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- Almquist, Martin, et al.
(författare)
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Serum levels of vitamin D, PTH, calcium and breast cancer risk - a prospective nested case-control study.
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 127:9, s. 2159-2168
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies indicate that calcium and its regulating hormones, i.e. parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to pre-diagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH and calcium using a nested case-control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analysed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD(3), PTH and calcium. There was a weak, non-significant inverse association between breast cancer risk and 25OHD(3), and the OR for the 2(nd), 3(rd) and 4(th) quartiles, as compared to the first, were 0.84(0.60-1.15), 0.84(0.60-1.17), and 0.93(0.66-1.33). Serum calcium was positively associated with breast cancer in pre-menopausal women (OR for the 4(th) quartile = 3.10:1.33-7.22 and p for quartile trend=0.04), and in women with BMI>25 (OR for the 4(th) quartile=1.94:1.12-3.37 and p for trend<0.01). There was no association between baseline serum PTH and breast cancer risk. (c) 2010 UICC.
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- Dahlström, Lisen Arnheim, et al.
(författare)
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Prospective study of human papillomavirus and risk of cervical adenocarcinoma.
- 2010
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 127:8, s. 1923-30
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.
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- Dossus, Laure, et al.
(författare)
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Reproductive risk factors and endometrial cancer : the European prospective investigation into cancer and nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:2, s. 442-451
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
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- Fuchs, Dieter, et al.
(författare)
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Metronomic administration of the drug GMX1777, a cellular NAD synthesis inhibitor, results in neuroblastoma regression and vessel maturation without inducing drug resistance
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:12, s. 2772-2789
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Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma is a rapidly growing tumor with a survival rate below 50%. A new treatment strategy is to administer chemotherapeutic drugs metronomically, i.e. at lower doses and frequent intervals. The aim of the study was to investigate the effects of GMX1777, a chemotherapeutic drug affecting cellular energy metabolism, in a mouse model for high-risk neuroblastoma.Female SCID mice were injected s.c. with MYCN-amplified human neuroblastoma cells and randomized to either treatment with GMX1777 or vehicle. In some animals, treatment was discontinued allowing tumor relapse. Treatment response was evaluated using the Pediatric Preclinical Testing Program (PPTP). Immunohistochemistry and qRT-PCR was performed on tumor cryosections to investigate the microscopic and molecular changes in tumors in response to GMX1777.Despite an increase in vessel density, tumor regression and a high group response score according to PPTP criteria was induced by GMX1777 without inducing drug resistance. Treatment resulted in inhibition of tumor cell proliferation, vessel maturation, reduced hypoxia, increased infiltration of MHC class II negative macrophages and expansion of the non-vascular stromal compartment. Decreased stromal VEGF-A and PDGF-B mRNA in response to treatment together with the structural data suggest a "deactivation" or "silencing" of the tumor stroma as a paracrine entity.In conclusion, GMX1777 was highly efficient against high-risk neuroblastoma xenografts through modulation of both the tumor cell and stromal compartment.
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