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1.
He XF Wei W Su J Yang ZX Liu Y Zhang Y Ding DP Wang W 《Molecular biology reports》2012,39(5):5125-5134
The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and
A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the
association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls),
and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies
were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed
in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04–1.16) and in additive model (OR = 1.10, 95% CI = 1.03–1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies
were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model.
Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive
model (OR = 0.90, 95% CI = 0.82–0.99) and dominant model (OR = 0.94, 95% CI = 0.89–0.99). In summary, this meta-analysis indicates
that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast
cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M,
A4541G, and A17893G polymorphisms and breast cancer risk. 相似文献
2.
Krupa R Sliwinski T Wisniewska-Jarosinska M Chojnacki J Wasylecka M Dziki L Morawiec J Blasiak J 《Molecular biology reports》2011,38(4):2849-2854
XRCC2 and XRCC3 proteins are structurally and functionally related to RAD51 which play an important role in the homologous
recombination, the process frequently involved in cancer transformation. In our previous work we show that the 135G>C polymorphism
(rs1801320) of the RAD51 gene can modify the effect of the Thr241Met polymorphism (rs861539) of the XRCC3 gene. We tested the association between the 135G>C polymorphism of the RAD51 gene, the Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism (rs3218536) of the XRCC2 gene and colorectal cancer risk and clinicopathological parameters. Polymorphisms were evaluated by restriction fragment
length polymorphism polymerase chain reaction (RFLP-PCR) in 100 patients with invasive adenocarcinoma of the colon and in
100 sex, age and ethnicity matched cancer–free controls. We stratified the patients by genotypes, tumour Duke’s and TNM stage
and calculated the linkage of each genotype with each stratum. Carriers of Arg188Arg/Me241tMet, His188His/Thr241Thr and His188His/G135G
genotypes had an increased risk of colorectal cancer occurrence (OR 5.70, 95% CI 1.10–29.5; OR 12.4, 95% CI 1.63–94.9; OR
5.88, 95% CI 1.21–28.5, respectively). The C135C genotype decreased the risk of colorectal cancer singly (OR 0.06, 95% CI
0.02–0.22) as well as in combination with other two polymorphisms. TNM and Duke’s staging were not related to any of these
polymorphisms. Our results suggest that the 135G>C polymorphism of the RAD51 gene can be an independent marker of colorectal cancer risk. The Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism of the XRCC2 gene can modify the risk of colorectal cancer. 相似文献
3.
The link between loss or defect in functional BRCA1 and predisposition for development of ovarian and breast cancer is well established. Germ-line mutations in BRCA1 are responsible for both hereditary breast and ovarian cancer, which is around 5–10% for all breast and 10–15% of all ovarian
cancer cases. However, majority of cases of ovarian cancer are sporadic in nature. The inactivation of cellular BRCA1 due
to mutations or loss of heterozygosity is one of the most commonly observed events in such cases. Complement-resistant retroviral
BRCA1 vector, MFG-BRCA1, is the only approved gene therapy for ovarian cancer patients by the Federal and Drug Administration.
Given the limited available information, there is a need to evaluate the effects of BRCA1 on the global gene expression pattern
for better understanding the etiology of the disease. Here, we use Ingenuity Pathway Knowledge Base to examine the differential
pattern of global gene expression due to stable expression of BRCA1 in the ovarian cancer cell line, SKOV3. The functional
analysis detected at least five major pathways that were significantly (p < 0.05) altered. These include: cell to cell signaling and interaction, cellular function and maintenance, cellular growth
and proliferation, cell cycle and DNA replication, and recombination repair. In addition, we were able to detect several biologically
relevant genes that are central for various signaling networks involved in cellular homeostasis; TGF-β1, TP53, c-MYC, NF-κB and TNF-α. This report provides a comprehensive rationale for tumor suppressor function(s) of BRCA1 in ovarian carcinogenesis. 相似文献
4.
5.
