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BACKGROUND: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition.METHODS: Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI RESULTS: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women.CONCLUSION: These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk.

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.

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.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.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 = 1.62.7), 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).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-I system in the etiology of various cancers.

A recent observational study suggested that the use of angiotensin-converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark.Using data from the population-based Prescription Database of North Jutland County and the Danish Cancer Registry, cancer incidence among 17,897 individuals prescribed ACE inhibitors was compared with expected incidence based on county specific cancer rates during an 8-year study period with a mean follow-up of 3.7 years. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. In addition, the authors performed a direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers (n = 47,579 individuals) by means of a Cox proportional hazards model.Overall, 909 cancer cases were observed among users of ACE inhibitors, with 846 expected based on general population rates, yielding an SIR of 1.07 (95% CI, 1.01-1.15). No risk reductions were observed for cancers of the breast and female reproductive tract, whereas nonsignificantly decreased SIRs were observed for cancers of the esophagus, stomach, and liver. Cancer of the kidney was found in significant excess (SIR, 1.6; 95% CI, 1.1-2.2). Stratification by duration of follow-up or number of prescriptions revealed no apparent trends, except for a tendency toward decreasing risk with increasing length of follow-up for smoking-related cancers. The direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers yielded results comparable to those derived from the comparison with the general population, with a hazard ratio for cancer overall of 1.01 (95% CI, 0.93-1.09).This large, population-based cohort study did not confirm a protective effect of ACE inhibitors on the development of cancer. The excess of kidney cancer observed likely reflects a correlation between hypertension and kidney cancer. Further investigation is needed to evaluate the long-term effects of ACE inhibitors beyond the observation period of this and previous studies. Also, the suggestive evidence of decreased risks for upper digestive system cancers and for smoking-related cancers over time may warrant additional investigation.

We investigated the relationship between infections with Neisseria gonorrhoeae and anogenital and other cancers.Nationwide and population based register linkage study utilizing prospectively notified information. The observed numbers of cancers among the women were compared with those expected on the basis of national incidence rates.In a cohort of 4440 women hospitalized for gonorrhea we observed a total of 227 cases of cervical intraepithelial neoplasia grade III (CIN III), with 103 expected (standardized incidence ratio (SIR), 2.2; 95% confidence interval (CI), 1.9-2.5). No significantly increased risk for other anogenital cancers or cancer at other sites was seen.These results support the view that the observed association between gonorrheal infection and subsequent cervical preneoplasia is due mainly to surveillance bias. However, our results also indicate that women hospitalized with a N. gonorrhoeae infection will benefit from the compliance with the regular Pap smear screening programs.

Energy restriction reduces the incidence of malignant tumors in experimental animals, but evidence for a similar effect in humans is lacking. To test the hypothesis in humans, we investigated cancer incidence among patients with anorexia nervosa, who have had an extremely low intake of calories for prolonged periods of their lives.Patients with anorexia nervosa (2151 women and 186 men) during 1970-1993 were identified in the population-based Danish Psychiatric Case Register and the National Registry of Patients. The cohort was linked to the Danish Cancer Registry, and cancer incidence among cohort members was compared with that of the general population.The overall cancer incidence among women with anorexia nervosa was reduced by a factor of 0.80 (95% confidence interval 0.52-1.18) below that of the general population on the basis of 25 observed and 31.4 expected cases. Among men, two cases of cancer were observed, both confined to the brain, whereas 0.2 cases were expected.The finding of a slight reduction in cancer risk among women with anorexia nervosa may support the theory that a low-energy diet may decrease tumor development in humans. However, longer follow-up and control for confounding factors are needed to obtain more convincing evidence.

To investigate the risk of neurological disease among women with cosmetic breast implants.We identified 1,653 women who had undergone breast implant surgery at private clinics in Denmark and a comparison cohort of 1,736 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.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.Our findings indicate no causal association between silicone breast implants and neurological disease.

