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2.
  • Benoni, Henrik, et al. (author)
  • Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study
  • 2020
  • In: Transplant International. - : WILEY. - 0934-0874 .- 1432-2277. ; 33:12, s. 1700-1710
  • Journal article (peer-reviewed)abstract
    • Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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3.
  • Bens, Annet, et al. (author)
  • Worse survival after breast cancer in women with anorexia nervosa
  • 2018
  • In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 168:2, s. 495-500
  • Journal article (peer-reviewed)abstract
    • A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6-3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4-3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3-3.6) among Swedish and Danish women. We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.
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  • Bermejo, Justo Lorenzo, et al. (author)
  • Age-time risk patterns of solid cancers in 60 901 non-Hodgkin lymphoma survivors from Finland, Norway and Sweden
  • 2014
  • In: British Journal of Haematology. - : Wiley. - 0007-1048. ; 164:5, s. 675-683
  • Journal article (peer-reviewed)abstract
    • Survival after non-Hodgkin lymphoma (NHL) has increased thanks to improved treatment but NHL survivors have an increased risk of second neoplasms. The assessment of cancer risk patterns after NHL may help to quantify the late side-effects of therapy. Poisson regression was used to estimate relative risks (RRs) and absolute incidence rates for nine solid tumours based on a nationwide cohort of 60 901 NHL survivors from Finland, Norway and Sweden. Patients were diagnosed between 1980 and 2006 and developed 6815 s neoplasms. NHL patients showed an increased risk of each of the nine investigated cancer sites: prostate and pancreas (both RRs 1.28), breast (1.37), colorectum (1.48), urinary bladder (1.52), stomach and lung (both RRs 1.87), skin (melanoma 2.27) and kidney (2.56). The RRs showed a U-shaped relationship with time after NHL for all nine-second cancer types. NHL diagnosis early in life was a risk factor for the development of second cancers with the exception of melanoma, but a risk excess was even observed in patients diagnosed with NHL at age 80+ years. The present study provides accurate estimates on the adverse late effects of NHL therapy, which should guide the establishment of cancer prevention strategies in NHL survivors.
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5.
  • Bolin, Kristian, et al. (author)
  • Characteristics of finasteride users in comparison with non-users: a Nordic nationwide study based on individual-level data from Denmark, Finland, and Sweden
  • 2020
  • In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 29:4, s. 453-460
  • Journal article (peer-reviewed)abstract
    • Purpose: Published epidemiological studies on the association between finasterideuse and the risk of male breast cancer have been inconclusive due to methodologicallimitations including a few male breast cancer cases included. Determinants of malebreast cancer have been studied, but it remains unexplored whether these are alsorelated to finasteride use and thereby constitute potential confounders. This studyaimed to assess whether there are differences between finasteride users andnonusers with regard to numerous potential confounders.Methods: In total, 246 508 finasteride users (≥35 years) were identified in the pre-scription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden(2005-2014). An equal number of nonusers were sampled. The directed acyclic graph(DAG) methodology was used to identify potential confounders for the associationbetween finasteride and male breast cancer. A logistic regression model comparedfinasteride users and nonusers with regard to potential confounders that were mea-surable in registries and population surveys.Results: Finasteride users had higher odds of testicular abnormalities (odds ratio[OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exoge-nous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabe-tes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry orin high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), liv-ing in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70;0.50-0.99) compared to nonusers.Conclusions: Systematic differences between finasteride users and nonusers werefound emphasizing the importance of confounder adjustment of associationsbetween finasteride and male breast cancer.
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6.
  • Bosetti, Cristina, et al. (author)
  • High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries
  • 2011
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 129:1, s. 173-179
  • Journal article (peer-reviewed)abstract
    • Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.
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7.
