Limited use of local anesthesia for open inguinal hernia repair: a qualitative study.

PURPOSE: Local anesthesia for open inguinal hernia repair is recommended by guidelines but is rarely used in clinical practice in several countries. This study aimed to explore physician's considerations in choosing type of anesthesia and barriers for implementing local anesthesia for open hernia repair in clinical practice. METHODS: We performed individual semi-structured interviews of surgeons and anesthesiologists. Transcribed data were condensed, coded, categorized, and formulated into themes in an inductive qualitative content analysis. RESULTS: Twenty two participants from seven public hospitals were included in the study. Participants described a standardized setup for general anesthesia with use of intravenous propofol/remifentanil and a laryngeal mask and were generally satisfied with this setup. Their considerations in choosing anesthesia could be described in four themes: (1) Intraoperative pain and quality of surgical technique, (2) Communication and teaching, (3) Logistics, and (4) Clinical routines. CONCLUSION: Participants considered intraoperative pain and quality of surgical technique, communication and teaching, logistics, and clinical routines as important factors when choosing anesthesia for open inguinal hernia repair and these factors acted as barriers for implementing of local anesthesia in Danish public hospitals. In this setting, implementation strategies should, therefore, be multimodal to address these barriers. The potential workload in such an effort should be justified by evidence supporting specific types of local anesthesia comapared with general anesthesia with use of propofol/remifentanil and a laryngeal mask.

Mortality and Urological Complications After Open Groin Hernia Repair in Local, General, and Regional Anesthesia: A Nationwide Linked Register Study.

BACKGROUND AND AIMS: The choice of anesthesia method may influence mortality and postoperative urological complications after open groin hernia repair. We aimed to investigate the association between type of anesthesia and incidence of urinary retention, urethral stricture, prostate surgery, and 1-year mortality after open groin hernia repair. MATERIALS AND METHODS: Data were linked from the Danish Hernia Database, the national patient register, and the register of causes of death. We investigated data on male adult patients receiving open groin hernia repair from 1999 to 2013 with either local anesthesia, regional anesthesia, or general anesthesia. In relation to the type of anesthesia, we compared mortality and urological complications up to 1 year postoperatively. We adjusted for covariates in a logistic regression assessing urological complications and with the Cox regression assessing mortality. RESULTS: We included 113,069 open groin hernia repairs in local anesthesia, regional anesthesia, or general anesthesia. The risk of urinary retention adjusted for covariates was higher after both general anesthesia (adjusted odds ratio = 1.64, 95% confidence interval = 1.05-2.57, p = 0.031) and regional anesthesia (odds ratio = 2.99, 95% confidence interval = 1.67-5.34, p < 0.0005) compared with local anesthesia. The adjusted risk of prostate surgery was also higher for both general anesthesia (odds ratio = 1.58, 95% confidence interval = 1.23-2.03, p < 0.0005) and regional anesthesia (odds ratio = 1.90, 95% confidence interval = 1.40-2.58, p < 0.0005) compared with local anesthesia. Type of anesthesia did not influence 1-year mortality or the risk for urethral stricture. CONCLUSION: Patients undergoing open groin hernia repair in local anesthesia experience the lowest rate of urological complications and have equally low mortality compared with patients undergoing repair in general anesthesia or regional anesthesia.

Network meta-analysis of urinary retention and mortality after Lichtenstein repair of inguinal hernia under local, regional or general anaesthesia.

BACKGROUND: Urinary retention and mortality after open repair of inguinal hernia may depend on the type of anaesthesia. The aim of this study was to investigate possible differences in urinary retention and mortality in adults after Lichtenstein repair under different types of anaesthesia. METHODS: Systematic searches were conducted in the Cochrane, PubMed and Embase databases, with the last search on 1 August 2018. Eligible studies included adult patients having elective unilateral inguinal hernia repair by the Lichtenstein technique under local, regional or general anaesthesia. Outcomes were urinary retention and mortality, which were compared between the three types of anaesthesia using meta-analyses and a network meta-analysis. RESULTS: In total, 53 studies covering 11 683 patients were included. Crude rates of urinary retention were 0·1 (95 per cent c.i. 0 to 0·2) per cent for local anaesthesia, 8·6 (6·6 to 10·5) per cent for regional anaesthesia and 1·4 (0·6 to 2·2) per cent for general anaesthesia. No death related to the type of anaesthesia was reported. The network meta-analysis showed a higher risk of urinary retention after both regional (odds ratio (OR) 15·73, 95 per cent c.i. 5·85 to 42·32; P < 0·001) and general (OR 4·07, 1·07 to 15·48; P = 0·040) anaesthesia compared with local anaesthesia, and a higher risk after regional compared with general anaesthesia (OR 3·87, 1·10 to 13·60; P = 0·035). Meta-analyses showed a higher risk of urinary retention after regional compared with local anaesthesia (P < 0·001), but no difference between general and local anaesthesia (P = 0·08). CONCLUSION: Local or general anaesthesia had significantly lower risks of urinary retention than regional anaesthesia. Differences in mortality could not be assessed as there were no deaths after elective Lichtenstein repair. Registration number: CRD42018087115 ( https://www.crd.york.ac.uk/prospero).

