolymerase chain reaction (PCR) and allele specific-polymerase chain reaction (AS-PCR). Analysis of C/T alleles in rs3743527 was done using PCR-restriction fragment length polymorphism (RFLP). The results were then confirmed by sequencing. Results: No significant correlation was seen in rs3743527 and rs129081 polymorphism's allelic and genotypic frequencies between the patient group and control individuals (P value > 0.05). The average frequencies of rs129081 G and C alleles was 40 (58%) and 29 (42%), respectively. In our sample the average frequencies of rs3743527 C and T alleles, were 41 (61%) and 28 (39%), respectively. The results of chi-square test showed strong correlations between the incidences of various genotypes in both groups (P value = 0). On average, 27%, 26% and 16% of participants had genotype CC/GG, CT/CG and TT/CC, respectively. Conclusions: Taken together, distribution and frequencies of rs129081 and rs3743527 variants in the patient group and control individuals may not correlate with susceptibility to breast cancer; however, more detailed studies are needed to confirm these results.
European Journal of Human Genetics, 2007
The average length of linkage disequilibrium (LD) blocks in European populations is about 22 kb. In this study, we have selected 20 genes with LD blocks larger than 60 kb (with a median length of 88 kb) from a total of 121 cancer-related genes. We observed limited haplotype diversity, with an average of three haplotypes per gene accounting for more than 90% of the diversity, two of these being a Yin-Yang pair in 95% of the LD blocks. The mean frequency of the most common haplotype in the Spanish population was just below 50%, similar to those for the HapMap CEU and African samples, but lower than the 60% observed in Asian samples. Genes involved in the regulation of nucleobases and nucleic acid metabolism were overrepresented among these 20 genes with long LD blocks (eight genes ATM, BRCA1, BRCA2, ERCC6, MLH1, MSH3, RAD54B and XRCC4) relative to the other 101 cancer-related genes studied (P ¼ 1.23 Â 10 À6). The ancestral haplotype was observed at a frequency greater than 3 in 67% of the genes either in the Spanish or one of the HapMap sampled populations. When observed, the ancestral haplotype had an average 15% frequency in the Spanish sample, less than half that observed in Asian and African samples. The Spanish Yin-Yang haplotype pair represented over 35% of haplotypes in African samples and over 65% in non-African samples. We detected differences in SNP frequencies between populations for five genes (ALDH2, APC, PIK3CB, RB1 and XRCC4, all with Fst40.4); however, these genes did not show evidence of positive selection. Finally, we found no evidence that the haplotypes formed by SNPs in the 20 genes are associated with breast cancer.
Polymorphisms cMyc-N11S and p27-V109G and breast cancer risk and prognosis
BMC Cancer, 2007
Background: cMyc and p27 are key genes implicated in carcinogenesis. Whether polymorphisms in these genes affect breast cancer risk or prognosis is still unclear. In this study, we focus on a rare nonsynonymous polymorphism in cMyc (N11S) and a common polymorphism in p27 (V109G) and determine their role in risk and prognosis using data collected from the Ontario Breast Cancer Family Registry.
Five Polymorphisms and Breast Cancer Risk: Results from the Breast Cancer Association Consortium
Cancer Epidemiology Biomarkers & Prevention, 2009
Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610 -6)
TP53 (RS1042522) Polymorphism In Breast Cancer
Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 2016
Amaç: TP53 geni temel olarak DNA tamiri, apoptozis, hücre yaşlanması ve hücre döngüsü kontrolünde görev alan en önemli tümör baskılayıcı genlerden biridir. TP53 rs1042522 (Arg72Pro) polimorfizmi tümör baskılama sırasında P53 protein yapısında değişikliğe neden olan bir polimorfizmdir. Bu verilere dayanarak, bu çalışmanın amacı TP53 rs1042522 polimorfizmi ve meme kanseri riski arasındaki ilişkiyi araştırmaktır.Yöntem: TP53 rs1042522 polimorfizmi için 508 meme kanserli kadın hastadan ve 367 sağlıklı kadından alınan periferik kanlardan DNA izole edilerek PCR-RFLP yöntemi ile genotipleme yapıldı. İstatistiksel analiz, %95 güven aralığında χ2 testi ile yapıldı ve Hardy-Weinberg eşitliği (HWE) test edilen hastalar ve kontrol popülasyonu için doğrulandı.Bulgular: Genotip frekansları sırasıyla hasta ve kontrollerde GG alleli için %48.6, %46.3, GC alleli için %40.7, %44.7ve CC alleli için de %10.6, %9.0 şeklindedir. Vaka ve control genotipleri arasında istatistiksel olarak fark olmadığı bulu...