  • 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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  • Chen, Zhishan, et al. (author)
  • Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
  • 2024
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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  • Fallah, Mahdi, et al. (author)
  • Risk of thyroid cancer in first-degree relatives of patients with non-medullary thyroid cancer by histology type and age at diagnosis: a joint study from five Nordic countries
  • 2013
  • In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 50:6, s. 373-382
  • Journal article (peer-reviewed)abstract
    • Background We aimed to estimate lifetime cumulative risk of thyroid cancer (CRTC) in first-degree relatives of patients with non-medullary thyroid cancers (NMTC), including papillary (PTC)/follicular/oxyphilic/anaplastic thyroid carcinoma, by histology and age at diagnosis in patients and their relatives. Design A population-based cohort of 63 495 first-degree relatives of 11 206 NMTC patients diagnosed in 1955-2009 in Nordic countries was followed for cancer incidence. Standardised incidence ratios (SIRs) were calculated using histology-specific, age-specific, sex-specific, period-specific and country-specific incidence rates as reference. Results The 0-84-year CRTC in female relatives of a patient with PTC was 2%, representing a threefold increase over the general population risk (SIR=2.9, 95% CI 2.4 to 3.4; Men: CRTC=1%, SIR=2.5, 95% CI 1.9 to 3.3). When there were >= 2 PTC patients diagnosed at age <60 years in a family, CRTC for female relatives was 10% (male 24%). Twins had a 23-fold increased risk of concordant PTC. Family history of follicular/oxyphilic/anaplastic carcinoma increased CRTC in relatives to about 1-2%. Although no familial case of concordant oxyphilic/anaplastic carcinoma was found, familial risks of discordant histology types of NMTC were interchangeably high for most of the types, for example, higher risk of PTC when a first-degree relative had follicular (SIR=3.0, 95% CI 1.7 to 4.9) or anaplastic (SIR=3.6, 95% CI 1.2 to 8.4) carcinoma. The earlier a patient was diagnosed with PTC in a family, the higher was the SIR in his/her younger relatives. There was a tendency towards concordant age at diagnosis of thyroid cancer among relatives of PTC patients. Conclusions This study provides clinically relevant risk estimates for family members of NMTC patients.
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  • Fernandez-Rozadilla, Ceres, et al. (author)
  • Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
  • 2023
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
  • Journal article (peer-reviewed)abstract
    • Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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13.
  • 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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  • 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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  • Hill, Deirdre A., et al. (author)
  • Breast cancer risk following radiotherapy for Hodgkin lymphoma : modification by other risk factors
  • 2005
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 106:10, s. 3358-65
  • Journal article (peer-reviewed)abstract
    • The importance of genetic and other risk factors in the development of breast cancer after radiotherapy (RT) for Hodgkin lymphoma (HL) has not been determined. We analyzed data from a breast cancer case-control study (105 patients, 266 control subjects) conducted among 3 817 survivors of HL diagnosed at age 30 years or younger in 6 population-based cancer registries. Odds ratios (ORs) and excess relative risks (ERRs) were calculated using conditional regression. Women who received RT exposure (> or = 5 Gy radiation dose to the breast) had a 2.7-fold increased breast cancer risk (95% confidence interval (CI) 1.4-5.2), compared with those given less than 5 Gy. RT exposure (> or = 5 Gy) was associated with an OR of 0.8 (95% CI, 0.2-3.4) among women with a first- or second-degree family history of breast or ovarian cancer, and 5.8 (95% CI, 2.1-16.3) among all other women (interaction P = .03). History of a live birth appeared to increase the breast cancer risk associated with RT among women not treated with ovarian-damaging therapies. Breast cancer risk following RT varied little according to other factors. The additional increased relative risk of breast cancer after RT for HL is unlikely to be larger among women with a family history of breast or ovarian cancer than among other women.
