Background Despite potentially relevant chemical differences between filtered and boiled coffee, this study is the first to investigate consumption in relation to the risk of incident cancer. Methods ...Subjects were from the Västerbotten Intervention Project (64,603 participants, including 3,034 cases), with up to 15 years of follow-up. Hazard ratios (HR) were calculated by multivariate Cox regression. Results No associations were found for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, boiled coffee ≥4 versus <1 occasions/day was associated with a reduced risk (HR = 0.52, CI = 0.30-0.88, p trend = 0.247). An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total (HRpremenopausal = 1.69, CI = 0.96-2.98, p trend = 0.015, HRpostmenopausal = 0.60, CI = 0.39-0.93, p trend = 0.006) and filtered coffee (HRpremenopausal = 1.76, CI = 1.04-3.00, p trend = 0.045, HRpostmenopausal = 0.52, CI = 0.30-0.88, p trend = 0.045). Boiled coffee was positively associated with the risk of respiratory tract cancer (HR = 1.81, CI = 1.06-3.08, p trend = 0.084), a finding limited to men. Main results for less common cancer types included total coffee in renal cell cancer (HR = 0.30, CI = 0.11-0.79, p trend = 0.009) and boiled coffee in pancreas cancer (HR = 2.51 CI = 1.15-5.50, p trend = 0.006). Conclusion These findings demonstrate, for the first time, the potential relevance of brewing method in investigations of coffee consumption and cancer risk, but they must be confirmed in future studies.
Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the ...individual level. Telomere length (TL) in two blood samples taken at approximately 10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = -0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = -0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = -0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:--To investigate whether hyperglycemia is associated with increased cancer risk. RESEARCH DESIGN AND METHODS--In the Västerbotten Intervention Project of northern Sweden, fasting and ...postload plasma glucose concentrations were available for 33,293 women and 31,304 men and 2,478 incident cases of cancer were identified. Relative risk (RR) of cancer for levels of fasting and postload glucose was calculated with the use of Poisson models, with adjustment for age, year of recruitment, fasting time, and smoking status. Repeated measurements 10 years after baseline in almost 10,000 subjects were used to correct RRs for random error in glucose measurements. RESULTS:--Total cancer risk in women increased with rising plasma levels of fasting and postload glucose, up to an RR for the top versus bottom quartile of 1.26 (95% CI 1.09-1.47) (Ptrend <0.001) and 1.31 (1.12-1.52) (Ptrend = 0.001), respectively. Correction for random error in glucose measurements increased these risks up to 1.75 (1.32-2.36) and 1.63 (1.26-2.18), respectively. For men, corresponding uncorrected RR was 1.08 (0.92-1.27) (Ptrend = 0.25) and 0.98 (0.83-1.16) (Ptrend = 0.99), respectively. Risk of cancer of the pancreas, endometrium, urinary tract, and of malignant melanoma was statistically significantly associated with high fasting glucose with RRs of 2.49 (1.23-5.45) (Ptrend = 0.006), 1.86 (1.09-3.31) (Ptrend = 0.02), 1.69 (0.95-3.16) (Ptrend = 0.049), and 2.16 (1.14-4.35) (Ptrend = 0.01), respectively. Adjustment for BMI had no material effect on risk estimates. CONCLUSIONS:--The association of hyperglycemia with total cancer risk in women and in women and men combined for several cancer sites, independently of obesity, provides further evidence for an association between abnormal glucose metabolism and cancer.
Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation ...profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers.
The quantitative methylation analysis was performed using the SEQUENOM's EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis.
The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin ...genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3′ untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours odds ratio 2.09, 95% confidence intervals (CIs) 1.19–3.67. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21–3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.
Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of ...postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women.
Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues.
Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues.
Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.
Quantitative data on subsequent cancers after primary cancers provide information on treatment-related risks on second cancers, with implications for therapeutic adverse effects and human ...susceptibility in general. Quantitative data on solid tumors are limited. We focus on survivors of non-Hodgkin's lymphoma (NHL) because the disease is diagnosed at a wide range of ages and treated uniformly primarily with chemotherapy.
The nationwide Swedish Family-Cancer Database included 11.5 million individuals whose cancers were retrieved from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent neoplasms among 28,131 patients with NHL.
The SIR for solid tumors after NHL was 1.65 (2,290 patients) and that for lymphohematopoietic neoplasms was 5.36 (369 patients). Among the 25 most common solid tumors, the SIRs were increased for all but nine sites; the highest SIR (40.8) was observed for spinal meningioma. The SIRs for solid tumors declined in an age-dependent manner from 4.52 in diagnostic age younger than 20 years to 1.12 in diagnostic age 70+ years. In the most common patient groups, the SIRs for solid tumors increased up to 30 years after NHL diagnosis. Because of the high incidence of solid tumors in these age groups, they contributed the largest numbers of therapy-related cases.
These data indicate that age at treatment determines both the magnitude of the initial relative risk and the time-dependent modulation of the response. Therapy-related damage persists at least 30 years and its toll of solid tumors is largest 21 to 30 years after diagnosis.
Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes ...other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend <0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH)D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: Angiogenesis is a necessary step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a major mediator
of breast cancer angiogenesis. Therefore, we investigated the ...association of polymorphisms in the VEGF gene with breast cancer risk and prognostic characteristics of the tumors in a large case-control study.
Experimental Design: We examined three polymorphisms in the VEGF gene (−2578C/A, −1154G/A, and +936C/T) in 571 familial breast cancer cases from Poland and Germany and −2578C/A, −634G/C,
and +936C/T polymorphisms in 974 unselected breast cancer cases from Sweden together with ethnically and geographically selected
controls.
Results: None of the polymorphisms or any haplotype was significantly associated with either familial or unselected breast cancers.
Our study suggests that the +936C/T polymorphism is unlikely to be associated with breast cancer. We also analyzed the unselected
cases for genotypes or haplotypes that associated with tumor characteristics. The −634CC genotype and the −2578/−634 CC haplotype
were significantly associated with high tumor aggressiveness (large tumor size and high histologic grade, P < 0.01) and the −2578AA genotype and the −2578/−634 AG haplotype with low histologic grade tumors ( P = 0.04). The genotypes and haplotypes were not related with other tumor characteristics such as regional or distant metastasis,
stage at diagnosis, or estrogen or progesterone receptor status.
Conclusions: Although none of the polymorphisms studied in the VEGF gene was found to influence susceptibility to breast cancer significantly, some of the VEGF genotypes and haplotypes may influence tumor growth through an altered expression of VEGF and tumor angiogenesis.
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