Most studies on cancer incidence after breast implantation have focused on breast cancer, while the risk of cancers at other sites has been less well investigated. We examined cancer incidence among 1,653 women who underwent cosmetic breast implant surgery at private clinics of plastic surgery in Denmark and 1,736 women attending the same clinics for other reasons during the period 1973-1995. Furthermore, we updated previously reported results among 1,114 women who received implants for cosmetic indications at public hospitals. All women were followed for cancer through the Danish Cancer Registry. In comparison with the general female population, the overall standardized incidence ratio (SIR) for cancer among women who received implants in private clinics was 1.65 [95% confidence interval (CI) = 1.17-2.27]. This elevated SIR reflected increased incidence ratios for almost all major cancer sites; however, only for non-melanoma skin cancer was there an excess of more than 2 cases. No significant excess of cancer was observed among women who received implants in public hospitals (SIR = 1.10, 95% CI = 0.76-1.52) or among women attending the private clinics for other problems (SIR = 1.10, 95% CI = 0.78-1.52). The SIRs for breast cancer after breast implantation were 1.1 (95% CI = 0.5-2.2) among private clinic patients and 0.9 (95% CI = 0.4-1.7) among public hospital patients. The overall findings of these 2 implant cohorts and results from other investigations suggest that cancer risk is probably not increased among women receiving cosmetic breast implants. The inconsistent results for private clinics and public hospitals are likely related to selection bias and confounding among the private clinic patients, but our data did not permit exploration of these possibilities. Further research into the determinants of these inconsistencies is warranted.

Data regarding the association between the use of calcium channel blockers and cancer risk have been conflicting. In the current study, the authors examined the cancer risk and mortality in users of calcium channel blockers in North Jutland County, Denmark.The authors conducted a cohort study using record linkage between a population-based prescription database, the Danish Cancer Registry, and the Danish Death Registry including 23, 167 users of calcium channel blockers who received/=2 prescriptions between January 1, 1989 and December 31, 1995. The authors calculated the standardized incidence ratios and standard mortality ratios for cancer, along with corresponding 95% confidence intervals (95% CI).Overall, 967 incident cases of cancer occurred, resulting in a standardized incidence ratio of 1.04 (95% CI, 0.98-1.11). There was a slightly elevated nonsignificant risk of tobacco-related cancer. No increased risk of breast or colon carcinoma was observed. The cancer mortality was close to that expected in the background population (standardized mortality ratio of 0.97; 95% CI, 0.89-1.04).This large-scale, population-based cohort study adds to the increasing evidence indicating no substantial association between the use of calcium channel blockers and the incidence rate of cancer or cancer mortality.

The large number of studies of intestinal cancer among patients with Crohn's disease have provided inconsistent risk estimates in regard to risk of both colorectal and small intestinal cancer. We investigated incidence of cancer among Crohn's disease patients in comparison with the incidence in the general population of Denmark.From the Danish National Registry of Patients we identified 2645 patients who had been hospitalized with Crohn's disease during 1977-1989. Cancer incidence for up to 17 years was determined in the cohort and compared to an expected number derived from national cancer incidence rates.The 15 observed cases of colorectal cancer were close to the expected number of 13.1 (SIR = 1.1; 95% CI 0.6-1.9), whereas the five cases of small intestinal cancer (three adenocarcinomas and two carcinoids) observed corresponded to an 18-fold increased risk (SIR = 17.9; 95% CI 5.8-42).A potential excess of colorectal cancer among subgroups of patients with Crohn's disease was not detectable in the overall risk estimate for colorectal cancer. Only for small intestinal cancer was a significantly elevated risk found among these patients hospitalized with Crohn's disease.

To assess the cancer risk of monoclonal gammopathy of undetermined significance (MGUS) we identified 1229 cases of MGUS in the period 1978 to 1993. Data on cancer occurrence in the MGUS cohort were obtained from the Danish Cancer Registry. The expected numbers of cancer cases were calculated from age-, sex-, county-, and period-specific cancer incidence rates. In the MGUS cohort 64 new cancers with a known association with M-components were diagnosed versus 5.0 expected giving a standardized incidence ratio (SIR) of 12.9 (95% confidence interval, 9.9-16.5). The relative risks of developing multiple myeloma (SIR 34.3), Waldenström's macroglobulinemia (SIR 63.8), and non-Hodgkin's lymphoma (SIR 5.9) were significantly increased and independent of time passed from detection of the M-component. The relative risk of chronic lymphocytic leukemia was not significantly increased, SIR 2.7 (0.5-7. 7). Among cancer sites without known association with M-components 141 cases were observed versus 94.6 expected giving a SIR of 1.5 (1. 3-1.8). This enhanced risk was seen for several non-hematological cancer sites but for most cancer sites the risk was dependent on time passed from detection of the M-component, indicating a bias rather than a causal role of MGUS.