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  • Holl, Katsiaryna, et al. (author)
  • Effect of long-term storage on hormone measurements in samples from pregnant women : the experience of the Finnish Maternity Cohort
  • 2008
  • In: Acta Oncologica. - Stockholm : Taylor & Francis. - 0284-186X .- 1651-226X. ; 47:3, s. 406-412
  • Journal article (peer-reviewed)abstract
    • Validity of biobank studies on hormone associated cancers depend on the extent the sample preservation is affecting the hormone measurements. We investigated the effect of long-term storage (up to 22 years) on immunoassay measurements of three groups of hormones and associated proteins: sex-steroids [estradiol, progesterone, testosterone, dihydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG)], pregnancy-specific hormones [human chorionic gonadotropin (hCG), placental growth hormone (pGH), alpha-fetoprotein (AFP)], and insulin-like growth factor (IGF) family hormones exploiting the world largest serum bank, the Finnish Maternity Cohort (FMC). Hormones of interest were analyzed in a random sample of 154 Finnish women in the median age (29.5 years, range 25 to 34 years) of their first pregnancy with serum samples drawn during the first trimester. All hormone measurements were performed using commercial enzyme-linked- or radio-immunoassays. Storage time did not correlate with serum levels of testosterone, DHEAS, hCG, pGH and total IGFBP-1. It had a weak or moderate negative correlation with serum levels of progesterone (Spearman's ranked correlation coefficient (rs)=− 0.36), IGF-I (rs=−0.23) and IGF binding protein (BP)-3 (rs=−0.38), and weak positive correlation with estradiol (rs=0.23), SHBG (rs=0.16), AFP (rs=0.20) and non-phosphorylated IGF binding protein (BP)-1 (rs=0.27). The variation of all hormone levels studied followed the kinetics reported for early pregnancy. Bench-lag time (the time between sample collection and freezing for storage) did not materially affect the serum hormone levels. In conclusion, the stored FMC serum samples can be used to study hormone-disease associations, but close matching for storage time and gestational day are necessary design components of all related biobank studies.
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  • Holl, Katsiaryna, et al. (author)
  • Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study
  • 2009
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:12, s. 2923-2928
  • Journal article (peer-reviewed)abstract
    • According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs Were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG,). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers With high androstenedione levels had ail increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay or maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (C) 2009 UICC
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  • Holl, Katsiaryna, et al. (author)
  • Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study
  • 2008
  • In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - Oxford : Wiley. - 1600-0463 .- 0903-4641. ; 116:9, s. 816-822
  • Journal article (peer-reviewed)abstract
    • During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73: 95% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age(OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.
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19.
  • Holmila, Reetta, et al. (author)
  • Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer
  • 2010
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:3, s. 578-588
  • Journal article (peer-reviewed)abstract
    • The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (Cl), 5.0-31.6]. TP53 mutations occurred in all histologies, with an overall frequency of 77%. TP53 mutation positive status was most common in adenocarcinoma (OR 2.0, 95% Cl, 1.1-3.7; compared with squamous cell carcinoma), and mutation positivity showed an overall, nonsignificant association with wood-dust exposure (OR 1.6, 95% Cl, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (>= 24 years, OR 5.1, 95% Cl, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% Cl, 1.2-10.8) and cumulative level (>= 30 mg/m(3) x years; OR 3.5, 95% Cl, 1.2-10.7) of wood-dust exposure; adjustment for formaldehyde affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.
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20.
