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Objective To investigate if cancer in pregnancy causes a higher risk of venous thromboembolism (VTE) during pregnancy and postpartum compared with pregnant women without cancer. Design A historical prospective cohort study using data from nationwide registries. Setting and population We assessed all pregnancies in Denmark between 1 January 1977 and 31 December 2017. Methods We linked information concerning cancer diagnosis, pregnancy and VTE diagnosis and potential confounders. Event rates of VTE for women with pre-pregnancy cancer, cancer in pregnancy and without cancer were calculated per 10 000 pregnancies and compared using logistic regression analysis. Main outcome measures Occurrence of VTE during pregnancy or the postpartum period. Results A total of 3 581 214 pregnancies were included in the study and we found 1330 women with cancer in pregnancy. In pregnant women with cancer, the event rate of VTE was 75.2 per 10 000 pregnancies compared with 10.7 per 10 000 pregnancies in the no cancer group. The findings correspond to an increased adjusted odds ratio of 6.50 (95% CI3.5-12.1) in the cancer in pregnancy group in comparison with the no cancer group. Conclusions Women with cancer in pregnancy have a markedly higher risk of pregnancy-associated VTE compared with women without cancer. In pregnancy-related VTE risk assessment, the presence of cancer alone may be sufficient to indicate thromboprophylaxis. Tweetable abstract Cancer in pregnancy increases the risk of VTE during pregnancy and the postpartum period.

Introduction/Background The few studies investigating a potential association between benign ovarian tumors and endometrial cancer have been inconclusive. Using data from a large Danish register-based cohort study, we assessed the overall and type-specific risk of endometrial cancer among women with a benign ovarian tumor. Methodology We identified all Danish women diagnosed with a benign ovarian tumor during 1978–2016 in the Danish National Patient Register (n = 149,807). The study population was followed for subsequent development of endometrial cancer by linkage to the Danish Cancer Register and standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) were calculated after correction for hysterectomy. Results Women with benign ovarian tumors had a decreased incidence of endometrial cancer (SIR = 0.74, 95% CI: 0.68–0.81) compared with women in the general Danish female population. Both solid benign ovarian tumors (SIR = 0.79, 95% CI 0.70–0.88) and cystic benign ovarian tumors (SIR = 0.68, 95% CI 0.58–0.78) were associated with decreased incidences of endometrial cancer. Likewise, women with benign ovarian tumors had decreased incidences of both type I and type II endometrial cancer. The incidence of endometrial cancer was decreased to virtually the same magnitude irrespective of the age at diagnosis of a benign ovarian tumor and the reduction persisted for up to 20+ years after the ovarian tumor diagnosis. Conclusion The risk of endometrial cancer was decreased beyond the first year after a benign ovarian tumor and the decrease persisted for 20 or more years. The possible underlying mechanisms are not known and should be investigated further. Disclosures None.

Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

We examined the risk of cancer and survival in a cohort of patients hospitalised with herpes zoster between 1977 and 1996, drawn from the Danish National Registry of Patients. Through linkage with the Danish Cancer Registry, we compared the observed number of cancers with the expected number on the basis of national age-, gender-, and site-specific incidence rates. The survival of herpes zoster patients with cancer was compared with that of non-herpes zoster patients with cancer. Among the 10 588 patients hospitalised with herpes zoster whom we identified, 1427 cancers were observed compared with 1239 expected (relative risk=1.2, 95% confidence interval 1.1-1.2). The risk was substantially elevated during the first year of follow-up, mainly for haematological cancer. Patients with cancer within 1 year of follow-up had a higher prevalence of distant metastases than controls, although the mortality was similar. For those with haematological cancer, however, the mortality was higher for herpes zoster patients than for controls. Haematological cancer following hospitalisation for herpes zoster has a poorer prognosis than in non-herpes zoster patients.

