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Glimelius, Ingrid
Publications (10 of 45) Show all publications
Gholiha, A. R., Hollander, P., Hedström, G., Sundström, C., Molin, D., Smedby, K. E., . . . Enblad, G. (2019). High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms. British Journal of Haematology, 184(2), 192-201
Open this publication in new window or tab >>High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms
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2019 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, no 2, p. 192-201Article in journal (Refereed) Published
Abstract [en]

Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti-CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell-infiltration was associated with the presence of B-symptoms (P = 0·028) and advanced stage, IIB-IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event-free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour-associated plasma cells in cHL reflect an important component in the microenvironment of cHL.

Keywords
CD138 plasma cells, Hodgkin's lymphoma, IgG4-producing plasma cells, Syndecan-1, tumour microenvironment
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-372809 (URN)10.1111/bjh.15703 (DOI)000455218700009 ()30506671 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-02-04Bibliographically approved
Hollander, P., Rostgaard, K., Ekström-Smedby, K., Molin, D., Loskog, A., de Nully Brown, P., . . . Glimelius, I. (2018). An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome. European Journal of Haematology, 100(1), 88-97
Open this publication in new window or tab >>An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome
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2018 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 100, no 1, p. 88-97Article in journal (Refereed) Published
Abstract [en]

Objective: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows anongoing inflammatory response consisting of varying degrees of infiltrating eosinophils,mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.

Methods: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.

Results: The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barrvirus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.

Conclusions: Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.

Keywords
Hodgkin lymphoma, Regulatory T lymphocytes, Tumor microenvironment
National Category
Cancer and Oncology
Research subject
Pathology; Oncology
Identifiers
urn:nbn:se:uu:diva-335491 (URN)10.1111/ejh.12987 (DOI)000418451500012 ()29064587 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/440, CAN 2016/607, CAN 2016/552
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2018-01-29Bibliographically approved
Weibull, C. E., Johansson, A. L., Eloranta, S., Smedby, K. E., Björkholm, M., Lambert, P. C., . . . Glimelius, I. (2018). Contemporarily Treated Patients With Hodgkin Lymphoma Have Childbearing Potential in Line With Matched Comparators. Journal of Clinical Oncology, 36(26), 2718-2725
Open this publication in new window or tab >>Contemporarily Treated Patients With Hodgkin Lymphoma Have Childbearing Potential in Line With Matched Comparators
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2018 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 26, p. 2718-2725Article in journal (Refereed) Published
Abstract [en]

Purpose With excellent cure rates for young patients with Hodgkin lymphoma (HL), there is an increasing number of female survivors of HL interested in becoming pregnant. Here, we report childbearing among contemporarily treated HL survivors in comparison with the general population. Material and Methods Using Swedish registers, 449 women (ages 18 to 40 years) diagnosed with HL between 1992 and 2009 and in remission 9 months after diagnosis were identified. Patients were age- and calendar-year-matched to 2,210 population comparators. Rates of first postdiagnosis childbirth were calculated. Hazard ratios (HRs) with 95% CIs were estimated for different follow-up periods using Cox regression. Cumulative probabilities of first childbirth were calculated in the presence of the competing risk of death or relapse. Results Twenty-two percent of relapse-free patients with HL had a child during follow-up, and first childbirth rates increased over time, from 40.2 per 1,000 person-years (1992 to 1997) to 69.7 per 1,000 person-years (2004 to 2009). For comparators, childbirth rates remained stable (70.1 per 1,000 person-years). Patients diagnosed between 2004 and 2009 had a cumulative probability of childbirth similar to comparators. Three years or more after diagnosis, no differences in childbirth rates were observed between patients and comparators, regardless of stage or treatment. Patients who received six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone had a lower childbirth rate than comparators during the first 3 years (HR, 0.23; 95% CI, 0.06 to 0.94), as did patients who received six to eight courses of chemotherapy and radiotherapy (HR, 0.21; 95% CI, 0.07 to 0.65). Conclusion Childbearing potential among female survivors of HL has improved over time, and childbirth rates 3 years after diagnosis in contemporarily treated patients are, in the absence of relapse, similar to those in the general population, regardless of stage and treatment.

