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  • Kapeu, Aline Simen, et al. (author)
  • Is Smoking an Independent Risk Factor for Invasive Cervical Cancer? A Nested Case-Control Study Within Nordic Biobanks
  • 2009
  • In: American Journal of Epidemiology. - Baltimore, Md. : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 169:4, s. 480-488
  • Journal article (peer-reviewed)abstract
    • The strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio = 2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio = 3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke.
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  • Malmqvist, Erik, 1980-, et al. (author)
  • The ethics of implementing human papillomavirus vaccination in developed countries
  • 2011
  • In: Medicine, Health care and Philosophy. - : Springer Science and Business Media LLC. - 1386-7423 .- 1572-8633. ; 14:1, s. 19-27
  • Journal article (peer-reviewed)abstract
    • Human papillomavirus (HPV) infection is the world’s most common sexually transmitted infection. It is a prerequisite for cervical cancer, the second most common cause of death in cancer among women worldwide, and is also believed to cause other anogenital and head and neck cancers. Vaccines that protect against the most common cancer-causing HPV types have recently become available, and different countries have taken different approaches to implementing vaccination. This paper examines the ethics of alternative HPV vaccination strategies. It devotes particular attention to the major arguments for and against one strategy: voluntary, publicly funded vaccination for all adolescent boys and girls. This approach seems attractive because it would protect more people against cervical cancer and other HPV-related cancers than less inclusive alternatives, without the sacrifice of autonomy that a comparably broad compulsory programme would require. Also, the herd immunity that it would likely generate would protect those who remain unvaccinated, a major advantage from a justice perspective. However, there is a possibility that a HPV vaccination programme targeting all adolescents of both sexes is not considered sufficiently cost-effective. Also, it might pose more difficulties for achieving informed consent than comparable vaccination programmes against other diseases. Ultimately, society’s choice of HPV vaccination strategy requires careful consideration not only of the values at stake but also of available and emerging scientific evidence.
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  • Tedeschi, Rosamaria, et al. (author)
  • Activation of maternal Epstein-Barr virus infection and risk of acute leukemia in the offspring
  • 2007
  • In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 165:2, s. 134-137
  • Journal article (peer-reviewed)abstract
    • After identifying an association between maternal Epstein-Barr virus (EBV) reactivation and acute lymphoblastic leukemia (ALL), the authors analyzed a nested case-control study within Finnish and Icelandic maternity cohorts with 7 million years of follow-up to confirm EBV's role in ALL. Offspring of 550,000 mothers were followed up to age 15 years during 1975-1997 by national cancer registries to identify leukemia cases. Mothers of cases and three quarters of matched mothers of controls were identified by national population registers. First-trimester sera from mothers of 304 ALL cases and 39 non-ALL cases and from 943 mothers of controls were analyzed for antibodies to viral capsid antigen, early antigen, and EBV transactivator protein ZEBRA. Relative risk, estimated as odds ratio (95% confidence interval), was adjusted for birth order and sibship size. Combining early antigen and/or ZEBRA immunoglobulin G antibodies with the presence of viral capsid antigen immunoglobulin M antibodies did not increase the estimate for ALL risk for viral capsid antigen immunoglobulin M alone (odds ratio = 1.9, 95% confidence interval: 1.2, 3.0). Both ZEBRA immunoglobulin G antibodies and viral capsid antigen immunoglobulin M antibodies were associated with an increased risk of non-ALL in the offspring (odds ratio = 4.5, 95% confidence interval: 1.3, 16; odds ratio = 5.6, 95% confidence interval: 1.1, 29, respectively), suggesting EBV reactivation in the mothers of non-ALL cases. EBV reactivation may be associated with a proportion of childhood leukemia.
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  • Tedeschi, Rosamaria, et al. (author)
  • No Risk of Maternal EBV Infection for Childhood Leukemia.
