| 1. |
- Antai, Diddy, et al.
(författare)
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Inequities in Under-Five Mortality in Nigeria : Differentials by Religious Affiliation of the Mother
- 2009
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Ingår i: Journal of religion and health. - : Springer Science and Business Media LLC. - 0022-4197 .- 1573-6571. ; 48:3, s. 290-304
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Tidskriftsartikel (refereegranskat)abstract
- Observations in Nigeria have indicated polio vaccination refusal related to religion that ultimately affected child morbidity and mortality. This study assessed the role of religion in under-five (0-59 months) mortality using a cross-sectional, nationally representative sample of 7,620 women aged 15-49 years from the 2003 Nigeria Demographic and Health Survey and included 6,029 children. Results show that mother's affiliation to Traditional indigenous religion is significantly associated with increased under-five mortality. Multivariable modelling demonstrated that this association is explained by differential use of maternal and child health services, specifically attendance to prenatal care. To reduce child health inequity, these results need to be incorporated in the formulation of child health policies geared towards achieving a high degree of attendance to prenatal care, irrespective of religious affiliation.
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| 2. |
- Cox, Angela, et al.
(författare)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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| 3. |
- Exarchou, Sofia, et al.
(författare)
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Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study
- 2024
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:4, s. 446-456
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo compare all-cause mortality and causes of death between patients with psoriatic arthritis (PsA) and the general population in Sweden.MethodsAdults with at least one main PsA diagnosis (International Classification of Diseases-10: L40.5/M07.0-M07.3) from outpatient rheumatology/internal medicine departments 2001-2017 were identified from the National Patient Register. Each case was matched to five population comparator-subjects on sex/county/age at the case's first arthritis diagnosis. Follow-up ran from 1 January 2007, or from first PsA diagnosis thereafter, until death, emigration or 31 December 2018. Mortality was assessed overall, and stratified by sex and duration since diagnosis (diagnosis before/after 1 January 2007), using matched Cox proportional hazard regression (excluding/including adjustments for comorbidity) or Breslow test, as appropriate. Incidence rate ratios (IRR) of death, overall and stratified by sex/duration since diagnosis/age, as well as causes of death in PsA cases and comparator-subjects were also described.ResultsAll-cause mortality was elevated in PsA (HR: 1.11 (95% CI: 1.07 to 1.16); IRR: 1.18 (95% CI: 1.13 to 1.22)), mainly driven by increased risks in women (HR: 1.23 (95% CI: 1.16 to 1.30)) and cases with longer time since diagnosis (HR: 1.18 (95% CI: 1.12 to 1.25)). IRR of death were significantly increased for all ages except below 40 years, with the numerically highest point-estimates for ages 40-59 years. When adjusted for comorbidity, however, the elevated mortality risk in PsA disappeared. Causes of death were similar among PsA cases/comparator-subjects, with cardiovascular disease and malignancy as the leading causes.ConclusionsMortality risk in PsA in Sweden was about 10% higher than in the general population, driven by excess comorbidity and with increased risks mainly in women and patients with longer disease duration.
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| 4. |
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| 5. |
- Hall, Per, et al.
(författare)
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Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis : a cohort study
- 2006
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 4, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results: HRT use in patients with estrogen receptor ( ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
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| 6. |
- Holmqvist, Marie E, et al.
(författare)
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No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis : results from two Swedish population-based rheumatoid arthritis cohorts.
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:10, s. 2861-2869
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well-known increased risk of IHD in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA. METHODS: We assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population-based case-control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases. We used data from the Swedish Early Arthritis Register study and the Swedish Epidemiologic Investigation of Rheumatoid Arthritis case-control study and from general population controls. Information on IHD, MI, and angina pectoris was obtained from the nationwide Hospital Discharge Register and from self reports. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) to compare the prevalence of a history of IHD/MI/angina pectoris among patients with RA with that among population controls. RESULTS: We could not detect any increased occurrence of IHD, MI, or angina pectoris before the onset of symptoms of RA, regardless of whether data on IHD were obtained from the Hospital Discharge Register or were self reported. As detected in the Hospital Discharge Register, the OR for IHD overall was 1.0 (95% CI 0.9-1.1), the OR for MI was 1.0 (95% CI 0.9-1.1), and the OR for angina pectoris was 1.0 (95% CI 0.9-1.2). CONCLUSION: Shared risk factors or susceptibilities for RA and IHD are likely to contribute less than RA-related factors to the increased occurrence of IHD in patients with manifest RA. Nonetheless, the existence of shared factors associated with longer latency until the occurrence of IHD cannot be excluded.
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| 7. |
- Khanolkar, Amal R., et al.