A number of molecular epidemiological studies have been conducted the screening for BRCA1 and BRCA2 mutations in breast cancer patients with a positive family history of breast and/or ovarian cancer and reported many common
mutations in BRCA1 and BRCA2 associated in breast cancer in different population and different ethnicity. However, it’s still lack of a systematic analysis
on these mutations. To comprehensively evaluate the frequency and distribution of common BRCA1 and BRCA2 mutations which associated with breast cancer risk, we address this issue through system review and meta-analysis on 29 relevant
published studies by conducting a literature search on PubMed and CNKI. 20 common founder germline mutations were identified
from all 29 studies and 4 of BRCA1 (5382insC, 185delAG, 3819del5 and 4153delA) and 2 of BRCA2 (4075delGT, 5802del4) mutations were repeatedly reported twice or more in different articles, respectively. For the BRCA1, after conducting meta-analysis, we found that the overall frequency of 5382insC was 0.09 (95% CI 0.06–0.12), the frequency
of 185delAG was 0.07 (95% CI 0.01–0.13), the frequency of 3819del5 was 0.02 (95% CI 0.01–0.04) and the frequency of 4153delA
was 0.06 (95% CI 0.03–0.09). For the BRCA2, the overall frequency of 4075delGT was 0.02 (95% CI 0.00–0.03) and the frequency of 5802del4 was 0.07 (95% CI 0.04–0.11).
This article provides a set of common mutations for BRCA1 and BRCA2 mutation carriers and the results may help to explore frequencies of BRCA1 and BRCA2 mutations in a given population and will be of significance both for diagnostic testing and for epidemiological studies. 相似文献
6.
The relationship between diet and colorectal cancer has been previously demonstrated and supported with strong epidemiological
evidence. The role of genetic polymorphisms has, however, been less well elaborated upon. We conducted a hospital-based case–control
study including 727 cases and 736 healthy controls to evaluate the associations of the polymorphic phase-I and -II biotransformations
(CYP1A1, CYP1A2, GSTM1, GSTT1, GSTP1, NAT1 and NAT2) and DNA-repair enzymes (XRCC1, XRCC3 and XPD) with the risk of contracting colorectal cancer. We found that men featuring the CYP1A1*2C G/G genotype, the GSTT1 null genotype and XPD 751 with the Gln allele were associated with an elevated risk of colorectal cancer than were men who did not exhibit such genetic features.
Multivariate logistic regression analysis revealed that individuals featuring more than two high-risk genotypes increased
the colorectal-cancer risk 3.1-fold (OR = 3.1, 95% CI = 1.8–5.2). For women, subjects featuring the CYP1A1*2C G/G genotype and the XRCC3 Thr/Thr genotype faced a 3.1-fold greater risk (95% CI = 1.3–7.0) of colorectal cancer when compared to those featuring the CYP1A1*2C A allele and the XRCC3 Met allele. Taken together, this study suggests that polymorphisms of genes involved in biotransformation and DNA repair could
modulate colorectal-cancer risk in Taiwan. 相似文献
7.
8.