  • 2009
  • In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 18, s. 2790-2792
  • Journal article (peer-reviewed)abstract
    • We performed a large nested case-control study within the Finnish and Icelandic maternity cohorts to verify/falsify the association of maternal EBV infection with an increased risk of acute lymphoblastic leukemia (ALL) in the offspring found in previous studies. All hematologic malignancies diagnosed among children born during 1983 to 2006 in Finland and 1997 to 2005 in Iceland were identified through national cancer registries. For each index mother of a leukemia case, three matched control mothers with cancer-free offspring were identified. First trimester sera from 561 ALL and 144 non-ALL index mothers and from 2,105 control mothers were analyzed for antibodies to EBV viral capsid antigen (IgG and IgM), early antigen (IgG) and ZEBRA protein (IgG). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for birth order and sib-ship size were calculated. Overall, there was no evidence of increased risk of ALL associated to EBV viral capsid antigen IgM (odds ratio, 0.9; 95% confidence interval, 0.5-1.8). The early antigen and ZEBRA antibodies (EBV reactivation markers) were also not associated with risk. The data argue against a role of EBV in ALL. (Cancer Epidemiol Biomarkers Prev 2009;18(10):OF1-3).
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  • Valve, Paivi, et al. (author)
  • LINDA - a solution-focused low-intensity intervention aimed at improving health behaviors of young females : a cluster-randomized controlled trial
  • 2013
  • In: BMC Public Health. - : BMC. - 1471-2458. ; 13
  • Journal article (peer-reviewed)abstract
    • Background: We aimed to develop and evaluate the effectiveness of an individualized, long-term support lifestyle counseling approach in promoting healthy physical activity, improving dietary and sleeping behaviors, and preventing weight gain in young females. The counseling approach's intensity was designed to be low enough to be implementable in primary health care. Methods: Young women (n = 3,059, age at baseline 17-21 years) attending a population-based human papilloma virus vaccination trial (clinicaltrials.gov identifier: NCT00122681) in 15 vaccination centers in different communities across Finland, were cluster-randomized into intervention and control arms of the LINDA intervention. Both intervention and control arms received counseling on sexual health and contraception from the study nurses as part of the vaccination trial. Additionally, the LINDA intervention arm (n = 1,537) received a 20-minute individualized lifestyle counseling session followed by further support at the six-monthly follow-up visits of the vaccination trial, in total for 1.5-2.5 years. The LINDA solution-focused brief therapy intervention focused on healthy physical activity, and dietary and sleeping behaviors, based on the needs and interests of the participants. Anthropometrics were measured, and data on health-related behaviors were collected using self-report questionnaires at baseline and after the intervention at 1.5-2.5 years. Results: In the intervention arm, 37% vs. 31% in the control arm made an overall improvement in their health behaviors concerning physical activity, meal regularity and/or earlier bedtime (NNT = 18, 95% CI = 11-50). The per-protocol analysis further revealed that 30% of those who actually received lifestyle change support on healthy physical activity behaviors improved their physical activity level vs. 23% in the control group (NNT = 15, 95% CI = 9-38). Respectively, 36% of those who received support on healthy sleeping behaviors went to sleep earlier before school-/work-days after the intervention vs. 28% in the control group (NNT = 13, 95% CI = 7-61). Dinner irregularity increased in both groups, but less in the intervention group among those who received support on healthy dietary behaviors (NNT = 15, 95% CI = 9-46). There was no effect on weight gain between baseline and study end-point. Conclusions: The solution-focused brief therapy intervention, with individually tailored content, helped to make small, long-term overall improvements in health behaviors concerning physical activity, meal regularity and/or earlier bedtime.
