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Sökning: WFRF:(Grotmol Tom)

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  • Aschim, Elin L, et al. (författare)
  • The RsaI polymorphism in the ER{beta} gene is associated with male infertility.
  • 2005
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 1945-7197. ; 90:Jul 5, s. 5343-5348
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Hypospadias, cryptorchidism, testicular cancer, and low semen quality have been proposed as being parts of the testicular dysgenesis syndrome (TDS) hypothetically due to changes in the androgen- estrogen balance in utero. Estrogens and estrogen receptors (ERs) play a role in regulating testicular function. ER beta contains two silent polymorphisms, RsaI (G1082A) and AluI (G1730A). Objective: We investigated the significance of these polymorphisms in the etiology of disorders being part of TDS. Setting: The patients were recruited consecutively through university hospital clinics. Participants: Four groups of Caucasian patients were included: 106 men from infertile couples with a sperm concentration less than 5 x 106 spermatozoa/ ml, 86 testicular cancer patients, 51 boys with hypospadias, and 23 cases with cryptorchidism. Military conscripts (n = 186) with sperm concentration higher than 5 x 10(6) spermatozoa/ ml served as controls. Main Outcome Measures: ER beta polymorphisms RsaI and AluI were determined by allele-specific PCR. In addition, reproductive hormone analyses were performed in controls and infertile men. Results: Compared with the controls, the frequency of the heterozygous RsaI AG-genotype was three times higher in infertile men (13.2 vs. 4.3%; P = 0.01). The heterozygous RsaI AG-genotype was associated with an approximately 20% reduction in LH concentration, compared with the wild-type RsaI GG genotype in both controls and infertile men. Subjects with testicular cancer, hypospadias, or cryptorchidism did not differ from controls regarding the frequency of any of the polymorphisms. Conclusions: Polymorphisms in ER beta may have modulating effects on human spermatogenesis. The phenotype of TDS seems to be, at least partly, determined by the genotype.
  • Bjørge, Tone, et al. (författare)
  • Reproductive history and risk of colorectal adenocarcinoma in parous women a Nordic population-based case-control study
  • 2016
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 115:11, s. 1416-1420
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.</p>
  • Hoff, Geir, et al. (författare)
  • Risk of colorectal cancer seven years after flexible sigmoidoscopy screening : randomised controlled trial
  • 2009
  • Ingår i: BMJ. British Medical Journal (International Ed.). - 0959-8146 .- 0959-535X. ; 338, s. b1846
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>OBJECTIVE: To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy. DESIGN: Randomised controlled trial. SETTING: Population based screening in two areas in Norway-city of Oslo and Telemark county (urban and mixed urban and rural populations). PARTICIPANTS: 55 736 men and women aged 55-64 years. INTERVENTION: Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing (n=13 823) compared with no screening (n=41 913). MAIN OUTCOME MEASURES: Planned end points were cumulative incidence and mortality of colorectal cancer after 5, 10, and 15 years. This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years. RESULTS: No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups (134.5 v 131.9 cases per 100 000 person years). In intention to screen analysis, a trend towards reduced colorectal cancer mortality was found (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16). For attenders compared with controls, a statistically significant reduction in mortality was apparent for both total colorectal cancer (hazard ratio 0.41, 0.21 to 0.82, P=0.011) and rectosigmoidal cancer (0.24, 0.08 to 0.76, P=0.016). CONCLUSIONS: A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years' follow-up. Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders, with a reduction of 59% for any location of colorectal cancer and 76% for rectosigmoidal cancer in per protocol analysis, an analysis prone to selection bias. TRIAL REGISTRATION: Clinical trials NCT00119912.</p>
  • Ruhayel, Yasir, et al. (författare)
  • Seasonal variation in serum concentrations of reproductive hormones and urinary excretion of 6-sulfatoxymelatonin in men living north and south of the Arctic Circle: a longitudinal study.
  • 2007
  • Ingår i: Clinical Endocrinology. - Wiley-Blackwell. - 1365-2265. ; 67:1, s. 85-92
  • Tidskriftsartikel (refereegranskat)abstract
    • bjective Seasonal variation in photoperiod or temperature may influence human reproductive biology. The present study evaluated whether seasonal changes occurred in the levels of reproductive hormones and the major melatonin metabolite, 6-sulfatoxymelatonin (aMT6s), in populations exposed to extreme variation in photoperiod and temperature. Design Two separate cohorts of Norwegian men were recruited from the general population in either of two locations: Tromso (69.5 degrees N, n = 92) or Oslo (60 degrees N, n = 112), located north and south of the Arctic Circle (66.5 degrees N), respectively. Measurements Four blood and 12-h overnight urine samples were obtained on separate occasions over a 12-month period, including during the photoperiod maximum and minimum. Serum concentrations of FSH, LH, testosterone (T), oestradiol (E-2), SHBG and the urinary excretion of aMT6s were assessed. Results Statistical analysis using generalized estimating equations indicated that LH levels were lowest during early winter in both locations (both P = 0.01). In Tromso, free T and E-2 concentrations peaked during early winter (P = 0.02 and 0.003, respectively). In Oslo, free T levels were lowest during early winter (P = 0.06) whereas E-2 levels were lowest during late summer (P < 0.001). Urinary aMT6s concentrations were lowest during early summer in Tromso and Oslo. Concentrations peaked during early winter in Tromso (P < 0.001) and during late winter in Oslo (P < 0.001). Conclusion LH levels exhibited similar changes in both locations, whereas the patterns of changes of the sex steroid concentrations differed, possibly indicating different underlying mechanisms. Excretion of aMT6s was lowest during early summer in both locations, indicating that the long natural photoperiod was sufficient to cause suppression of melatonin secretion. Whether these changes have any biological significance remains uncertain.
  • Sköld, Camilla, et al. (författare)
  • Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women
  • 2018
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 143:8, s. 1858-1867
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) 30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend &lt; 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. &lt;25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. &lt;25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [&gt;= 4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), p(heterogeneity)&lt;0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.</p>
  • Troisi, Rebecca, et al. (författare)
  • Pregnancy complications and subsequent breast cancer risk in the mother : a Nordic population-based case-control study
  • 2018
  • Ingår i: International Journal of Cancer. - WILEY. - 0020-7136 .- 1097-0215. ; 143:8, s. 1904-1913
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population-based case-control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967-2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78-0.97), gestational hypertension (OR 0.90; 95% CI 0.86-0.93) and preeclampsia (OR 0.91; 95% CI 0.88-0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98-1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.</p>
  • Zhang, Yan Dora, et al. (författare)
  • Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
  • 2020
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence. In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.</p>
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