  • Kauppila, Joonas H., et al. (author)
  • Risk Factors for Suicide After Bariatric Surgery in a Population-based Nationwide Study in Five Nordic Countries
  • 2022
  • In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 275:2, s. E410-E414
  • Journal article (peer-reviewed)abstract
    • Objective:To identify risk factors for suicide after bariatric surgery.Summary background data:Bariatric surgery reduces obesity-related mortality. However, it is for unclear reasons is associated with an increased risk of suicide.Methods:This population-based cohort study included patients having undergone bariatric surgery in 1982 to 2012 in any of the 5 Nordic countries, with follow-up through 2012. Eleven potential risk factors of suicide (sex, age, comorbidity, surgery type, surgical approach, calendar year of surgery, history of depression or anxiety, psychosis, schizophrenia, mania, or bipolar disorder, personality disorder, substance use, and number of previously documented psychiatric diagnoses) were analyzed using Cox regression.Results:Of 49,977 bariatric surgery patients, 98 (0.2%) committed suicide during follow-up. Women had a decreased risk of suicide compared to men (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.33-0.77), although age and comorbidity did not influence this risk. Compared to gastric bypass, other types of bariatric surgery had lower risk of suicide (HR = 0.44, 95%CI 0.27-0.99). There was no difference in suicide risk between laparoscopic and open surgical approach. A history of depression or anxiety (HR = 6.87, 95%CI 3.97-11.90); mania, bipolar disorder, psychosis, or schizophrenia (HR = 2.70, 95%CI 1.14-6.37); and substance use (HR = 2.28, 95%CI 1.08-4.80), increased the risk of suicide. More of the above psychiatric diagnoses increased the risk of suicide (HR = 22.59, 95%CI 12.96-39.38 for ≥2 compared to 0 diagnoses).Conclusions:Although the risk of suicide is low, psychiatric disorders, male sex, and gastric bypass procedure seem to increase the risk of suicide after bariatric surgery, indicating a role for tailored preoperative psychiatric evaluation and postoperative surveillance.
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  • Kharazmi, Elham, et al. (author)
  • Familial Risk of Small Intestinal Carcinoid and Adenocarcinoma
  • 2013
  • In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-7714 .- 1542-3565. ; 11:8, s. 944-949
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Small intestinal cancer (SIC) is rare, and its etiology is poorly understood. We compared clusters of families with SICs of different histologic subtypes. METHODS: By using the nationwide family cancer data sets of Sweden and Finland, we identified a cohort of 9964 first-degree relatives of 1799 patients with SIC, diagnosed from 1961 through 2009. Data were collected from time periods as long as 47 years (mean, 35.4 y), and cancer incidence was determined. Standardized incidence ratios (SIRs) were calculated and stratified by sex, age, time period, and cancer type, using the incidence rates for the entire national population as the reference. RESULTS: Among the 1799 SIC cases, 1.1% had a sibling with SIC, so the SIR was 11.8 (95% confidence interval [CI], 7.2-18.2); 1.1% had a parent or child with SIC (SIR, 3.5; 95% CI, 2.0-5.6). The SIR of concordant carcinoid histology of SIC among siblings was 28.4 (95% CI, 14.7-49.6; n = 12) and in parent-child pairs was 9.9 (95% CI, 5.4-16.6; n = 14). The familial risk of concordant histologic subtypes increased for siblings diagnosed with adenocarcinoma, but only 2 familial cases were identified. In family members of patients with SIC of the adenocarcinoma subtype, risks of colorectal and bladder cancer were modestly but significantly increased compared with the general population. Family members of patients with SIC of the carcinoid subtype had an increased risk for kidney cancer and polycythemia vera. CONCLUSIONS: Based on data from our population-based study, first-degree relatives of patients with small intestinal carcinoid tumors have developed these tumors with high incidence. Because of the rareness of this tumor, the absolute risk remains moderate even within families. Gastroenterologists could inform patients with small intestinal carcinoids about the familial risk and encourage counseling for their first-degree relatives. Studies are needed to identify genetic factors that affect susceptibility to SIC.
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23.
  • Kharazmi, Elham, et al. (author)
  • Familial risks for childhood acute lymphocytic leukaemia in Sweden and Finland: far exceeding the effects of known germline variants
  • 2012
  • In: British Journal of Haematology. - : Wiley. - 0007-1048. ; 159:5, s. 585-588
  • Journal article (peer-reviewed)abstract
    • Despite recent successes in the identification of genetic susceptibility loci, no familial risk has been demonstrated for childhood acute lymphoblastic leukaemia (ALL). We identified 3994 childhood ALL cases from two cancer registries; family members were obtained from population registers. The standardized incidence ratio for familial risk in singleton siblings and twins was 3.2 (95% confidence interval 1.55.9) and 162.6 (70.2320.4), respectively. The present data constitute the first demonstration of familial risk for singleton siblings; the high risk for twins is believed to result from shared prenatal blood circulation. The data suggest that currently unidentified genetic loci underlie these observed familial effects.