(författare)
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Preterm and postterm birth in immigrant- and Swedish-born parents : a population register-based study
- 2015
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 30:5, s. 435-447
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Tidskriftsartikel (refereegranskat)abstract
- Ethnic minorities/immigrant groups tend to have increased risk for preterm birth. Less is known about this risk in diverse immigrant groups, couples of mixed ethnic-origin and in relation to duration of residence. Data from the Swedish Medical Birth Register on 1,028,303 mothers who gave birth to 1,766,026 singleton live born infants (1982–2002), was linked to the Education and Total Population Registers. Immigrant parents were identified by country of birth. Risk of early preterm, late preterm and postterm birth was analyzed using multinomial logistic regression. Polish, Yugoslavian, Iranian, South Asian, East Asian and Sub-Saharan African parents, Swedish mothers who had children with non-Swedish fathers, and parents from two different immigrant groups had higher risk of early preterm birth [adjusted relative risk (RR) (95 % CI) 1.76 (1.24–2.50), 1.57 (1.31–1.87), 1.67 (1.30–2.14), 1.52 (1.07–2.16), 1.51 (1.08–2.10), 2.03 (1.32–3.12), 1.56 (1.45–1.67), and 1.55 (1.35–1.77) respectively] compared to Swedish-born parents. South Asian, Sub-Saharan African, and East Asian immigrants had a higher risk of late preterm birth compared to Swedish-born parents. North African and Middle Eastern, Somali, and Ethiopian/Eritrean groups had increased risk of postterm birth [adjusted RR 1.31 (1.16–1.47), 2.57 (2.31–2.86), 1.85 (1.67–2.04) respectively]. Adjustment for covariates did not substantially change associations. Immigrant mothers resident <3 years had higher risk for early preterm and postterm birth compared to residents >10 years [adjusted RR 1.46 (1.24–1.71) and 1.16 (1.11–1.23) respectively]. In addition to higher risk of preterm birth in select immigrant groups, some immigrant groups are also at higher risk of postterm birth. Shorter duration of residence is associated with higher risk of non-term deliveries.
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| 8. |
- Lindström, Ulf, et al.
(författare)
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Biological treatment of ankylosing spondylitis : A nationwide study of treatment trajectories on a patient level in clinical practice
- 2019
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is substantial evidence that patients with ankylosing spondylitis (AS) have high response rates to tumour necrosis factor inhibitors (TNFi), a low likelihood of successful treatment termination, but yet a limited drug retention. Whereas several reports have assessed drug retention rates for TNFi in AS, there are few, if any, studies investigating the actual treatment trajectories on a patient level, including subsequent therapy changes and dose reductions, of individual patients. The aim of this study was to describe 5-year treatment trajectories in patients with ankylosing spondylitis (AS) starting a first TNFi. Methods: Bio-naïve patients with AS starting a TNFi in 2006-2015 were identified in the nationwide Swedish Rheumatology Quality register and followed until 31 December 2015. All changes in their anti-rheumatic treatment during follow-up were recorded. To further increase precision, these data were complimented by information on the amount of prescribed subcutaneous TNFi collected from pharmacies during each year, retrieved from the Swedish Prescribed Drug Register. Results: Two thousand five hundred ninety patients started a first TNFi 2006-2015, and after 1 year, 74% remained on their first TNFi. However, after 5 years, this figure was only 46%, although at that time 63% were still on treatment with any biologic, while 30% had no anti-rheumatic treatment at all. After discontinuing the first TNFi, 46% switched directly to a second TNFi, but the drug retention for the second and third TNFi grew successively shorter compared to that for the first TNFi. In contrast, patients remaining on treatment with their first subcutaneous TNFi gradually reduced the dose, so that during the fifth year of treatment only 66% had collected ≥ 75% of the defined daily doses for that year. Conclusion: Less than half of patients with AS will remain on their first TNFi after 5 years, but most are still on a biologic. While patients remaining on treatment with their first TNFi appear to be able to reduce the dose over time, a large proportion cycle through several biologics, and 1/3 have no anti-rheumatic treatment after 5 years. This indicates the importance of thorough follow-up programs as well as a need for alternative therapeutic options.
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| 9. |
- Lindström, Ulf, et al.