ANTECEDENTES: La retención de orina y la mortalidad tras la reparación abierta de las hernias inguinales puede depender del tipo de anestesia. El objetivo de este estudio fue investigar posibles diferencias en la retención de orina y mortalidad en adultos tras reparación de Lichtenstein bajo diferentes métodos anestésicos. MÉTODOS: Se efectuaron búsquedas sistemáticas en las bases de datos Cochrane, PubMed y Embase con la última revisión el 1 de agosto de 2018. Los estudios elegibles incluyeron pacientes adultos sometidos a reparación electiva de hernia inguinal unilateral mediante la técnica de Lichtenstein bajo anestesia local, regional o general. Las variables de resultados fueron la retención de orina y la mortalidad, comparándose los tres tipos de anestesia con metaanálisis y un metaanálisis en red. RESULTADOS: En total se incluyeron 53 estudios con un total de 11.683 pacientes. Las tasas crudas de retención de orina fueron del 0,1% (i.c. del 95% 0,0-0,2%) para la anestesia local, del 8,6% (i.c. del 95% 6,6-10,5%) para la anestesia regional y del 1,4% (i.c. del 95% 0,6-2,2%) para la anestesia general. No se observó mortalidad relacionada con el tipo de anestesia. El metaanálisis en red mostró un riesgo más elevado de retención de orina tras la anestesia regional (razón de oportunidades, odds ratio, OR 15,73 (i.c. del 95% 5,85-42,32), P < 0,001) y anestesia general (OR 4,07 (i.c. del 95% 1,07-15,48), P = 0,040) en comparación con la anestesia local y un riesgo más alto tras la regional en comparación con la anestesia general (OR 3,87 (i.c. del 95% 1,10-13,60), P = 0,035). Los metaanálisis mostraron un riesgo más alto de retención de orina tras la anestesia regional en comparación con la anestesia local (P < 0,001), pero sin diferencias entre anestesia general y local (P = 0,08). CONCLUSIÓN: La anestesia local o general presentaba un riesgo significativo menor de retención urinaria en comparación con la anestesia regional. Las diferencias en mortalidad no pudieron ser evaluadas ya ningún paciente falleció tras la reparación electiva de Lichtenstein.

Familial risk of non-Hodgkin lymphoma by sex, relationship, age at diagnosis and histology: a joint study from five Nordic countries.

We aimed to estimate stratified absolute (cumulative) and relative (standardized incidence ratios; SIRs) risks of non-Hodgkin lymphoma (NHL) in relatives of NHL patients. A cohort of 169 830 first-degree relatives of 45 406 NHL patients who were diagnosed between 1955 and 2010 in five European countries was followed for cancer incidence. The lifetime (0-79 year) cumulative risk of NHL in siblings of a patient with NHL was 1.6%, which represents a 1.6-fold increased risk (SIR=1.6, 95% confidence interval (CI)=1.2-1.9) over the general population risk. NHL risk among parent-offspring pairs was increased up to 1.4-fold (95% CI=1.3-1.5; lifetime risk 1.4%). The lifetime risk was higher when NHL was diagnosed in a sister (2.5% in her brothers and 1.9% in her sisters) or a father (1.7% in his son). When there were ⩾2 NHL patients diagnosed in a family, the lifetime NHL risk for relatives was 2.1%. Depending on sex and age at diagnosis, twins had a 3.1-12.9% lifetime risk of NHL. Family history of most of the histological subtypes of NHL increased the risk of concordant and some discordant subtypes. Familial risk did not significantly change by age at diagnosis of NHL in relatives. Familial risk of NHL was not limited to early onset cases.