Place, publisher, year, edition, pages
American Society of Clinical Oncology, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-356537 (URN)10.1200/JCO.2018.78.3514 (DOI)000445669600008 ()30044694 (PubMedID)
Funder
Swedish Cancer Society, CAN2016/803 CAN 2016/440 CAN 2015/292
Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-10-22Bibliographically approved
Hollander, P., Amini, R.-M., Ginman, B., Molin, D., Enblad, G. & Glimelius, I. (2018). Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma. PLoS ONE, 13(9), Article ID e0204870.
Open this publication in new window or tab >>Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0204870Article in journal (Refereed) Published
Abstract [en]

High expression of programmed death receptor 1 (PD-1) and its ligand (PD-L1) by leukocytes in primary classical Hodgkin lymphoma (cHL) is associated with inferior outcome. However, it is unclear how expression varies during disease progression, and in the event of relapse. Our aim was to study PD-1 and PD-L1 in consecutive biopsies from untreated and treated cHL patients. We screened pathology registries from 3500 cHL patients. Eleven patients had a diagnostic cHL biopsy and a previous benign lymph node biopsy reclassified as cHL when reviewed and designated as the untreated. Thirty patients had a primary and a relapse biopsy, designated as the treated. Biopsies were immunostained to detect PD-1+ and PD-L1+ leukocytes, and PD-L1+ tumor cells. In the untreated, none of the markers were statistically significantly different when biopsies 1 and 2 were compared. In the treated, 19, 22, and 18 of 30 cases had increased proportions of PD-1+ leukocytes, PD-L1+ leukocytes and PD-L1+ tumor cells, respectively, and were all statistically significantly increased when primary and relapse biopsies were compared. PD-1 and PD-L1 most likely increase due to primary treatment with chemotherapy and radiotherapy, which could have implications regarding treatment with PD-1 inhibitors.

National Category
Cancer and Oncology
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372644 (URN)10.1371/journal.pone.0204870 (DOI)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-16Bibliographically approved
Björkholm, M., Weibull, C. E., Eloranta, S., Smedby, K. E., Glimelius, I. & Dickman, P. W. (2018). Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma: A population-based study from Sweden. European Journal of Haematology, 101(1), 106-114
Open this publication in new window or tab >>Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma: A population-based study from Sweden
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2018 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 101, no 1, p. 106-114Article in journal (Refereed) Published
Abstract [en]

Objective: Forty percent of Hodgkin lymphoma (HL) patients are older than 50years at diagnosis, a fact which is not commonly recognized. Older patients do significantly worse than younger patients and are rarely included in clinical trials.

Methods: Using data from Swedish Cancer and Lymphoma Registries, we estimated relative survival ratios (RSRs) for 7997 HL patients (diagnosed 1973-2013; 45% 50years).

Results: The 1-year RSRs (95% confidence interval; CI) for males aged 45-59, 60-69, 70-80, and 81years and over, diagnosed in 2013, were 0.95 (0.91-0.97), 0.88 (0.81-0.92), 0.74 (0.63-0.81), and 0.52 (0.35-0.67), respectively. The corresponding 1-year RSRs for females were 0.97 (0.94-0.98), 0.91 (0.85-0.95), 0.82 (0.73-0.88), and 0.66 (0.50-0.77). No improvements in 1-year of 5-year relative survival from 2000 to 2013 were observed for patients aged 45-59 or 60-69 but there were modest improvements for patients aged 70years and older. Importantly, we saw no changes in the distribution of disease or patient characteristics between 2000 and 2013.

Conclusions: Elderly patients constitute a large group with clearly unmet medical needs. Our findings motivate a more active approach to including elderly patients in clinical trials. Our study provides a baseline for outcome comparison after the broader introduction of targeted drugs.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
elderly, Hodgkin lymphoma, relative survival, temporal trends
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-358265 (URN)10.1111/ejh.13090 (DOI)000435935800012 ()29727497 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyStockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2018-08-27 Created: 2018-08-27 Last updated: 2018-08-27Bibliographically approved
Englund, A., Glimelius, I., Rostgaard, K., Smedby, K. E., Eloranta, S., Molin, D., . . . Hjalgrim, L. L. (2018). Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.. Acta Oncologica, 57(2), 276-282
Open this publication in new window or tab >>Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 276-282Article in journal (Refereed) Published
Abstract [en]

Background: Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain.

Material and methods: We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0–24 years diagnosed in Denmark (1990–2010) and Sweden (1992–2009) in pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n = 757). Distribution of clinical characteristics was assessed with Pearson’s chi2-test and Mantel–Haenszel trend test. The Kaplan–Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression.

Results: Children (0–9 years) less often presented with advanced disease than adolescents (10–17 years) and young adults (18–24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p < .005). No variation in overall survival (OS) was seen between pediatric and adult departments or by country. Danish pediatric patients received radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p < .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric patients (0–14 years) (0.79; 95% confidence interval (CI) 0.70–0.86) than among Swedish pediatric patients (0–17 years) (0.88; 95% CI 0.83–0.92), HR (1.93; 95% CI 1.08–3.46). A similar pattern was seen between adult patients in the two countries: Denmark 10-year EFS 0.85 (95% CI 0.81–0.88), Sweden 0.88 (95% CI 0.84–0.91), adjusted HR 1.51 (95% CI 1.03–2.22).