(författare)
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Impact of extra-articular spondyloarthritis manifestations and comorbidities on drug retention of a first TNF-inhibitor in ankylosing spondylitis : A population-based nationwide study
- 2018
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess the impact of extra-articular spondyloarthritis (SpA) manifestations (anterior uveitis, psoriasis and inflammatory bowel disease (IBD)), and of comorbidities, on tumour necrosis factor alpha inhibitor (TNFi) drug retention in ankylosing spondylitis (AS). Methods We identified all bio-naïve patients with AS starting a first ever TNFi July 2006 to December 2015 from the Swedish Rheumatology Quality register and followed these from treatment start through December 2015. We determined the presence of extra-articular SpA-manifestations, comorbidities (cardiovascular disease, affective disease, diabetes, malignancies, chronic lung disease and kidney disease) and socioeconomic status before TNFi start, through linkage to five other national registers, and calculated, for each factor, crude and adjusted HRs for discontinuing the TNFi. Results 2577 patients with AS (71% men) started a first TNFi during the study period. 27% had a history of anterior uveitis, 6% psoriasis and 7% IBD. Anterior uveitis was associated with a superior TNFi drug retention (HR 0.72; 0.62 to 0.83), psoriasis with an inferior (HR 1.48; 1.18 to 1.86), whereas IBD did not affect TNFi drug retention. The effect of the SpA manifestations on TNFi drug retention was of a similar magnitude to that of the comorbidities. Conclusions In AS, anterior uveitis and psoriasis, but not IBD, affect TNFi drug retention. Possible explanations include differential effects of TNFi on these extra-articular SpA manifestations, or inherent differences in AS, associated with the inflammatory phenotype. Further, comorbidities and socioeconomy affect TNFi drug retention to a similar magnitude as the SpA manifestations, and should, as such, receive due attention in clinical practice.
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| 10. |
- Low, Yen Ling, et al.
(författare)
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Multi-Variant Pathway Association Analysis Reveals the Importance of Genetic Determinants of Estrogen Metabolism in Breast and Endometrial Cancer Susceptibility
- 2010
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 6:7, s. e1001012-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML)-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (rho(global) = 0.034) and endometrial (rho(global) = 0.052) cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (rho(global) = 0.008) and endometrial cancer (rho(global) = 0.014). The sub-pathway association was validated in the Finnish sample of breast cancer (rho(global) = 0.015). Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (rho(global) = 0.0003). Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite genetic determinants related to the androgen-estrogen conversion are important for the induction of two hormone-associated cancers, particularly for the hormone-driven breast tumour subtypes.
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| 11. |
- Orgeas, C, et al.
(författare)
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Breast cancer incidence after hormonal infertility treatment in Sweden: a cohort study
- 2009
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Ingår i: Am J Obstet Gynecol. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 200:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the impact of infertility treatment with causes of infertility on incidence of breast cancer. STUDY DESIGN: Historical prospective cohort study of 1135 women attending major university clinics for treatment of infertility in Sweden, 1961-1976. Women were classified as users of clomiphene citrate or gonadotropins, or a combination of both therapies. Standardized incidence ratios were calculated to estimate relative risk of breast cancer. RESULTS: We observed 54 cases of breast cancer during 1961-2004, which did not significantly exceed those expected. Users of high-dose clomiphene citrate had an almost 2-fold increased risk (standardized incidence ratio, 1.90; 95% confidence interval, 1.08-3.35). This association was more pronounced among women referred for nonovulatory factors, with 3-fold increased risk (standardized incidence ratio, 3.00; 95% confidence interval, 1.35-6.67). CONCLUSION: No overall increased risk for breast cancer was shown with infertility treatment. Women with nonovulatory causes treated with high-dose clomiphene citrate therapy may have an elevated risk for breast cancer.
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| 12. |
- Pawitan, Yudi, et al.
(författare)
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Gene expression profiling spares early breast cancer patients from adjuvant therapy : derived and validated in two population-based cohorts
- 2005
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7:6, s. R953-64
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. METHODS: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. CONCLUSION: We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy.
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| 13. |
- Wedrén, Sara, et al.
(författare)
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Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer
- 2007
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 16:9, s. 1775-1783
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAG(n) and VDR A(n) genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (/=22 repeats for AR and /=19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAG(n) repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with >/=20 repeats. Women carrying two VDR alleles with <21 A(n) were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated.
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| 14. |
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| 15. |
- Wedrén, Sara, et al.
(författare)
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Estrogen receptor alpha gene polymorphism and endometrial cancer risk : a case-control study
- 2008
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8, s. 322-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Estrogen is an established endometrial carcinogen. One of the most important mediators of estrogenic action is the estrogen receptor alpha. We have investigated whether polymorphic variation in the estrogen receptor alpha gene (ESR1) is associated with endometrial cancer risk. METHODS: In 702 cases with invasive endometrial cancer and 1563 controls, we genotyped five markers in ESR1 and used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI). RESULTS: We found an association between rs2234670, rs2234693, as well as rs9340799, markers in strong linkage disequilibrium (LD), and endometrial cancer risk. The association with rs9340799 was the strongest, OR 0.75 (CI 0.60-0.93) for heterozygous and OR 0.53 (CI 0.37-0.77) for homozygous rare compared to those homozygous for the most common allele. Haplotype models did not fit better to the data than single marker models. CONCLUSION: We found that intronic variation in ESR1 was associated with endometrial cancer risk.
