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| 2. |
- Chen, Tianhui, et al.
(author)
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Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer
- 2011
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:2, s. 324-336
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Journal article (peer-reviewed)abstract
- This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. Impact: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC. Cancer Epidemiol Biomarkers Prev; 20(2); 324-36. ©2010 AACR.
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| 3. |
- Lippi, Giuseppe, et al.
(author)
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Preanalytical quality improvement : from dream to reality
- 2011
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 49:7, s. 1113-1126
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Journal article (peer-reviewed)abstract
- Abstract Laboratory diagnostics (i.e., the total testing process) develops conventionally through a virtual loop, originally referred to as "the brain to brain cycle" by George Lundberg. Throughout this complex cycle, there is an inherent possibility that a mistake might occur. According to reliable data, preanalytical errors still account for nearly 60%-70% of all problems occurring in laboratory diagnostics, most of them attributable to mishandling procedures during collection, handling, preparing or storing the specimens. Although most of these would be "intercepted" before inappropriate reactions are taken, in nearly one fifth of the cases they can produce inappropriate investigations and unjustifiable increase in costs, while generating inappropriate clinical decisions and causing some unfortunate circumstances. Several steps have already been undertaken to increase awareness and establish a governance of this frequently overlooked aspect of the total testing process. Standardization and monitoring preanalytical variables is of foremost importance and is associated with the most efficient and well-organized laboratories, resulting in reduced operational costs and increased revenues. As such, this article is aimed at providing readers with significant updates on the total quality management of the preanalytical phase to endeavour further improvement for patient safety throughout this phase of the total testing process.
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- Papworth, Karin, 1964-
(author)
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Prognostic factors in renal cell carcinoma : evaluation of erythropoietin and its receptor, carbonic anhydrase IX, parathyroid hormone-related protein and osteopontin
- 2011
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Doctoral thesis (other academic/artistic)abstract
- A prognostic factor is a marker or a feature that can be used to estimate the risk of recurrence of disease, metastatic spread and clinical outcome. Despite intensive search for more sophisticated markers in renal cell carcinoma (RCC), few have added prognostic information to earlier described factors like stage of disease, nuclear grade, tumour type, and in metastatic disease; performance status, anaemia, hypercalcaemia and increased erythrocyte sedimentation. In the dominating tumour type, clear cell renal RCC (cRCC), hypoxia is common, leading to an up-regulation of hypoxia inducible factor (HIF). The majority of cRCC have a mutation in the von Hippel Lindau gene (VHL-gene), which regulates HIF and in turn leads to up-regulation of a number of target genes for potential growth factors. The aim of the study was to evaluate the possible prognostic information of a few factors associated to pVHL/HIF, anemia and/or hypercalcaemia in RCC; erythropoietin (EPO) and it´s receptor (EPO-R), carbonic anhydrase IX (CA IX), parathyroid hormone-related protein (PTHrP) and osteopontin (OPN). Patients diagnosed with RCC between 1982-2007 were included in the studies. The tumour tissue expressions of EPO, EPO-R and PTHrP were assessed using immunohistochemistry. Serum/plasma levels of EPO, CA IX, PTHrP and OPN were also analyzed using immunometric methods. Our study demonstrated that the expression of EPO and EPO-R were related, and the expressions differed significantly between RCC types. The serum EPO levels did not associate to the tumour expression of EPO or EPO-R, indicating that circulating EPO derives from other sources than tumour cells. Erythropietin receptor expression was more frequent in advanced stages of disease, but neither EPO, nor EPO-R, were independent prognostic factors for survival. Serum CA IX levels were higher in cRCC compared to papillary RCC (pRCC). In cRCC, the CA IX serum levels correlated positively to TNM stage, but serum CA IX did not add independent prognostic information. Parathyroid hormone-related protein is a cause of hypercalcaemia in malignancy, and we observed that circulating PTHrP related to hypercalcaemia in RCC. The tumour expression of PTHrP associated positively to serum PTHrP, but not to serum calcium. We found an association between PTHrP and OPN in plasma, and both plasma PTHrP and OPN were positively associated to TNM stage. Neither serum/plasma PTHrP nor tumour expression of PTHrP were independent prognostic factors for survival. The serum OPN levels were higher in pRCC but no impact on survival was observed in this RCC type. In contrast, plasma/serum OPN was an independent prognostic factor for disease-specific survival in cRCC. Our results support a role for these factors in RCC. The expressions vary between tumour types, which can be explained by different gene aberrations. Some of the factors have a close relation to para-malignant symptoms like hypercalcaemia. Most of the factors correlate positively to TNM-stage, reflecting a relation to advanced disease. Although expression of EPO, EPO-R, PTHrP and CA IX did not add independent prognostic information, the results might contribute to greater understanding of important mechanisms and associations in RCC. Osteopontin is a strong independent prognostic factor in cRCC, and should be further evaluated as a tool in the clinic when treating RCC patients.
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- Toriola, Adetunji T, et al.