There is increasing evidence of an inverse association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of colorectal cancer. However, data regarding other cancer sites are limited. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared cancer incidence among 172 057 individuals prescribed nonaspirin NSAIDs with expected incidence (based on county-specific cancer rates) during a 9-year study period. A total of 6081 incident cancer cases were diagnosed among NSAID users vs 5722 expected (standardised incidence ratio (SIR) 1.1, 95% confidence interval (CI)1.0-1.1). The SIRs for colon and rectal cancer among persons who obtained 10 or more prescriptions were 0.7 (95% CI 0.6-0.9) and 0.6 (95% CI 0.4-0.9), respectively. Similarly, reduced risk estimates were found for stomach (SIR 0.7, 95% CI 0.4-1.1) and ovarian cancer (SIR 0.7, 95% CI 0.4-1.0). Standardised incidence ratios for other cancers among those with 10 or more prescriptions tended to be close to 1.0, except for lung, kidney, and prostate cancers with SIRs of 1.3 (95% CI 1.1-1.6), 1.4 (95% CI 0.9-2.1), and 1.6 (95% CI 1.3-2.0), respectively. We found protective associations of NSAIDs against colon, rectal, stomach, and ovarian cancer. Reasons for the increased risk for some cancer sites are not clear.

Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found.

Objective: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. Methods: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977–1993; Sweden 1965–1993) were linked to tumor registry data for up to 15–28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. Results: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5, 95% CI = 1.3–1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.6–2.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2–17.4), colon (SIR = 2.6, 95% CI = 1.6–3.8), and rectum (SIR = 2.5, 95% CI = 1.3–4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI = 1.2–5.0), thyroid (SIR = 3.7, 95% CI = 1.8–10.9), kidney (SIR = 3.2, 95% CI = 1.6–5.5), and bone (SIR = 13.8, 95% CI = 1.7–50.0). Conclusions: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-1 system in the etiology of various cancers.

Objectives– To investigate the risk of neurological disease among women with cosmetic breast implants. Material and methods– We identified 1653 women who had undergone breast implant surgery at private clinics in Denmark and a comparison cohort of 1736 women who underwent other types of cosmetic surgery at the same clinics. Ratios of observed-to-expected numbers of hospitalizations for neurological disease in the private implant and comparison cohorts were calculated, separately and combined with data from updated public hospital cohorts. Results– The occurrence of neurological disease in the private clinic implant cohort was comparable to that in the general population. A similar risk pattern was observed in the private clinic comparison cohort. When data for these private clinic cohorts were combined with updated data for public hospital cohorts, excess risks for neurological disorders were seen in both implant and comparison cohorts, reaching statistical significance only in the comparison cohort. Conclusion– Our findings indicate no causal association between silicone breast implants and neurological disease.

Objective: To increase the knowledge of the long-term effects of artificial hip and knee joint implants. Methods: The study groups consisted of 24,636 patients with osteoarthritis who underwent hip implant surgery and 5,221 who received knee implants during 1977-89. The post-implant rate of hospitalization for connective tissue disease (CTD) was compared with the rate in the general population of Denmark and with that among osteoarthritis patients without implant surgery. Results: The rates of hospitalization for CTD were higher than the background level among both hip and knee implant patients with osteoarthritis, whereas the comparison with non-implanted osteoarthritis patients revealed that the hospitalization rate for CTD was reduced after hip implant surgery, but increased after knee implant surgery. Conclusion: Since the materials used in hip and knee implants in Denmark are not substantially different, these results are unlikely to reflect an implant effect but rather the selection criteria of refe...

Many different aetiologies for childhood cancer have been suggested, but few are well established. One is that parental autoimmune disease is linked with susceptibility for haematopoietic malignancies in their offspring during childhood. The present study is the first to investigate this hypothesis using a follow-up design. A cohort of 53 811 children of more than 36 000 patients diagnosed with a systemic, organ-specific or suspected autoimmune disease were followed up for cancer incidence in the Danish Cancer Registry during 1968–1993. The parents were identified through the National Registry of Patients, while their children were traced in the Central Population Register. Cancer incidence among the offspring was compared with that in the corresponding childhood population of Denmark. In total, 115 cancers were observed among children aged 0–19 years, yielding a non-significant standardized incidence ratio of 1.07. Lymphomas contributed 21 cases to the overall number of tumours, 60% more than expected (95% confidence interval (CI) 1.0–2.4); leukaemia contributed 37 cases representing an excess of 30% (95% CI 0.9–1.8). Our results give some support to the hypothesis that parental autoimmune disease is associated with childhood lymphoma and leukaemia. © 2000 Cancer Research Campaign