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| 16. |
- Wedrén, Sara
(författare)
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Genetic susceptibility to breast and endometrial cancer
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hormones are central in the carcinogenic process in the breast and in the uterine epithelium. Individual genetically determined variation in the response to hormonal influence may alter susceptibility to breast and endometrial cancers. Many small studies of this hypothesis have generated inconclusive results. Since the effect of any genetic variant is expected to be modest, large studies are needed to draw reliable conclusions. Also, there may be interaction between genetic and lifestyle factors that needs to be considered. To adress these issues, we conducted a large population-based case-control study that incorporated genetic and lifestyle exposures. We investigated common variants in the genes for the estrogen metabolizing enzymes catechol-Omethyl transferase (COMT) and cytochrome P450 1B1 (CYP1B1) and in the estrogen (ESR1), androgen (AR) and vitamin D receptors (VDR), selected from previous literature, in relation to breast and endometrial cancer risk. We genotyped 1569 breast cancer patients, 707 endometrial cancer patients and 1729 partly shared population controls. All participants had previously provided extensive information via a questionnaire about lifestyle factors such as reproductive history, body size, and use of menopausal hormone preparations. We found that a COMT allele that confers high enzyme activity (c.324/474A>G G) was associated with increased risk for lobular breast cancer, but not with breast cancer risk overall. The CYP1B1 variants, c.355G>T, c.4326C>G, and c.4390A>G, were not associated with breast cancer risk. The common ESR1 c.454-351A>G allele was associated with relatively higher cancer risk compared with the rare allele, although in breast cancer only when considered in a haplotype with c.975C>G. The endometrial cancer risk in women homozygous for the rare c.454-351A>G allele was just half of the risk in those homozygous for the common allele. The AR CAGn and VDR An were not associated with breast cancer risk. In exploratory subgroup analyses stratified according to lifestyle factors, we found that in women with diabetes mellitus the high activity COMT allele was associated with an increased risk for breast cancer. In women who had used menopausal hormones for at least four years the CYP1B1 c.4326C>G G allele conferred increased breast cancer risk. The association between the ESR1 c.454-35 1A>G and c.975C>G AC haplotype and breast cancer was stronger among women with a BMI above 30. Women who carried two short alleles of VDR An had a halved risk for breast cancer, irrespective of parity. The most persuasive association in this work was the similar relation between variation in ESR1 and breast and endometrial cancer. A stronger association with endometrial cancer was expected due to its apparently lower degree of etiological complexity relative to breast cancer. The estrogen receptor is crucial in estrogen stimulation and thus the prior probability of this gene being linked to breast and endometrial cancer risk was high. The remaining results indeed add to the body of evidence regarding breast and endometrial cancer susceptibility but the statistically significant associations may well be due to chance.
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| 17. |
- Wedrén, Sara, et al.
(författare)
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Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk : a case control study
- 2004
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 6:4, s. R437-49
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk. METHODS: We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. RESULTS: There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. CONCLUSION: We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.
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| 18. |
- Weiderpass, Elisabete, et al.
(författare)
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Estrogen receptor alpha gene polymorphisms and endometrial cancer risk
- 2000
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 21:4, s. 623-627
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Tidskriftsartikel (refereegranskat)abstract
- Since the estrogen receptor alpha (ER) is an important mediator of hormonal responses such as proliferation in estrogen-sensitive tissues, we hypothesized that polymorphisms in the ER gene could be functional and associated with endometrial cancer risk. We performed a population-based case-control study in Sweden, focusing on restriction fragment length polymorphisms for XbaI and PvuII and an upstream TA repeat polymorphism. In the main analysis, 154 cases and 205 controls who never used hormone replacement therapy took part and we calculated age-adjusted and multivariate odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. The XbaI X allele appeared to confer a reduced risk for endometrial cancer. The multivariate OR for the XX genotype was 0.52 (95% CI 0.21-1.29) compared to the xx genotype and there were suggestions of decreasing risk with increasing number of X alleles (P for trend = 0.07). The PvuII PP genotype was also associated with a non-significantly decreased risk for endometrial cancer (multivariate OR 0.70, 95% CI 0.34-1.44) compared with the pp genotype (P for trend = 0.43). The multivariate OR for two short TA (<19 repeats) alleles versus two long alleles was 1.54 (95% CI 0. 73-3.27) and there were suggestions of increasing risk with increasing number of short alleles (P for trend = 0.26). We observed the same pattern of results in an expanded group of subjects, which included women who had used hormone replacement (in total 288 cases and 392 controls). Our data suggest that variants of the ER gene may be associated with an altered risk of endometrial cancer.
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| 19. |
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