Florence Le Calvez-Kelm Javier Oliver Francesca Damiola Nathalie Forey Nivonirina Robinot Geoffroy Durand Catherine Voegele Maxime P. Vallée Graham Byrnes Breast Cancer Family Registry John L. Hopper Melissa C. Southey Irene L. Andrulis Esther M. John Sean V. Tavtigian Fabienne Lesueur 《PloS one》2012,7(12)
Background
Although inherited breast cancer has been associated with germline mutations in genes that are functionally involved in the DNA homologous recombination repair (HRR) pathway, including BRCA1, BRCA2, TP53, ATM, BRIP1, CHEK2 and PALB2, about 70% of breast cancer heritability remains unexplained. Because of their critical functions in maintaining genome integrity and already well-established associations with breast cancer susceptibility, it is likely that additional genes involved in the HRR pathway harbor sequence variants associated with increased risk of breast cancer. RAD51 plays a central biological function in DNA repair and despite the fact that rare, likely dysfunctional variants in three of its five paralogs, RAD51C, RAD51D, and XRCC2, have been associated with breast and/or ovarian cancer risk, no population-based case-control mutation screening data are available for the RAD51 gene. We thus postulated that RAD51 could harbor rare germline mutations that confer increased risk of breast cancer.Methodology/Principal Findings
We screened the coding exons and proximal splice junction regions of the gene for germline sequence variation in 1,330 early-onset breast cancer cases and 1,123 controls from the Breast Cancer Family Registry, using the same population-based sampling and analytical strategy that we developed for assessment of rare sequence variants in ATM and CHEK2. In total, 12 distinct very rare or private variants were characterized in RAD51, with 10 cases (0.75%) and 9 controls (0.80%) carrying such a variant. Variants were either likely neutral missense substitutions (3), silent substitutions (4) or non-coding substitutions (5) that were predicted to have little effect on efficiency of the splicing machinery.Conclusion
Altogether, our data suggest that RAD51 tolerates so little dysfunctional sequence variation that rare variants in the gene contribute little, if anything, to breast cancer susceptibility. 相似文献9.
R.C.K. Panguluri L.C. Brody R. Modali K. Utley L. Adams-Campbell A.A. Day C. Whitfield-Broome G.M. Dunston 《Human genetics》1999,105(1-2):28-31
The breast cancer predisposing gene, BRCA1, was analyzed for germline mutations in 45 African American families at high-risk for hereditary breast cancer. Patients
were considered high-risk if they had a family history of the disease, early onset breast cancer, bilateral breast cancer,
or breast and ovarian cancer. The entire BRCA1 coding and flanking intron regions have been examined by single stranded conformation polymorphism analysis followed by sequencing
of variant bands. Eleven different BRCA1 germline mutations/variations were identified in 7 patients from the 45 high-risk families. Two pathogenic, protein-truncating
mutations were detected in exon 11. A ten base pair tandem duplication, 943ins10, was present in a woman with breast and ovarian
cancer whose first-degree relatives had prostate cancer. A four base pair deletion, 3450del4, was detected in a breast cancer
patient with five cases of breast cancer in the family; two of the proband's sisters with breast cancer also carried the same
mutation. Four amino acid substitutions (Lys1183Arg, Leu1564Pro, Gln1785His, and Glu1794Asp) and four nucleotide substitutions
in intron 22 (IVS22+78 C/A, IVS22+67 T/C, IVS22+8 T/A and IVS22+7 T/C) were observed in patients and not in control subjects.
One early onset breast cancer patient carried five distinct BRCA1 variations, two amino acid substitutions and three substitutions in intron 22. An amino acid substitution in exon 11, Ser1140Gly,
was identified in 3 different unrelated patients and in 6 of 92 control samples. The latter probably represents a benign polymorphism.
Electronic Publication 相似文献
10.
Aim To investigate the possible association of three SNPs, XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population
of northern China. Methods
XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G SNP were genotyped by polymerase-chain reaction (PCR)–restriction fragment length polymorphism (RFLP) analysis in
583 cancer patients (329 ESCC and 254 GCA) and 614 healthy controls. Results The genotype distribution of the XRCC2 C41657T in ESCC and GCA patients were significantly different from that in healthy controls (P values = 0.04 and 0.04 respectively). And a significant difference was found in the allele distribution of GCA patients from
that in controls (P = 0.01). The XRCC2 C41657T polymorphism was associated with a modest enhancement in ESCC risk and GCA risk: OR for C/T genotype was 1.38 (1.01–1.89)
in GCA risk and for T/T genotype was 2.24 (1.10–4.57) in ESCC risk. When stratified for age, smoking status and family history
of UGIC, the C/T genotype showed a modest significant trend on the risk of GCA patients in the groups of age ≤50 years and
non-smokers, the adjusted OR were 2.84 (1.21–6.66) and 1.62 (1.06–2.49). The T/T genotype significantly increased the susceptibility
of GCA patients in negative family history of UGIC (3.04, 1.02–8.32) and to ESCC patients in the group of age >50 years (3.03,
1.31–6.98), Negative family of UGIC (3.03, 1.12–7.07) and smokers (2.64, 1.02–6.83). The genotype and allele distribution
of XRCC2 G4234C and XRCC3 A17893G in ESCC and GCA patients were not significantly different from that in healthy controls (all P values were above 0.05). Conclusion In this study, we found that the C41657T polymorphism of XRCC2 genes might modify the risk of ESCC and GCA development. 相似文献
11.
