| 1. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Abril, Jazmine, et al.
(author)
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Associations between pregnancy-related factors and birth characteristics with risk of rare uterine cancer subtypes : a Nordic population-based case-control study
- 2024
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In: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 35:5, s. 741-747
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Journal article (peer-reviewed)abstract
- Purpose: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas.Methods: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined.Results: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. >= 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01).Conclusion: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies.
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| 3. |
- Bjørge, Tone, et al.
(author)
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Reproductive history and risk of colorectal adenocarcinoma in parous women : a Nordic population-based case-control study
- 2016
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:11, s. 1416-1420
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Journal article (peer-reviewed)abstract
- Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.
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| 4. |
- Daltveit, Dagrun Slettebo, et al.
(author)
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Cancer risk in the siblings of individuals with major birth defects : a large Nordic population-based case-control study
- 2023
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:6, s. 1826-1835
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Journal article (peer-reviewed)abstract
- Background: Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear.Methods: We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models.Results: In the total study population (aged 0-46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97-1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05-1.28). The overall risk of childhood cancer (0-19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00-1.19), which was mainly driven by lymphoma (1.35; 1.09-1.66), neuroblastoma (1.51; 1.11-2.05) and renal carcinoma (5.03; 1.73-14.6). The risk of cancer also increased with the number of siblings with birth defects (P-trend = 0.008).Conclusion: Overall risk of cancer among individuals (aged 0-46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0-19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors.
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| 5. |
- Daltveit, Dagrun Slettebo, et al.
(author)
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Sex differences in childhood cancer risk among children with major birth defects : a Nordic population-based nested case-control study
- 2023
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:2, s. 450-465
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Journal article (peer-reviewed)abstract
- Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0-19 years) and 218 980 matched population controls, born 1967-2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6-12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8-2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6-3.1) than males (OR = 2.1, 95% CI = 1.9-2.2, P-interaction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, P-NIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect-cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.
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| 6. |
- Kitahara, Cari M., et al.
(author)
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Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring : a Nordic population-based nested case-control study
- 2021
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In: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:2, s. 94-105
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Journal article (peer-reviewed)abstract
- Background Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified. Methods In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs. Findings Of the 2437 cases, 1967 (81.4%) had papillary carcinomas, 1880 (77.1%) were women, and 1384 (56.7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1.14 [95% CI 1.05-1.23]) and congenital hypothyroidism (4.55 [1.58-13.08]); maternal diabetes before pregnancy (OR 1.69 [0.98-2.93]) and postpartum haemorrhage (OR 1.28 [1.06-1.55]); and (from registry data in Denmark) maternal hypothyroidism (18.12 [10.52-31.20]), hyperthyroidism (11.91 [6.77-20.94]), goiter (67.36 [39.89-113.76]), and benign thyroid neoplasms (22.50 [6.93-73.06]) were each associated with an increased risk of thyroid cancer in offspring. Interpretation In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring.
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| 7. |
- Kitahara, Cari M., et al.
(author)
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Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk : A Nordic Population-Based Registry Study
- 2023
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In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 192:1, s. 70-83
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Journal article (peer-reviewed)abstract
- Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer >= 2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.
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| 8. |
- Ording, Anne Gulbech, et al.
(author)
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Birthweight and all-cause mortality after childhood and adolescent leukemia : a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State
- 2020
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In: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 59:8, s. 949-958
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Journal article (peer-reviewed)abstract
- Background: High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia. Material and methods: In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia. Results: Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (>= 4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged <= 1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8). Conclusion: This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.
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| 9. |
- Sköld, Camilla, et al.
(author)
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Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women : a registry-based study
- 2020
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 123:1, s. 161-166
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Journal article (peer-reviewed)abstract
- BackgroundNon-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear.MethodsUsing data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970–2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases’ birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs.ResultsThe risk of SCSTs, but not GCTs, decreased with higher age at last birth [≥40 versus <25 years: OR 0.48 (95% CI 0.23–0.98)]. The risk of SCSTs (but not GCTs) also decreased with shorter time since last birth. Number of births, preterm birth, preeclampsia, and offspring size were not associated with risk of SCSTs or GCTs.ConclusionsWe found a decreased risk of SCSTs with higher age at last birth and shorter time since last birth. The risk of SCSTs (but not GCTs) may be influenced by the woman’s reproductive history.
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| 10. |
- Sköld, Camilla, et al.
(author)
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Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women
- 2018
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 143:8, s. 1858-1867
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Journal article (peer-reviewed)abstract
- Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) 30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [>= 4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), p(heterogeneity)<0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.
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