Conclusion: Adolescents and young adults shared similar clinical presentation suggesting a rationale of harmonized treatment for these groups. Both adult and pediatric protocols provided high OS with no significant difference between the departments. The less frequent use of radiotherapy in Danish pediatric patients corresponded to a lower EFS, but comparable OS in all groups confirmed effective rescue strategies for the relapsing patients.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-343244 (URN)10.1080/0284186X.2017.1355563 (DOI)000423473200016 ()28760045 (PubMedID)
Funder
Swedish Childhood Cancer Foundation, KF2014-0003; FTJH11/002Swedish Cancer Society, 2012/774; 2016/440
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-03-09Bibliographically approved
Troisi, R., Ording, A. G., Grotmol, T., Glimelius, I., Engeland, A., Gissler, M., . . . Bjorge, T. (2018). Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population-based case-control study. International Journal of Cancer, 143(8), 1904-1913
Open this publication in new window or tab >>Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population-based case-control study
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 8, p. 1904-1913Article in journal (Refereed) Published
Abstract [en]

Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population-based case-control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967-2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78-0.97), gestational hypertension (OR 0.90; 95% CI 0.86-0.93) and preeclampsia (OR 0.91; 95% CI 0.88-0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98-1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
breast cancer, Nordic countries, pregnancy, preeclampsia, hypertension
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-364128 (URN)10.1002/ijc.31600 (DOI)000443942800009 ()29752724 (PubMedID)
Funder
Novo NordiskSwedish Society for Medical Research (SSMF)Swedish Society of Medicine
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved
Sköld, C., Bjorge, T., Ekbom, A., Engeland, A., Gissler, M., Grotmol, T., . . . Glimelius, I. (2018). Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women. International Journal of Cancer, 143(8), 1858-1867
Open this publication in new window or tab >>Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 8, p. 1858-1867Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-364126 (URN)10.1002/ijc.31581 (DOI)000443942800004 ()29737528 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved
Chen, L., Eloranta, S., Martling, A., Glimelius, I., Neovius, M., Glimelius, B. & Smedby, K. E. (2018). Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register. Radiotherapy and Oncology, 126(3), 424-430
Open this publication in new window or tab >>Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register
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2018 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 126, no 3, p. 424-430Article in journal (Refereed) Published
Abstract [en]

Aim: A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). Methods: We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. Results: We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (lRR(register) = 1.41, 95% CI 1.15-2.72; IRRtrials = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR6 (months) = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Discussion: Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. (C) 2017 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2018
Keywords
Rectal cancer, Radiotherapy, Population-based cohorts, Randomized controlled trials, Long-term cardiovascular disease, Venous thromboembolism
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-352739 (URN)10.1016/j.radonc.2017.12.008 (DOI)000429762700006 ()29306497 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2018-06-07Bibliographically approved
Troisi, R., Bjorge, T., Gissler, M., Grotmol, T., Kitahara, C. M., Saether, S. M., . . . Glimelius, I. (2018). The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence. Journal of Internal Medicine, 283(5), 430-445
Open this publication in new window or tab >>The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence
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2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 5, p. 430-445Article in journal (Refereed) Published
Abstract [en]

An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy related exposures influence foetal growth cell division and organ functioning and may have a longlasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial and possibly pancreatic cancer, whilst the risk of kidney cancer is elevated in parous compared with nulliparous women. For breast, endometrial and ovarian cancer, each pregnancy provides an additional risk reduction. The associations of parity with thyroid and colorectal cancers are uncertain. The timing of reproductive events is also recognized to be important. Older age at first birth is associated with an increased risk of breast cancer, and older age at last birth is associated with a reduced risk of endometrial cancer. The risks of breast and endometrial cancers increase with younger age at menarche and older age at menopause. The mechanisms, and hormone profiles, that underlie alterations in maternal cancer risk are not fully understood and may differ by malignancy. Linking health registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal aetiology and those with less established relationships. The tendency for women to have fewer pregnancies and at later ages, together with the age-dependent increase in the incidence of most malignancies, is expected to affect the incidence of pregnancy-associated cancer.

Keywords
breast cancer, colorectal cancer, endometrial cancer, Nordic registries, ovarian cancer, Pregnancy
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-355465 (URN)10.1111/joim.12747 (DOI)000430468100002 ()29476569 (PubMedID)
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-06-29Bibliographically approved
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