Gonzalez-Hormazabal P Reyes JM Blanco R Bravo T Carrera I Peralta O Gomez F Waugh E Margarit S Ibañez G Santos JL Jara L 《Molecular biology reports》2012,39(8):8091-8098
Since the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case-control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2-10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age <50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36-18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations. 相似文献
12.
Myszka A Karpinski P Slezak R Czemarmazowicz H Stembalska A Gil J Laczmanska I Bednarczyk D Szmida E Sasiadek MM 《Journal of applied genetics》2011,52(2):185-191
CHEK2 gen encodes cell cycle checkpoint kinase 2 that participates in the DNA repair pathway, cell cycle regulation and apoptosis.
Mutations in CHEK2 gene may result in kinase inactivation or reduce both catalytic activity and capability of binding other proteins. Some studies
indicate that alterations in CHEK2 gene confers increase the risk of breast cancer and some other malignancies, while the results of other studies are inconclusive.
Thus the significance of CHEK2 mutations in aetiology of breast cancer is still debatable. The aim of our study was to evaluate the relationship between
the breast/ovarian cancer and CHEK2 variants by: i) the analysis of the frequency of selected CHEK2 variants in breast and ovarian cancer patients compared to the controls; ii) evaluation of relationships between the certain CHEK2 variants and clinico-histopathological and pedigree data. The study was performed on 284 breast cancer patients, 113 ovarian
cancer patients and 287 healthy women. We revealed the presence of 430T > C, del5395 and IVS2 + 1G > A variants but not 1100delC
in individuals from both study and control groups. We did not observe significant differences between cancer patients and
controls neither in regard to the frequency nor to the type of CHEK2 variants. We discussed the potential application of CHEK2 variants in the evaluation of breast and ovarian cancer predisposition. 相似文献
13.
Suleeporn Sangrajrang Peter Schmezer Iris Burkholder Paolo Boffetta Paul Brennan Andreas Woelfelschneider 《Biomarkers》2013,18(5):523-532
The X-ray repair cross-complementing group 3 gene (XRCC3) belongs to a family of genes responsible for repairing DNA double-strand breaks caused by normal metabolic processes and exposure to ionizing radiation. Polymorphisms in DNA repair genes may alter an individual's capacity to repair damaged DNA and may lead to genetic instability and contribute to malignant transformation. We examined the role of a polymorphism in the XRCC3 gene (rs861529; codon 241: threonine to methionine change) in determining breast cancer risk in Thai women. The study population consisted of 507 breast cancer cases and 425 healthy women. The polymorphism was analysed by fluorescence-based melting curve analysis. The XRCC3 241Met allele was found to be uncommon in the Thai population (frequency 0.07 among cases and 0.05 among controls). Odds ratios (OR) adjusted for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education were calculated for the entire population as well as for pre- and postmenopausal women. There was a significant association between 241Met carrier status and breast cancer risk (OR 1.58, 95% confidence interval (CI) 1.02–2.44). Among postmenopausal women, a slightly higher OR (1.82, 95% CI 0.95–3.51) was found than among premenopausal women (OR 1.48, 95% CI 0.82–2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry. 相似文献
14.