Statin use and risk for ovarian cancer: a Danish nationwide case-control study.

BACKGROUND: Limited data suggest that statin use reduces the risk for ovarian cancer. METHODS: Using Danish nationwide registries, we identified 4103 cases of epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk-set sampled controls. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial ovarian cancer overall, and for histological types, associated with statin use. RESULTS: We observed a neutral association between ever use of statins and epithelial ovarian cancer risk (OR=0.98, 95% CI=0.87-1.10), and no apparent risk variation according to duration, intensity or type of statin use. Decreased ORs associated with statin use were seen for mucinous ovarian cancer (ever statin use: OR=0.63, 95% CI=0.39-1.00). CONCLUSIONS: Statin use was not associated with overall risk for epithelial ovarian cancer. The inverse association between statin use and mucinous tumours merits further investigation.

Low-dose aspirin use and the risk of ovarian cancer in Denmark.

BACKGROUND: A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low-dose aspirin and the risk of ovarian cancer. PATIENTS AND METHODS: We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. RESULTS: For 4103 ovarian cancer cases and 58 706 population controls, the adjusted OR for epithelial ovarian cancer associated with ever use (≥2 prescriptions) of low-dose aspirin was 0.94 (95% CI 0.85-1.05). ORs for epithelial ovarian cancer were lower with the use of 150 mg aspirin tablets (OR = 0.82; 95% CI 0.68-0.99) and with long-term use (≥5 years) of low-dose aspirin (OR = 0.77; 95% CI 0.55-1.08). Continuous long-term use of low-dose aspirin, defined as close consecutive prescriptions, was associated with a further reduction in OR (0.56; 95% CI 0.32-0.97). For histological types of epithelial ovarian cancer, the strongest inverse associations with low-dose aspirin use were seen for mucinous and endometrioid tumours. CONCLUSION: This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer.

Familial risks in nervous system tumours: joint Nordic study.

BACKGROUND: Familial nervous system cancers are rare and limited data on familial aspects are available particularly on site-specific tumours. METHODS: Data from five Nordic countries were used to analyse familial risks of nervous system tumours. Standardised incidence ratios (SIRs) were calculated for offspring of affected relatives compared with offspring of non-affected relatives. RESULTS: The total number of patients with nervous system tumour was 63 307, of whom 32 347 belonged to the offspring generation. Of 851 familial patients (2.6%) in the offspring generation, 42 (4.7%) belonged to the families of a parent and at least two siblings affected. The SIR of brain tumours was 1.7 in offspring of affected parents; it was 2.0 in siblings and 9.4 in families with a parent and sibling affected. For spinal tumours, the SIRs were much higher for offspring of early onset tumours, 14.0 for offspring of affected parents and 22.7 for siblings. The SIRs for peripheral nerve tumours were 16.3 in offspring of affected parents, 27.7 in siblings and 943.9 in multiplex families. CONCLUSION: The results of this population-based study on medically diagnosed tumours show site-, proband- and age-specific risks for familial tumours, with implications for clinical genetic counselling and identification of the underlying genes.

Autoimmune disease and risk for Parkinson disease: a population-based case-control study.

OBJECTIVE: Inflammatory mediators are increased in autoimmune diseases and may activate microglia and might cause an inflammatory state and degeneration of dopaminergic neurons in the brain. Thus, we evaluated whether having an autoimmune disease increases the risk for developing Parkinson disease (PD). METHODS: A population based case-control study was conducted in Denmark of 13,695 patients with a primary diagnosis of PD recorded in the Danish National Hospital Register during the period 1986-2006. Each case was matched on year of birth and sex to 5 population controls selected at random from among inhabitants of Denmark who were alive at the date of the patient's diagnosis. The main exposure measure was a hospital diagnosis of 1 of 32 selected autoimmune diseases recorded 5 or more years before the index date in the files of the Danish Hospital Register. RESULTS: We observed no overall association between a diagnosis of autoimmune disease and risk for subsequent PD (odds ratio 0.96, 95% confidence interval 0.85-1.08). In a subgroup of patients with autoimmune diseases with systemic involvement, primarily rheumatoid arthritis, we saw a decrease in risk for PD of 30%. CONCLUSIONS: Our results do not support the hypothesis that autoimmune diseases increase the risk for Parkinson disease. The decreased risk observed among patients with rheumatoid arthritis might be explained by underdiagnosis of movement disorders such as Parkinson disease in this patient group or by a protective effect of the treatment with anti-inflammatory drugs over prolonged periods.