Analysis of CDKN1A polymorphisms:: markers of cancer susceptibility?
Cancer genetics and …, 2003
The CDKN1A (TP21) gene encodes a 21-kD protein that is a critical downstream mediator of wild-type TP53 and an important regulator of the cell cycle. Failure in the function of this gene would be expected to result in abnormal cell proliferation and transformation. Tumor-associated mutations of the coding region of the TP21 are rare. On the other hand, some TP21 polymorphisms have been identified and characterized by single base substitutions. In the present study, we investigated the potential role of TP21 gene polymorphisms in skin, head, and neck tumorigenesis. A total of 261 samples were examined by polymerase chain reaction single-strand conformational analysis, and one mutation at codon 31 and four polymorphisms in exons 2 (codon 55) and 3 [nucleotide (nt)590] and in promoter region (nt2298) were identified. In conclusion, this investigation confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers. Also, our results show significant differences in nt2298 allele frequencies between normal individuals and skin malignant tumors (P Ͻ 0.05). The results suggest that this polymorphism affects TP21 transactivator binding and may be important during the pathogenesis of skin cancer.
Common Genetic Variation in Candidate Genes and Susceptibility to Subtypes of Breast Cancer
Cancer Epidemiology Biomarkers & Prevention, 2009
Association studies have been widely used to search for common low penetrance susceptibility alleles to breast cancer in general. However, breast cancer is a heterogeneous disease and it has been suggested that it may be possible to identify additional susceptibility alleles by restricting analyses to particular subtypes. We used data on 710 SNPs in 120 candidate genes from a large candidate-gene association study of up to 4470 cases and 4560 controls to compare the results of analyses of "overall" breast cancer with sub-group analyses based on the major clinicopathological characteristics of breast cancer (stage, grade, morphology and hormone receptor status). No single nucleotide polymorphism (SNP) was highly significant in overall-effects analysis. Subgroup analysis resulted in substantial reordering of ranks of SNPs, as assessed by the magnitude of the test statistics and some associations that were not significant for an overall effect were detected in sub-groups at a nominal 5% level adjusted for multiple testing. The most significant association, of CCND1 SNP rs3212879 with estrogen receptor negative tumour types (p = 0.001), did not reach genome-wide significance levels. These results demonstrate that it may be possible to detect associations using subgroup analysis that are missed in overall-effects analysis. If the associations we found can be replicated in independent studies they may provide important insights into disease mechanisms in breast cancer.
Association of p53 polymorphisms with breast cancer: a case-control study in Slovak population
Neoplasma
Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. As a transcription factor p53 controls many cell processes and helps in prevention of cancer development. The p53 gene is polymorphic. Polymorphisms can affect the important regions involved in protein tumor suppressor activity. The well-known polymorphisms are the polymorphisms BstUI in exon 4 and MspI in intron 6. Both are supposed to be associated with cancer development. The purpose of this study was to investigate the genotype frequencies and associations of these polymorphisms with breast cancer in Slovak population. We observed the prevalence of BstUIPro (27.47%) and MspIA1 (17.58%) alleles and BstUIPro/Pro (8.79%) and MspIA1/A1 (5.49%) genotypes in breast cancer patients in comparison with controls 23.40%, 14.10%, 5.77%, 1.92% respectively. However the differences were not significant. After division of the cases and controls according to the age the prevalence of the risk alleles and genotypes...