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  • Agborsangaya, Calypse, et al. (author)
  • The effects of storage time and sampling season on the stability of serum 25-hydroxy vitamin D and androstenedione
  • 2010
  • In: Nutrition and Cancer. - : Informa UK Limited. - 0163-5581 .- 1532-7914. ; 62:1, s. 51-57
  • Journal article (peer-reviewed)abstract
    • Knowledge of the stability of serum samples stored in large biobanks is pivotal for reliable assessment of hormone-dependent disease risks. We studied the effects of sample storage time and season of serum sampling on the stability of 25-hydroxy vitamin D (25-OHD) and androstenedione in a stratified random sample of 402 women, using paired sera from the Finnish Maternity Cohort. Serum samples selected were donated between 6 and 24 yr ago. The storage time did not affect serum 25-OHD and androstenedione levels. However, there was a significant mean difference in the 25-OHD levels of sera withdrawn during winter (first sample) vs. during summer (second sample; -18.4 nmol/l, P ≤ 0.001). Also at the individual level, there were significant differences in average 25-OHD levels between individuals with the paired sera taken at winter–winter compared with other alternatives (summer–winter, winter–summer, and summer–summer). The androstenedione levels showed no such differences. Long-term storage does not affect serum 25-OHD and androstenedione levels, but sampling season is an important determinant of 25-OHD levels. Stored serum samples can be used to study disease associations with both hormones. However, sampling season needs to be taken into account for 25-OHD by considering matching and stratification and, if possible, serial sampling.
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  • Angle, Susanna, et al. (author)
  • Three factor eating questionnaire-R18 as a measure of cognitive restraint, uncontrolled eating and emotional eating in a sample of young Finnish females
  • 2009
  • In: International Journal of Behavioral Nutrition and Physical Activity. - : BIOMED CENTRAL LTD. - 1479-5868. ; 6
  • Journal article (peer-reviewed)abstract
    • Background: The aim of the study was to examine the construct validity of the Three-Factor Eating Questionnaire-R18 (TFEQ-R18), a measure of eating behaviour, and to evaluate cognitive restraint, uncontrolled eating and emotional eating in a sample of adolescent and young adult females of different weights. Methods: Subjects were 2 997 females, aged 17 to 20 years, who participated in a phase III human papillomavirus vaccination trial in Finland in 2004-2009. Self-administered questionnaires and weight and height measurements were used. The factor structure of the TFEQ-R18 was verified by factor analysis. Connections between measured eating behaviour and Body Mass Index (BMI) were tested using analysis of variance. Results: The original factor structure of the TFEQ-R18 was replicated: six of the eighteen items measured cognitive restraint, nine measured uncontrolled eating, and three measured emotional eating. On average, higher BMI was associated with higher levels of cognitive restraint (p < 0.001) and emotional eating (p < 0.001), but not with uncontrolled eating. Conclusion: Structural validity of the TFEQ-R18 was good in this sample of young Finnish females with a varying range of body weights. Use of the instrument as a measure of eating behaviour was thus corroborated. Connections of restrained and emotional eating with BMI were in accordance with previous findings from young females.
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  • Bzhalava, Davit, et al. (author)
  • Phylogenetically diverse TT virus viremia among pregnant women
  • 2012
  • In: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 432:2, s. 427-434
  • Journal article (peer-reviewed)abstract
    • Infections during pregnancy have been suggested to be involved in childhood leukemias. We used high-throughput sequencing to describe the viruses most readily detectable in serum samples of pregnant women. Serum DNA of 112 mothers to leukemic children was amplified using whole genome amplification. Sequencing identified one TT virus (TTV) isolate belonging to a known type and two putatively new TTVs. For 22 mothers, we also performed ITV amplification by general primer PCR before sequencing. This detected 39 TTVs, two of which were identical to the Tilts found after whole genome amplification. Altogether, we found 40 TTV isolates, 29 of which were putatively new types (similarities ranging from 89% to 69%). In conclusion, high throughput sequencing is useful to describe the known or unknown viruses that are present in serum samples of pregnant women. (C) 2012 Elsevier Inc. All rights reserved.
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  • Bzhalava, Davit, et al. (author)
  • Viremia during pregnancy and risk of childhood leukemia and lymphomas in the offspring: Nested case-control study.
