Lichen sclerosus and risk of cancer Halonen, Pia; Jakobsson, Maija; Heikinheimo, Oskari ...
International journal of cancer,
1 May 2017, Letnik:
140, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population‐based Finnish Cancer Registry data to further study this connection.
We identified all ...women with the diagnosis of LS (n = 7,616) listed in the Finnish Hospital Discharge Registry from 1970 to 2012. The cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses until 2014. Standardized incidence ratios (SIRs) were calculated for different cancers by dividing the observed numbers of cancers by expected ones. The expected numbers were based on national cancer incidence rates.
During the follow‐up period, we found 812 cancers among patients with LS (SIR: 1.13, 95% CI 1.05–1.21). LS was associated with an increased risk of vulvar (182 cases, SIR: 33.6, 95% CI 28.9–38.6) and vaginal cancer (4 cases, SIR: 3.69, 95% CI 1.01–9.44). The risk of cancers of the uterine cervix and lung was significantly decreased.
LS is associated with an increased risk for vulvar and vaginal cancer. These data are important when designing the care of women diagnosed with LS.
What's new?
Does it or doesn't it? Evidence is scant on whether the skin condition lichen sclerosus leads to cancer. These authors conducted the largest study to date, looking at 7,600 patients for nearly a decade. Among these patients, 800 cancer cases arose. Analysis showed that lichen sclerosus does increase one's risk of developing vulvar or vaginal cancer, but decreases the risk of cervical cancer, although the numbers were few due to the rarity of LS and these cancers.
To assess the risks of gynecologic cancer according to the type of endometriosis in women with surgically verified endometriosis.
This is a population-based study of women with surgically verified ...endometriosis retrieved from the Finnish Hospital Discharge Register 1987-2012 (N=49,933); the subtypes of ovarian (n=23,210), peritoneal (n=20,187), and deep infiltrating (n=2,372) endometriosis were analyzed separately. Gynecologic cancers were obtained from the Finnish Cancer Registry. The outcome measure was the standardized incidence ratio (95% CI) calculated as the ratio between the observed to the expected number of cancers and defined for each gynecologic cancer and further stratified according to the histology, follow-up time since surgery, and age at follow-up. The follow-up was 838,685 person-years, and the Finnish female population served as the reference.
Endometriosis was associated with increased risk of ovarian cancer (standardized incidence ratio 1.76 95% CI 1.47-2.08), especially with endometrioid (3.12 2.15-4.38) and clear cell (5.17 3.20-7.89) histologic type and to a lesser extent with serous type (1.37 1.02-1.80). The risk of ovarian cancer was highest among women with ovarian endometriosis and especially for endometrioid (4.72 2.75-7.56) and clear cell (10.1 5.50-16.9) ovarian cancer, occurring 5-10 years after the index surgery. The overall risk of ovarian cancer was not increased among women with peritoneal and deep infiltrating endometriosis. However, peritoneal endometriosis was associated with a twofold increase in risk of endometrioid histology. The risk of endometrial cancer was not altered in the entire cohort. The standardized incidence ratio for precancerous cervical lesions was 0.81 (0.71-0.92) and for invasive squamous cell carcinoma of the cervical cancer 0.46 (0.20-0.91).
The excess risk of ovarian cancer among women with ovarian endometriosis translates into two excess cases per 1,000 patients followed for 10 years. Acknowledging these risks is important when planning long-term management of women with endometriosis.
Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women’s health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in ...leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions. We also explored the transcriptional consequences of 7q22, 22q, and 1p deletions, aiming to identify possible target genes. We investigated 94 leiomyomas and 60 corresponding myometrial tissues using exon arrays, whole genome sequencing, and SNP arrays. This integrative approach revealed subtype-specific expression changes in key driver pathways, including Wnt/β-catenin, Prolactin, and insulin-like growth factor (IGF)1 signaling. Leiomyomas with HMGA2 aberrations displayed highly significant up-regulation of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1), suggesting that HMGA2 promotes tumorigenesis through PLAG1 activation. This was supported by the identification of genetic PLAG1 alterations resulting in expression signatures as seen in leiomyomas with HMGA2 aberrations. RAD51 paralog B (RAD51B), the preferential translocation partner of HMGA2, was up-regulated in MED12 mutant lesions, suggesting a role for this gene in the genesis of leiomyomas. FH-deficient leiomyomas were uniquely characterized by activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes, supporting the hypothesis that accumulation of fumarate leads to activation of the oncogenic transcription factor NRF2. This study emphasizes the need for molecular stratification in leiomyoma research and possibly in clinical practice as well. Further research is needed to determine whether the candidate biomarkers presented herein can provide guidance for managing the millions of patients affected by these lesions.