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24.
  • Kharazmi, Elham, et al. (author)
  • Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: A joint study from five Nordic countries.
  • 2015
  • In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 126:17, s. 1990-1995
  • Journal article (peer-reviewed)abstract
    • The rarity of familial Hodgkin lymphoma (HL) has hampered detailed analyses of familial clustering. We aimed to provide the familial risk of HL by relationship, histology, age at diagnosis and sex. A cohort of 57,475 first-degree relatives of 13,922 HL patients, diagnosed between 1955 and 2009, in five European countries was followed for HL incidence. Standardized incidence ratios (SIRs) were calculated using histology-, age-, sex-, period-, and country-specific incidence rates as the reference. The lifetime cumulative risks (CR) were also calculated. The overall CR of HL in first-degree relatives of a patient with HL was 0.6%, which represents a 3-fold (SIR=3.3, 95%CI=2.8-3.9) increased risk over the general population risk. The risk in siblings (6.0-fold; 4.8-7.4) was significantly higher than in parents/children (2.1-fold; 1.6-2.6). Very high lifetime risk of HL was found for those with multiple affected first-degree relatives (13-fold; 2.8-39) and for same-sex twins (57-fold; 21-125). We found high familial risks between some concordant histological subtypes of HL [lymphocyte-rich (81-fold, 30-177) and nodular sclerosis (4.6-fold, 2.9-7.0)] and also between some discordant subtypes. The familial risk in sisters (9.4-fold; 5.9-14) was higher than in brothers (4.5-fold; 2.9-6.7) or unlike-sex siblings (5.9-fold; 4.3-8.1). The lifetime risk of HL was higher when first-degree relatives were diagnosed at early ages (before age 30). This study provides tangible absolute risk estimates for relatives of HL patients, which can be used as a sex-, age-, and family history-based risk calculator for classical Hodgkin lymphoma by oncologists and genetic counselors.
  •  
25.
  • Koivisto-Korander, Riitta, et al. (author)
  • Second primary malignancies among women with uterine sarcoma
  • 2012
  • In: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 126:1, s. 30-35
  • Journal article (peer-reviewed)abstract
    • Objective. Uterine sarcomas (US) are rare malignancies with unclear aetiology. Studies on uterine sarcomas in the setting of second primary malignant tumours can provide clues to aetiology and identify side effects of different treatments. Methods. A cohort of 8606 cases of US was extracted from the data from 13 cancer registries and followed for second primary cancers within the period 1943-2000. Standardized incidence ratios (SIRs) were calculated, and Poisson regression analyses were performed. Results. There were 499 cancer cases observed after a first diagnosis of US (SIR 1.26, 95%CI 1.16-1.38). SIRs were elevated for cancers of the mouth and pharynx (2.16, 95%CI 1.15-3.69), colorectum (1.60, 95%CI 1.28-1.98), lung (1.73, 95%CI 1.27-2.29), breast (1.25, 95%CI 1.05-1.49), urinary bladder (1.74, 95%CI 1.02-2.79), kidney (2.00, 95%CI 1.24-3.06), thyroid gland (2.74, 95%CI 1.42-4.79), and soft tissue sarcoma (5.23, 95%CI 2.51-9.62). The risk of breast cancer increased along with increasing age of US diagnosis (p trend 0.040). The risk of kidney cancer increased along with decreasing age of US diagnosis (p trend 0.004) and short time since the US diagnosis (p trend 0.018). Conclusions. Our study demonstrated increased risk of certain cancers following a diagnosis of US. The elevated risk for breast cancer may indicate shared hormonal aetiology, while the increased risk of colorectal and bladder cancers after US may be caused by radiation therapy of US. The clustering of smoking-related cancers after US is worth exploring in the future. (c) 2012 Elsevier Inc. All rights reserved.
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