To examine the association between gallstones and cholecystectomy, we conducted a nationwide population-based cohort study in Denmark. Patients with a discharge diagnosis of gallstones from 1977 to 1989 were identified from the Danish National Registry of Patients and followed up for cancer occurrence until death or the end of 1993 by record linkage to the Danish Cancer Registry. Included in the cohort were 60 176 patients, with 471 450 person–years of follow-up. Cancer risks were estimated by standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) stratified by years of follow-up and by cholecystectomy status. Among patients without cholecystectomy, the risks at 5 or more years of follow-up were significantly elevated for cancers of liver (SIR = 2.0, CI = 1.2–3.1) and gallbladder (SIR = 2.7, CI = 1.5–4.4) and near unity for cancers of extrahepatic bile duct (SIR = 1.1), ampulla of Vater (SIR = 1.0) and pancreas (SIR = 1.1). The excess risk of liver cancer was seen only among patients with a history of hepatic disease. Among cholecystectomy patients, the risks at 5 or more years of follow-up declined for cancers of liver (SIR = 1.1) and extrahepatic bile duct (SIR = 0.7), but were elevated for cancers of ampulla of Vater (SIR = 2.0, CI = 1.0–3.7) and pancreas (SIR = 1.3, CI = 1.1–1.6). These findings confirm that gallstone disease increases the risk of gallbladder cancer, whereas cholecystectomy appears to increase the risk of cancers of ampulla of Vater and pancreas. Further research is needed to clarify the carcinogenic risks associated with gallstones and cholecystectomy and to define the mechanisms involved. © 1999 Cancer Research Campaign

Objectives: It has been suggested that inflammatory bowel disease (IBD) and colon cancer are associated because they have genetic susceptibility in common, rather than IBD causing cancer. We examined the risk of colorectal cancer in first-degree relatives of patients with IBD in order to evaluate if they share the same genetic susceptibility.

To investigate the possible association between condylomata acuminata and anogenital neoplasia, a cohort of 9552 women recorded as having condylomata acuminata in the Danish Hospital Discharge Register during 1977-1989 was followed through 1991 for the occurrence of cancer and cervical intraepithelial neoplasia grade III (CIN III) by linkage to the Danish Cancer Registry. Eleven cases of vulvar cancer were identified, with 0.3 expected (standardized incidence ratio [SIR], 40.1; 95% confidence interval [CI], 20.0-71.7), and there were increased risks for cervical cancer (SIR, 2.0; 95% CI, 1.3-3.0), anal cancer (SIR, 8.5; 95% CI, 0.9-30.5), and CIN III (SIR, 2.6; 95% CI, 2.3-2.9). Risks were also elevated for non-anogenital cancers, notably lung cancer (SIR, 3.8; 95% CI, 2.2-6.0). Although confounding by smoking and other factors may exist, these results support the view that condylomata acuminata are associated with an increased risk of anogenital neoplasias, particularly vulvar cancer, and emphasize that women hospitalized with these lesions should undergo thorough anal and gynecologic examinations at regular intervals.