Telomere-related genes play an important role in maintaining the integrity of the telomeric structure that protects chromosome
ends, and telomere dysfunction may lead to tumorigenesis. We evaluated the associations between 39 SNPs, including 38 tag-SNPs
in telomere-related genes (TERT, TRF1, TRF2, TNKS2, and POT1) and one SNP (rs401681) in the TERT-CLPTM1L locus which has been identified as a susceptibility locus to skin cancer in the previous GWAS, and the risk of skin cancer
in a case–control study of Caucasians nested within the Nurses’ Health Study (NHS) among 218 melanoma cases, 285 squamous
cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. Of the 39 SNPs evaluated, ten showed a
nominal significant association with the risk of at least one type of skin cancer. After correction for multiple testing within
each gene, two SNPs in the TERT gene (rs2853676 and rs2242652) and one SNP in the TRF1 gene (rs2981096) showed significant associations with the risk of melanoma. Also, the SNP rs401681 in the TERT-CLPTM1L locus was replicated for the association with melanoma risk. The additive odds ratio (OR) [95% confidence interval (95% CI)]
of these four SNPs (rs2853676[T], rs2242652[A], rs2981096[G], and rs401681[C]) for the risk of melanoma was 1.43 (1.14–1.81),
1.50 (1.14–1.98), 1.87 (1.19–2.91), and 0.73 (0.59–0.91), respectively. Moreover, we found that the rs401681[C] was associated
with shorter relative telomere length (P for trend, 0.05). We did not observe significant associations for SCC or BCC risk. Our study provides evidence for the contribution
of genetic variants in the telomere-maintaining genes to melanoma susceptibility. 相似文献
15.
K. Jelonek A. Gdowicz-Kłosok M. Pietrowska M. Borkowska J. Korfanty J. Rzeszowska-Wolny P. Widłak 《Journal of applied genetics》2010,51(3):343-352
Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor
in various cancer types. Here we analysed polymorphisms in 5 genes involved in DNA repair (XPD Asp312Asn and Lys751Gln,XRCC1 Arg399Gln,APE1 Asp148Glu,NBS1 Glu185Gln, andXPA G-4A) and in a gene involved in regulation of the cell-cycle (CCND1 A870G). We compared their frequencies in groups of colon, head and neck, and breast cancer patients, and 2 healthy control
groups: (1) matched healthy Polish individuals and (2) a NCBI database control group. Highly significant differences in the
distribution of genotypes of theAPE1, XRCC1 andCCND1 genes were found between colon cancer patients and healthy individuals. The 148AspAPE1 allele and the 399GlnXRCC1 allele apparently increased the risk of colon cancer (OR=1.9–2.3 and OR=1.5–2.1, respectively). Additionally, frequencies
ofXPD genotypes differed between healthy controls and patients with colon or head and neck cancer. Importantly, no differences
in the distribution of these polymorphisms were found between healthy controls and breast cancer patients. The data clearly
indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision
repair and DNA-damage-induced responses. 相似文献
16.
Sehrawat B Sridharan M Ghosh S Robson P Cass CE Mackey JR Greiner R Damaraju S 《Human genetics》2011,130(4):529-537
Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However,
the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify
additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed
a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single
nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus
association tests to determine statistical significance for the observed differences in allele frequencies between cases and
controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153
cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from
four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls
in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs
identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage
III from Alberta population or independent validation in Caucasian cohorts elsewhere. 相似文献
17.
Figueroa JD Malats N Real FX Silverman D Kogevinas M Chanock S Welch R Dosemeci M Tardón A Serra C Carrato A García-Closas R Castaño-Vinyals G Rothman N García-Closas M 《Human genetics》2007,121(2):233-242
Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In
order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer
risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish
Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and
smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene
(OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-β (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI)
0.78 (0.63–0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02–1.51) and 1.30 (1.04–1.62),
respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected
BER SNPs, which need to be confirmed in other study populations.
Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
18.