Proton pump inhibitors and risk of gastric cancer: a population-based cohort study.

Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new users of PPI (n=18,790) or histamine-2-antagonists (H2RAs) (n=17,478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8-2.0) among PPI users and 1.2 (95% CI: 0.8-1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or non-users. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.

Radiotherapy for childhood cancer and risk for congenital malformations in offspring: a population-based cohort study.

Offspring of childhood cancer survivors may be at risk of genetic disease due to the mutagenic cancer treatments received by their parents. Congenital malformations were evaluated in a population-based cohort study of 1715 offspring of 3963 childhood cancer survivors and 6009 offspring of 5657 survivors' siblings. The Danish Central Population Register, Cancer Registry and Hospital Register were used to identify study subjects and congenital malformations. Gonadal and uterine radiation doses were characterized based on standard radiation-treatment regimens. The prevalence of congenital malformations at birth in offspring of survivors (44 cases, 2.6%) was slightly higher but not statistically different from that of offspring of siblings (140 cases, 2.3%) [prevalence proportion ratio (PPR), 1.1; 95% confidence interval, 0.8-1.5] or of the general population (observed-to-expected ratio, 1.2; 0.9-1.6). Including malformations diagnosed later in life did not change the ratios appreciably. The risk for malformations was slightly higher in the offspring of irradiated parents than in that of non-irradiated parents (PPR 1.2 vs 1.0) but was unrelated to gonadal dose. This study provides evidence that cancer therapy of children does not increase the risk for malformations in their offspring. Continued monitoring of genetic risks among their offspring, however, is warranted.

Risk of second malignant neoplasms after childhood central nervous system malignant tumours: an international study.

PURPOSE: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. METHODS: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study.

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985--1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6-5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8-8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.

Use of NSAIDs, smoking and lung cancer risk.

We investigated the risk of lung cancer in relation to non-steroidal anti-inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls for whom we had information on use of NSAIDs, from a prescription database covering all pharmacies in Denmark since 1995, and self-reported NSAID use, smoking habits and other potential confounders. Associations were expressed as odds ratios, assessed by logistic regression in unmatched analyses. After controlling for smoking habits, length of education and concomitant use of acetaminophen, we found a slightly decreased relative risk of 0.86 (95% confidence intervals, 0.65-1.14) for lung cancer associated with any use of NSAIDs. The risk decreased significantly (P=0.02) with increasing numbers of dispensed prescriptions per year during the 1-3 years before the index date with a relative risk of 0.49 (0.28-0.84) among those with four or more prescriptions per year during this period. Our findings suggest that regular use of NSAIDs is associated with a slightly or moderately reduced risk for lung cancer.

G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring.

In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G(2) chromosomal radiosensitivity assay was undertaken on a group of 23 Danish survivors of childhood and adolescent cancer, a control group comprising their partners and a group of 38 of their offspring. In addition, the previously reported in-house control group from Westlakes Research Institute (WRI) was extended to 27 individuals. When using the 90th percentile cutoff for the WRI control group, the proportion of individuals with elevated radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively, with significant differences between the WRI control group and the cancer survivor group (P=0.002) and the offspring group (P<0.001). However, while the comparisons with the WRI control group support an association of chromosomal radiosensitivity with cancer predisposition, when the partner control group was used to define the radiosensitivity cutoff point, no significant differences in radiosensitivity profiles were found between the partner control group and either the cancer survivor group or the offspring group. The failure to distinguish between the G(2) aberration profiles of the apparently normal group of partners and the cancer survivor group suggests that any association with cancer should be viewed with caution, but also raises questions as to the suitability of the partners of cancer survivors to act as an appropriate control group. Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

The risk of a second cancer after hospitalisation for venous thromboembolism.