A nationwide cohort study of hip and knee replacement patients in Denmark was undertaken to assess any carcinogenic potential of these implants. A cohort of 22,997 osteoarthritis patients who received hip replacements and of 4,771 osteoarthritis patients who received knee replacements during the period 1977 through 1989 were identified using the nationwide Danish Hospital Discharge Registry. These patients were followed for cancer occurrence through 1993, using the Danish Cancer Registry. There was no overall excess of cancer in either the hip implant cohort [standardized incidence ratio (SIR) = 0.94; 95% confidence interval (CI)= 0.91-0.98] or the knee implant cohort (SIR = 0.97; 95% CI = 0.89-1.06). The risk reduction in both groups of patients reflected for the most part reduced risks for cancers of the respiratory system and the digestive tract, particularly stomach cancer (SIR = 0.69; 95% CI = 0.50-0.81 for hip replacement patients; SIR = 0.46; 95% CI = 0.20-0.91 for knee replacement patients). Elevated risks were observed for melanoma of the skin in both groups of patients. There was no clear excess risk for lymphohematopoietic cancers or malignant neoplasms of the bone or connective tissue among implant patients in either implant group. Contrary to an earlier study in Sweden, we did not find an excess risk for kidney or prostate cancers. In summary, these nationwide results indicate no overall cancer hazard among hip and knee implant patients, but limited follow-up warrants continued surveillance of individuals undergoing these increasingly common surgical procedures.

The use of artificial joint implants has risen greatly over the past years. However, few investigations of the cancer risk associated with implants have been performed. We investigated cancer risk in patients with finger and hand joint and temporo-mandibular (TMJ) joint implants. A nationwide cohort in Denmark of patients with finger and hand joint prostheses (n = 858) or TMJ implants (n = 389) was followed from January 1, 1977, to December 31, 1995, to evaluate any potential cancer risks subsequent to receiving these implants. Standardized incidence ratios (SIRs) for all cancers were 1.0 (95% CI = 0.8-1.2) for the finger and hand joint cohort and 1.1 (95% CI = 0.8-1.7) for the TMJ cohort. A significant risk for non-Hodgkin's lymphoma was found in the finger and hand joint cohort (SIR = 3.8, 95% CI = 1.5-7.8). When the finger and hand joint cohort was stratified by diagnosis of rheumatoid arthritis, the excess risk was seen only in the group with rheumatoid arthritis. This is consistent with past studies, which have found an association between rheumatoid arthritis and non-Hodgkin's lymphoma. Our results provide evidence that the cancer risk for patients with finger and hand joint prostheses and TMJ implants is similar to that for the general population.

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.We identified patients with IBD in the Danish Hospital Discharge Registry. A cohort of all first-degree relatives to these patients were linked to the Danish Cancer Registry. Colorectal cancers observed were compared with expected values based on age, gender, and calendar-specific incidence rates in the general population.Among 4,496 patients with IBD, a total of 19,645 relatives were identified. For parents of patients with Crohn's disease, we observed 19 cases of colorectal cancer compared with 20 expected (standardized incidence ratio [SIR] = 1.0, 95 percent confidence interval [CI] = 0.6-1.5). For parents of patients with ulcerative colitis, 55 cases were observed compared with 51 expected (SIR = 1.1, CI = 0.8-1.4).The study did not corroborate the hypothesis that the same genetic factors play a significant role in the etiology of colorectal cancer and IBD, but more information is needed to disregard the possible link between IBD and colon cancer.

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.

Epidemiologic studies have not been able definitely to exclude that appendectomy carries a cancer risk. This study was conducted to clarify whether appendectomy is associated with a subsequent increase in cancer risk, since appendectomy is frequently an elective procedure.The present study included more than 82,000 persons who underwent appendectomy for acute appendicitis during 1977-89 according to the nation-wide Danish Hospital Discharge Register. During a follow-up interval of up to 17 years, cancer incidence was assessed by linkage to the Danish Cancer Registry and compared with the incidence in the general population of Denmark.The total number of malignancies among appendectomized persons was 1.05 times higher than expected with 95 percent confidence intervals of 0.99-1.11. There was no clear significant excess of any specific cancer type.During a postsurgery period of nearly two decades, results of our study did not support the hypothesis that either appendectomy or acute appendicitis are likely to be associated with malignant neoplasms.

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.