Uterine leiomyomas (ULs) are benign tumors that are a major burden to women's health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of ...the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by
- highlighting the role of telomere maintenance -
and
. Genes involved in genitourinary development,
and uterine stem cell marker antigen
formed another strong subgroup. The combined risk contributed by the 22 loci was associated with
mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis, and in part explain the more frequent occurrence of UL in women of African origin.
In this nationwide study we assessed the use and factors associated with future in vitro fertilization (IVF) treatment after induced abortion.
The study population was collected by means of record ...linkage between Finnish national registers. All women who underwent induced abortion between 2000 and 2009 in Finland were identified through the Register of Induced Abortions (n = 88 522). The study group consisted of women who underwent induced abortion and subsequently had an IVF treatment (n = 379); the comparison group were all women who had a spontaneous pregnancy and delivery 12-24 months after the index abortion (n = 7434). Demographic characteristics at the time of index abortion, and factors associated with the abortion (gestational age at abortion, indication and method of abortion, complications after abortion) were compared between the study groups. Logistic regression was used to assess whether some of the demographic characteristics or abortion associated factors increased the use of IVF treatment in the future.
The proportion of women with IVF treatment after induced abortion in the whole cohort was 0.4%. Women needing IVF treatment were older, of a higher socioeconomic status, and had fewer previous induced abortions and deliveries compared to women in the comparison group. No statistically significant differences were observed in the gestational age (≤ 12 weeks or >12 weeks of gestation) at abortion, method or complications of abortion. In multivariable analysis higher age increased, and history of previous deliveries or one or two abortions decreased the use of IVF.
Infertility necessitating the use of IVF treatment after induced abortion is uncommon. The factors associated with use of IVF after abortion are those generally recognized as risk factors of infertility. Abortion-related outcomes are not associated with an increased need of future IVF-treatment.
Background Endometriosis is associated with increased risk of clear cell ovarian cancer and has even suggested being an etiological factor for this cancer. Association between endometriosis and ...extraovarian clear cell cancers is unclear. This study aimed to assess the association between surgically diagnosed endometriosis and risk of extraovarian clear cell cancers according to the type of endometriosis (i.e., ovarian, peritoneal, and other endometriosis) and the site of clear cell cancer. Methods In this register-based historic cohort study we identified all women with surgically diagnosed endometriosis from the Finnish Hospital Discharge Registry 1987-2012. Data on extraovarian clear cell cancers of these women were obtained from the Finnish Cancer Registry. The follow-up started January 1.sup.st, 2007 or at endometriosis diagnosis (if later), and ended at emigration, death or on the December 31.sup.st, 2014. Standardized incidence ratios were calculated for each site of clear cell carcinoma (intestine, kidney, urinary tract, gynecological organs other than ovary), using the Finnish female population as reference. Results The endometriosis cohort consisted of 48,996 women, including 22,745 women with ovarian and 19,809 women with peritoneal endometriosis. Altogether 23 extraovarian clear cell cancers were observed during 367,386 person-years of follow-up. The risk of extraovarian clear cell cancer was not increased among all women with surgically diagnosed endometriosis (standardized incidence ratio 0.89, 95% confidence interval 0.56-1.33) nor in different types of endometriosis. The incidence of clear cell cancer in any specific site was not increased either. Conclusions The risk of extraovarian clear cell cancers in women with surgically diagnosed endometriosis is similar to that in the general population in Finland.
Summary Background Medical abortion with mifepristone and prostaglandins is well established. We compared clinical assessment with self-assessment of abortion outcome. Methods This randomised, ...controlled, non-inferiority trial was done in four clinics in Austria, Finland, Norway, and Sweden, between Aug 16, 2011, and Jan 31, 2013. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation were eligible. Computer-generated block randomisation (block size ten) assigned women in a 1:1 ratio to attend routine clinical follow-up or to self-assess outcome at home with a semiquantitative urine human chorionic gonadotropin (hCG) test 1–3 weeks after abortion. The primary outcome was the percentage of women with complete abortion not requiring further medical or surgical intervention within 3 months. Analysis was per protocol and by intention to treat. The non-inferiority margin was five percentage points. This trial is registered with ClinicalTrials.gov , number NCT01487213. Findings 924 women were assigned routine follow-up (n=466) or self-assessment (n=458) and included in the intention-to-treat analysis. 901 were included in the per-protocol analysis (n=446 and n=455, respectively). Complete abortion was reported in 432 (95%) of 455 in the routine follow-up group and 419 (94%) of 446 women in the self-assessment group (crude difference −1·0, 95% CI −4·0 to 2·0). 20 (4%) women in the routine follow-up group and 17 (4%) in the self-assessment group required surgery. No women in the routine follow-up group versus three in the self-assessment group had undetected continuing pregnancies. Eight (1·8%) and one (0·2%) women, respectively, had infections (p=0·038). Interpretation Self-assessment was non-inferior to routine follow-up and could save resources. Funding Nordic Federation of Obstetrics and Gynaecology, European Society of Contraception, Helsinki University Central Hospital, Helse Finnmark, Swedish Research Council, and Stockholm County Council and Karolinska University Hospital.
Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex ...development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B's ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.
Introduction
Increasing awareness of endometriosis in adolescents requires data on the nature of the disease and its management. Our objective was to investigate the subtypes of surgically confirmed ...endometriosis in adolescents (aged <20 years) and trends in the incidence rates and endometriosis‐related procedures during the study period, 1987–2012.
Material and Methods
In this register‐based cohort study, we identified 526 adolescents receiving their initial surgical diagnosis of endometriosis between 1987 and 2012 from the Finnish Hospital Discharge Register. The age‐specific incidence rate of surgically confirmed endometriosis was calculated by dividing the number of adolescents during specific periods by person‐years. We calculated the relative differences in incidence rates between the periods using crude incidence ratios.
Results
Adolescents were divided into three age groups, <17, 17–18, and 19 years, which comprised 8.2% (43/526), 39.7% (209/526), and 52.1% (274/526) of the study cohort, respectively. Peritoneal endometriosis and ovarian endometriosis were the most common types (379/526 72% and 119/526 23%, respectively). The incidence rate of surgically confirmed endometriosis per 100 000 person‐years varied from 5.63 (95% confidence interval CI 4.24–7.33) to 11.42 (95% CI 9.64–13.44). The incidence rate in 2001–2005 was significantly higher and was 1.6‐ to 2.0‐fold that of the periods 1987–1990 and 2006–2012, respectively. Comparing the periods in which International Classification of Diseases, Ninth Revision (ICD‐9; 1987–1995) and Tenth Revision (ICD‐10; 1996–2012) codes were used, the use of laparoscopy (78.2% vs 88.9%), day surgery (10.3% vs 31.6%), and procedures for ovarian (18.8% vs 34.1%) and deep (0.6% vs 10.8%) endometriosis increased. The types of endometriosis and procedures did not differ between the age groups.
Conclusions
Peritoneal endometriosis was the most common type of endometriosis overall and by age group. During the 26‐year period, the incidence rate of initial surgical diagnosis of endometriosis peaked in 2001–2005 and decreased thereafter. The proportion of procedures performed for ovarian and deep endometriosis increased, as did the use of laparoscopy and day surgery.
The incidence rate of surgically confirmed endometriosis in adolescents peaked in 2001‐2005 but decreased thereafter. Peritoneal endometriosis was the most common type of endometriosis in adolescents, and no differences in the types of endometriosis between the age groups were observed.
Monitoring factors related to hormonal contraception (HC) use is essential to evaluating public health strategies and promoting access to contraception. We aimed to examine municipal social and ...health indicators of HC use at the population level, and to identify patterns of inequality across Finnish municipalities.
We identified all women (15-49 years) with a redeemed HC prescription in Finland in 2017 (n = 294,445), and a control group of non-users. Municipal social and health indicators at the population level were retrieved from the nationwide Statistics and Indicator Bank. Differences between the groups across 309 municipalities were calculated, and associations of municipal-specific proportions of HC users with municipal-specific indicators were studied using LASSO (Least Absolute Shrinkage and Selection Operator) models.
Sociodemographic differences between HC users and non-users were non-homogenous across municipalities. Indicators positively associated with HC use included: larger population and higher proportions of population aged 16-24 years, of household-dwelling units with one person, of persons with higher education, and of divorces among those aged 25-64. Lower HC use was associated with higher proportions of Swedish-speaking population, of those aged 7-15 years, of young people not in education/training, and of household-dwelling units in overcrowded conditions. Lower HC use was also associated with indicators of outpatient and inpatient healthcare, and of municipal finances in welfare and healthcare.
Sociodemographic differences in relation to HC use exist across Finnish municipalities. Municipal indicators of social structure, health and welfare, and investment in and use of healthcare services are related to HC use.
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