(author)
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Association of serum 25-hydroxyvitamin D (25-OHD) concentrations with maternal sex steroids and IGF-1 hormones during pregnancy
- 2011
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In: Cancer Causes and Control. - : Springer Netherlands. - 0957-5243 .- 1573-7225. ; 22:6, s. 925-928
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Journal article (peer-reviewed)abstract
- BACKGROUND: Vitamin D may influence circulating levels of sex steroid hormones in women during reproductive life, but associations in pregnant women have not been explored.METHODS: Correlation and linear regression models were used to assess the association between sex steroids, (estradiol, progesterone, 17-hydroxyprogesterone, testosterone, and androstenedione), IGF-1, and serum 25-hydroxyvitamin D (25-OHD) concentrations during the first trimester of pregnancy in 106 cancer-free women from the Finnish Maternity Cohort.RESULTS: There was no significant association of serum 25-OHD with any of the hormones measured. One-unit increase in serum 25-OHD concentration was associated with a non-significant 6% increase in estradiol concentrations. Multiparous women had higher levels of vitamin D (40.4 vs. 32.9 nmol/L, p-value = 0.01) than primiparous women.CONCLUSION: Our study does not support an association between maternal serum 25-OHD levels and sex steroids or IGF-I concentrations during the first trimester of pregnancy.
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| 6. |
- Toriola, A T, et al.
(author)
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Changes in pre-diagnostic serum C-reactive protein concentrations and ovarian cancer risk : a longitudinal study
- 2011
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In: Annals of Oncology. - Oxford : Oxford University Press. - 0923-7534 .- 1569-8041. ; 22:8, s. 1916-1921
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Journal article (peer-reviewed)abstract
- BACKGROUND: Evidence suggests that inflammation may be associated with increased risk of ovarian cancer but there is paucity of studies investigating this association, especially using over-time changes in inflammatory biomarkers.MATERIALS AND METHODS: We conducted a prospective population-based case-control study nested within the Finnish Maternity Cohort (FMC). Within the FMC, 170 women with ovarian cancer who had donated serum samples to the cohort twice, ≥1 year apart, before cancer diagnoses were identified. One control per case was matched for age, parity and sampling date.RESULTS: Comparing the highest with lowest tertiles, the odds ratio (OR) of ovarian cancer using the first set of serum samples (mean lag time to cancer diagnosis 9.0 years) was 1.62 [95% confidence interval (CI) 0.93-2.83]. However, analysis conducted using the second set of serum samples donated closer to cancer diagnosis (mean lag time 6.4 years) revealed a significantly increased risk of ovarian cancer comparing extreme tertiles of C-reactive protein (CRP) concentrations; OR 1.96 (95% CI 1.11-3.4). Over time, increases in individuals' CRP concentrations were also associated with increased risk; OR 1.90 (95% CI 1.12-3.23).CONCLUSION: The results suggest that inflammation may precede ovarian cancer since increasing CRP concentrations, both across tertiles and longitudinally at the individual level, were associated with increased risk.
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| 7. |
- Toriola, Adetunji T, et al.
(author)
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Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer
- 2011
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:8, s. 1798-1801
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Journal article (peer-reviewed)abstract
- BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-I have been associated with increased risk of developing breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. This study was conducted to further characterize the association of IGF-I during pregnancy with maternal breast cancer risk.METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women younger than 40 years, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched with each case on age and date at blood donation. Serum IGF-I concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate ORs and 95% CIs.RESULTS: No significant associations were observed between serum IGF-I concentrations and breast cancer risk in both the overall analysis (OR, 1.08; 95% CI, 0.80-1.47) and in analyses stratified by histologic subtype, lag time to cancer diagnosis, age at pregnancy, or age at diagnosis.CONCLUSION: There was no association between IGF-I and maternal breast cancer risk during early pregnancy in this large nested case-control study.IMPACT: Serum IGF-I concentrations during early pregnancy may not be related to maternal risk of developing breast cancer.
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| 8. |
- Toriola, Adetunji T, et al.
(author)
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Determinants of maternal sex steroids during the first half of pregnancy
- 2011
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In: Obstetrics and Gynecology. - New York : Elsevier Science Publ. Co., Inc.. - 0029-7844 .- 1873-233X. ; 118:5, s. 1029-1036
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Journal article (peer-reviewed)abstract
- OBJECTIVE:: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2). METHODS:: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. RESULTS:: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus. CONCLUSION:: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. LEVEL OF EVIDENCE:: II.
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| 9. |
- Toriola, Adetunji T., et al.
(author)
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Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer : a nested case-control study
- 2011
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In: Cancer Causes and Control. - : Springer Netherlands. - 0957-5243 .- 1573-7225. ; 22:11, s. 1607-1611
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Journal article (peer-reviewed)abstract
- Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC). A case-control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case. Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58-1.62) or GCT (OR 1.13, 95% CI 0.51-2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85-1.43) or GCT (OR 0.93, 95% CI 0.68-1.28). Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.
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