The incidence of brain and other intracranial tumors following head trauma was evaluated in a cohort of 228,055 Danish residents hospitalized because of concussion, fractured skull, or other head injury between 1977 and 1992 and followed for an average of eight years (maximum, 17 years). Traffic accidents, falls, and sports-related incidents were the usual causes of the injury. Malignant and benign neoplasms were identified by linking the study roster with records of the Danish Cancer Registry for the years 1977 to 1993. This approach precludes differential reporting of injuries by study participants as an explanation for any associations seen. Intracranial tumors of the nervous system occurred more often than expected based on incidence rates for the Danish population; however, most of the excess occurred during the first year after the injury and likely was due to the detection of tumors that were present before the injury occurred. Excluding the first year of follow-up, the standardized incidence ratio (SIR) was 1.15 (95 percent confidence interval [CI] = 0.99-1.32). The same general temporal pattern was seen for the major subtypes of brain tumor as for all types combined. SIRs after the first year were 1.0 for glioma (CI = 0.8-1.2), 1.2 for meningioma (CI = 0.8-1.7), and 0.8 for neurilemmoma (CI = 0.4-1.7). However, hemangioblastoma and hemangioma were more frequent than expected, based on 15 cases (SIR = 2.6, CI = 1.4-4.2). Results indicate that head trauma causes, at most, a small increase in the overall risk of brain tumors during the ensuing 15 years; however, a possible association with intracranial vascular tumors warrants further evaluation.

Although millions of women worldwide have received breast implants for cosmetic or medical reasons, possible late effects (in particular cancer) have not been well studied. To provide quantitative information on cancer occurrence among women undergoing breast implant surgery, 1,135 women treated for cosmetic reasons in Denmark were evaluated. Patients were identified using the nationwide Hospital Discharge Registry with linkage to the nationwide Danish Cancer Registry to determine subsequent cancer incidence. The average age of the women at implant surgery was 31 years, and the average follow-up was 8.4 years, up to a maximum of 17 years. Overall, 27 cancers developed after implant surgery compared with 24.7 expected based on incidence rates from the general population (standardized incidence ratio [SIR] = 1.1; 95% CI: 0.7-1.6). Eight breast cancers were observed vs. 7.8 expected (SIR = 1.0; 95% CI: 0.4-2.0). No evidence was found to link breast implants with increased cancer risk in the decade after surgery. While the results are encouraging, longer follow-up into later life will be necessary to assess fully any possible adverse effects.

Intuitively, breast tissue mass should be directly related to a woman's risk of breast cancer, simply because having more cells at risk would seem to increase the potential for malignant transformation. However, studies attempting to link breast size with breast cancer risk have been inconsistent. Limitations include crude measures of breast size, the inability to distinguish glandular from adipose tissue, and the confounding influence of co-factors such as obesity. A nationwide study in Denmark was undertaken to investigate the effect of breast reduction surgery on the subsequent risk of breast cancer, including an evaluation of the patterns of risk by age and time since surgery. The Danish Hospital Discharge Registry was used to identify women who underwent reduction mammaplasty between 1977 and 1992. Linkage based on personal identification numbers with the Danish Cancer Registry provided information on cancer incidence. Expected numbers of cancers were calculated from rates in the general population. Among 7,720 women whose breasts were surgically reduced, 182 cancers were subsequently observed cf 209 expected (standardized incidence ratio [SIR] = 0.9;95 percent confidence interval [CI] = 0.7-1.0). Breast cancer was significantly reduced by nearly 50 percent (29 observed cf 53.9 expected, SIR = 0.5, CI = 0.4-0.8), and accounted for the overall deficit in cancer. The risk reductions were related inversely to age at surgery, with significant deficits apparent only among women 40 years of age and older at surgery and especially among those over age 50 (SIR = 0.3). No clear trend was apparent with increasing years post-surgery. The findings indicate that breast reduction surgery among women over age 40 is associated with a lower subsequent risk of breast cancer, but the surgery and presumably glandular mass appear less closely related to breast cancer risk among younger women.

Only 2 small population-based studies have previously evaluated cancer risk in splenectomized patients. Our objective was thus to investigate cancer incidence following splenectomy for external trauma or for surgical treatment of non-malignant conditions of adjacent organs. Using the unique personal identification number assigned to each Swedish resident, we linked centralized hospitalization records with nationwide total population and cancer incidence data. We excluded cancers diagnosed within the first 12 months after splenectomy and computed standardized incidence ratios for 1,295 patients (contributing 14,390 person-years) splenectormized for external trauma and for 985 patients (contributing 8,91 1 person-years) whose splenectomy accompanied surgical treatment of non-malignant conditions of adjacent organs (mostly peptic ulcers), using age-, sex- and period-specific rates for cancer incidence derived from the entire Swedish population. Patients undergoing splenectomy for external trauma had no significant excess of total or site-specific cancers. Individuals splenectormized in conjunction with surgery for non-malignant conditions of adjacent organs had a non-significant 40% elevated risk of total cancer, with significant increases of lung and ovarian cancers. The excesses of lung and ovarian cancers may be due to chance, but we could not exclude the conditions for which the surgery was performed, other treatments or common predisposing factors (such as cigarette smoking, which has been linked with both peptic ulcer and lung cancer).