BACKGROUND: The occurrence of gall stones has repeatedly been associated with an increased risk for cancer of the colon, but risk associated with cholecystectomy remains unclear. AIMS: To evaluate the hypothesis in a nationwide cohort of more than 40,000 gall stone patients with complete follow up including information of cholecystectomy and obesity. PATIENTS: In the population based study described here, 42,098 patients with gall stones in 1977-1989 were identified in the Danish Hospital Discharge Register. METHODS: These patients were linked to the Danish Cancer Registry to assess their risks for colorectal and other cancers during follow up to the end of 1992. RESULTS: The analysis showed a modest increase in the number of cancers at all sites combined (n = 3940; RR, 1.07; 95% confidence intervals (CI), 1.0 to 1.1). A weak association was found for cancer of the colon (n = 360; RR, 1.09; 95% CI 1.0 to 1.2), which remained unchanged when analysed by sex, anatomical subsite, and duration of follow up. Multivariate analysis with adjustment for cholecystectomy and clinically defined obesity did not change these estimates to any significant extent. Excess risks were found for cancers of the pancreas and the small intestine. A non-significant increased risk for breast cancer was seen in women five years after initial discharge for gall stones. CONCLUSION: A borderline significant association was seen between gall stones and cancer of the colon, and for cancer of pancreas and small intestine as well as for breast cancer in women.

A cohort of 5072 patients with pernicious anaemia was identified in the Danish Hospital Discharge Register from 1977 to 1989 and, through linkage to the Danish Cancer Registry, the occurrence of cancer in the cohort was determined up to 1991. Observed numbers of cancer cases during 1-15 years of follow-up were compared with expected numbers based on national incidence rates. Besides the well-established increased risk for stomach cancer, the analysis also revealed a 2-fold increase in the relative risk for cancer of the buccal cavity and pharynx among pernicious anaemia patients in accordance with previous studies; previously reported elevated risks for other digestive tract cancers were not confirmed. There was a non-significantly increased risk for lymphatic and haematological malignancy but the risk tended to disappear after 5 years of follow-up, indicating a possible selection bias. Decreased risks for cervical cancer and non-melanoma skin cancer were also seen.

Purpose Infections have been hypothesized to be a risk factor for Hodgkin disease and non-Hodgkin lymphoma. Because infections usually occur seasonally, the authors looked at the seasonal pattern of occurrence of these diseases, since seasonal variation in occurrence would lend support to the hypothesis of an etiologic link between infection and lymphoma. Methods The authors identified 575 patients with Hodgkin disease and 498 with non-Hodgkin lymphoma under the age of 20 years in the Danish Cancer Registry from 1943 to 1994. A periodic regression model was used to evaluate the seasonal distribution of month of diagnosis and month of birth. Results For the month of diagnosis of Hodgkin disease, the peak month of occurrence was March. The peak-to-trough ratio (the estimated incidence in the month of the peak divided by the estimated incidence in the month of the trough) was 1.57. For birth date, the ratio of case births at the peak month to case births at the trough month was 1.21, with a peak in July. There was no meaningful seasonal variation in the diagnosis or month of birth of children with non-Hodgkin lymphoma. Conclusions These data corroborate a previously reported March peak in the diagnosis of Hodgkin disease.

Objective: To investigate the risk of neurologic disease among women with silicone breast implants. Background: Since 1992, several case series reported an association between silicone breast implants and neurologic diseases. Methods: Between 1977 and 1992, 1,135 women received cosmetic silicone breast implants, and 7,071 women had breast reduction surgery, as identified by the Danish National Register of Patients (NRP). NRP files provided information on numbers and types of subsequent neurologic disorders at hospital discharge, which were compared with expected numbers, calculated on the basis of national hospital discharge rates. Results: In the two study cohorts, hospital discharge rates for neurologic diseases were raised by some 60% to 70% compared with Danish women in general. Among women with silicone breast implants, 13 subsequently developed a neurologic disorder compared with 7.7 expected; whereas in the comparison group, 63 observed versus 39.1 expected disorders were recorded. These results indicate that relative to the comparison cohort, women with implants had no excessive levels of definite neurologic disease. Furthermore, medical record reviews revealed that the majority of women with implants discharged with a neurologic diagnosis had either symptoms before implant surgery or neurologic symptoms secondary to degenerative diseases. Conclusions: Our findings do not support the hypothesis of silicone-induced neurologic disease. The reasons for the elevated rates of neurologic disease in both the exposed and comparison cohorts remain unclear, but may reflect selection processes associated with these women seeking medical care more often than the general population.