  • 2016
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 138:9, s. 2212-2220
  • Journal article (peer-reviewed)abstract
    • A possible role for infections of the pregnant mother in the development of childhood acute leukemias and lymphomas has been suggested. However, no specific infectious agent has been identified. Offspring of 74,000 mothers who had serum samples taken during pregnancy and stored in a large-scale biobank were followed up to the age of 15 years (750,000 person years) through over-generation linkages between the biobank files, the Swedish national population and cancer registers to identify incident leukemia/lymphoma cases in the offspring. First-trimester sera from mothers of 47 cases and 47 matched controls were retrieved and analyzed using next generation sequencing. Anelloviruses were the most common viruses detected, found in 37/47 cases and in 40/47 controls, respectively (OR: 0.6, 95% CI: 0.2-1.9). None of the detected viruses was associated with leukemia/lymphoma in the offspring. Viremia during pregnancy was common, but no association with leukemia/lymphoma risk in the offspring was found.
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  • Castro, Felipe A, et al. (author)
  • Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach.
  • 2009
  • In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 125:8, s. 1851-1858
  • Journal article (peer-reviewed)abstract
    • High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. (c) 2009 UICC.
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  • Chen, Tianhui, et al. (author)
  • Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer
  • 2011
  • In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:2, s. 324-336
  • 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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  • Dahlström, Lisen Arnheim, et al. (author)
  • Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer
  • 2011
  • In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:12, s. 2541-2550
  • Journal article (peer-reviewed)abstract
    • Background: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects. Methods: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI. Results: Exposure to HPV16 was the strongest risk factor for cervical cancer [ OR = 2.4; 95% confidence interval (CI), 2.0-3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2-3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3-4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9-1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8-1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5-2.3). Conclusions: A large prospective study has assessed the role of different STIs in cervical cancer. Impact: Prospective evidence supports cofactor role of some STI in cervical cancer. Cancer Epidemiol Biomarkers Prev; 20(12); 2541-50. (C) 2011 AACR.
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22.
  • Dillner, Joakim, et al. (author)
  • Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.
  • 2010
  • In: BMJ: British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 341
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). DESIGN: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. SETTING: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. PARTICIPANTS: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. INTERVENTION: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. MAIN OUTCOME MEASURES: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. RESULTS: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. CONCLUSIONS: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. TRIAL REGISTRATIONS: NCT00092521 and NCT00092534.
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  • Dillner, Lena, et al. (author)
  • Strengthening prevention programs to eliminate cervical cancer in the Nordic countries.
  • 2008
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 87:5, s. 489-498
  • Research review (peer-reviewed)abstract
    • Disease trend studies based on birth cohort analysis and serological studies indicate that recent generations have a higher prevalence of oncogenic Human Papilloma Virus (HPV) types, and are likely to be at higher risk of cancer than previous generations. This implies that prevention strategies to protect young populations from HPV-associated cancers need to be strengthened, and hence organized implementation of vaccination and better screening programs are being considered. In this context, randomized large-scale policy evaluations will be instrumental in accelerating disease control and improve effective prevention programs. This report shares experiences from Nordic countries with examples of prevention strategies through vaccination and cervical screening. The same principles as set up for organized programs and new HPV technologies may apply for screening and vaccination as key tools to eliminate cervical cancer in the Nordic countries and globally.
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24.
  • Fortner, Renée T, et al. (author)
  • Early pregnancy sex steroids and maternal breast cancer : a nested case-control study
  • 2014
  • In: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:23, s. 6958-6967
  • Journal article (peer-reviewed)abstract
    • Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); Ptrend = 0.01], and inversely associated with breast cancer diagnosed at age ≥40 [4th vs. 1st quartile OR 0.71 (0.51-1.00); Ptrend = 0.02]. Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER(+)/PR(+) disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER(-)/PR(-) breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor-negative cancers is needed to further characterize this association.
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25.
  • Fortner, Renée T, et al. (author)
  • Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer : Results from the Finnish Maternity Cohort
  • 2017
  • In: Cancer Research. - 0008-5472 .- 1538-7445. ; 77:1, s. 134-141
  • Journal article (peer-reviewed)abstract
    • Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case-control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case-control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94-1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., <5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64-1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86-2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk. 
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