Garner CP Ding YC John EM Ingles SA Olopade OI Huo D Adebamowo C Ogundiran T Neuhausen SL 《Human genetics》2008,123(3):247-255
The insulin-like growth factor (IGF) signaling pathway is thought to play a major role in the etiology of breast cancer. Although
incidence rates of breast cancer overall are lower in African Americans than in Caucasians, African-American women have a
higher incidence under age 40 years, are diagnosed with more advanced disease, and have poorer prognosis. We investigated
the association of breast cancer and genetic variants in genes in the IGF signaling pathway in a population-based case–control
study of African-American women. We found significant associations at a locus encompassing parts of the IGFBP2 and IGFBP5 genes on chromosome 2q35, which we then replicated in a case–control study of Nigerian women. Based on those initial findings,
we genotyped a total of 34 single nucleotide polymorphisms (SNPs) across the region in both study populations. Statistically
significant associations with breast cancer were observed across approximately 50 kb of DNA sequence encompassing three exons
in the 3′ end of IGFBP2 and three exons in the 3′ end of IGFBP5. SNPs were associated with breast cancer risk with P values as low as P = 0.0038 and P = 0.01 in African-Americans and Nigerians, respectively. This study is the first to report associations between genetic variants
in IGFBP2 and IGFBP5 and breast cancer risk. 相似文献
19.
Marie Plourde Alexandra Ferland Penny Soucy Yosr Hamdi Martine Tranchant Francine Durocher Olga Sinilnikova Van Luu The INHERIT BRCAs Jacques Simard 《The Journal of steroid biochemistry and molecular biology》2009,116(3-5):134-153
A family history and estrogen exposure are well-known risk factors for breast cancer. Members of the 17β-hydroxysteroid dehydrogenase family are responsible for important steps in the metabolism of androgens and estrogens in peripheral tissues, including the mammary gland. The crucial biological function of 17β-HSDs renders these genes good candidates for being involved in breast cancer etiology. This study screened for mutations in HSD17B7 and HSD17B12 genes, which encode enzymes involved in estradiol biosynthesis and in AKR1C3, which codes for 17β-HSD type 5 enzyme involved in androgen and progesterone metabolism, to assess whether high penetrance allelic variants in these genes could be involved in breast cancer susceptibility. Mutation screening of 50 breast cancer cases from non-BRCA1/2 high-risk French Canadian families failed to identify germline likely high-risk mutations in HSD17B7, HSD17B12 and AKR1C3 genes. However, 107 sequence variants were identified, including seven missense variants. Assessment of the impact of missense variants on enzymatic activity of the corresponding enzymes revealed no difference in catalytic properties between variants of 17β-HSD types 7 and 12 and wild-type enzymes, while variants p.Glu77Gly and p.Lys183Arg in 17β-HSD type 5 showed a slightly decreased activity. Finally, a haplotype-based approach was used to determine tagging SNPs providing valuable information for studies investigating associations of common variants in these genes with breast cancer risk. 相似文献
20.
《Cell cycle (Georgetown, Tex.)》2013,12(1):90-99
Genetic markers identifying women at an increased risk of developing breast cancer exist, yet the majority of inherited risk remains elusive. While numerous BRCA1 coding sequence mutations are associated with breast cancer risk, BRCA1 mutations account for less then 5% of breast cancer risk. Since 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we tested the hypothesis that such polymorphisms in the 3'UTR of BRCA1 and haplotypes containing these functional polymorphisms may be associated with breast cancer risk. We sequenced the BRCA1 3'UTR from breast cancer patients to identify miRNA disrupting polymorphisms. We further evaluated haplotypes of this region including the identified 3'UTR variants in a large population of controls and breast cancer patients (n=221) with known breast cancer subtypes and ethnicities. We identified three 3'UTR variants in BRCA1 that are polymorphic in breast cancer populations, and haplotype analysis including these variants revealed that breast cancer patients harbor five rare haplotypes not generally found among controls (9.50% for breast cancer chromosomes, 0.11% for control chromosomes, p=0.0001). Three of these rare haplotypes contain the rs8176318 BRCA1 3'UTR functional variant. These haplotypes are not biomarkers for BRCA1 coding mutations, as they are found rarely in BRCA1 mutant breast cancer patients (1/129 patients= 0.78%). These rare BRCA1 haplotypes and 3'UTR SNPs may represent new genetic markers of breast cancer risk. 相似文献