Although venous thromboembolism (VTE) is common in patients with cancer, it is not known if it is associated with risk of a second malignancy. Using the Danish Cancer Registry and National Registry of Patients, we studied a population-based cohort of 6285 patients with cancer who had an episode of VTE. The risk of a second cancer was compared with that among 30 713 cancer patients without VTE, matched for age, sex, cancer site and year of diagnosis. Overall, the relative risk for a second cancer diagnosis was 1.3 (95% confidence interval (CI) 1.1-1.4). However, the excess risk varied with the time from the initial cancer diagnosis to the thrombotic event. If the thrombotic episode occurred within the first year, the relative risk for a second cancer was 1.0 (95% CI 0.9-1.3), but if the VTE occurred more than 1 year after the initial cancer, the overall relative risk for a second cancer was 1.4 (95% CI 1.2-1.7), with strong associations for cancers of the digestive organs, ovary and prostate. The association between VTE and subsequent incident cancer extends to patients who already have had a cancer diagnosis.

Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia.

Epidemiological studies have consistently shown elevated rates of breast cancer among female blood relatives of patients with ataxia telangiectasia (AT), a rare autosomal recessive disease. A large proportion of the members of AT families are carriers of AT-causing gene mutations in ATM (Ataxia Telangiectasia Mutated), and it has been hypothesised that these otherwise healthy carriers are predisposed to breast cancer. This is an extended and enlarged follow-up study of cancer incidence in blood relatives of 75 patients with verified AT in 66 Nordic families. Blood relatives were identified through population registry linkages, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. The ATM mutation carrier probabilities of relatives were assigned from the combined information on location in family, consanguinity, if any, and supplementary carrier screening in some families. Among the 1445 blood relatives of AT patients, 225 cancers were observed, with 170.4 expected, yielding a standardised incidence ratio (SIR) of 1.3 (95% confidence interval (CI), 1.1-1.4). Invasive breast cancer occurred in 34 female relatives (SIR, 1.7; 95% CI, 1.2-2.4) and was diagnosed in 21 women before the age of 55 years (SIR, 2.9; 95% CI, 1.8-4.5), including seven mothers of probands (SIR, 8.1; 95% CI, 3.3-17). When the group of mothers was excluded, no clear relationship was observed between the allocated mutation carrier probability of each family member and the extent of breast cancer risk. We concluded that the increased risk for female breast cancer seen in 66 Nordic AT families appeared to be restricted to women under the age of 55 years and was due mainly to a very high risk in the group of mothers. The findings of breast cancer risk in mothers, but not other likely mutation carriers, in this and other studies raises questions about the hypothesis of a simple causal relationship with ATM heterozygosity.

CLL family 'Pedigree 14' revisited: 1947-2004.

The notion that inherited predisposition contributes to the development of haematological malignancies is generally thought of as being a relatively new idea. However, Videbaek made a clear enunciation of such a hypothesis in 1947, from a study of tumour incidence in relatives of patients with different leukaemias. To gain further insight into inherited susceptibility to chronic lymphocytic leukaemia (CLL), we followed up the descendants of Videbaek's 'Pedigree 14' series of families. Using the Danish medical and pedigree databases, complete tracing of 222 descendants of the original 57 family members was achieved. To date, 10 family members have been diagnosed with CLL, one with T-cell lymphoma and 17 with nonhaematological cancers, including five with breast cancer. The detailed follow up of this family provides further support for inherited predisposition to CLL and illustrates the value of follow-up studies of previously published family material for genetic analyses.

The intrauterine origin of male breast cancer: a birth order study in Denmark.

First pregnancies are known to have higher oestrogen levels than later ones and first-born women are at increased breast cancer risk compared with later-born women. We hypothesized that a birth order effect might be even more evident in male breast cancer patients, in whom oestrogens in adult life are generally low. In a population-based study in Denmark involving 77 male breast cancer patients and 288 population controls, first-born men compared with later-born men had a relative risk of 1.71 for the disease (95% confidence interval (CI) 1.00-2.92). This result is in line with that seen in female breast cancer cases and indicates that male breast cancer may have roots in the intrauterine life, oestrogens being a likely mediator.

Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study.

Numerous studies and meta-analyses have shown that hormone replacement therapy (HRT) for menopausal symptoms increases the risk of developing breast cancer, estimated to be 2.3% for each year of use. The influence of different oestrogen-progestin regimens has still not been fully evaluated. Using longitudinal data from the population-based prescription database of the county of North Jutland, Denmark, and the Danish Cancer Registry, we examined the risk of developing breast cancer in relation to HRT in a cohort of 78,380 women aged 40-67 years from 1989 to 2002. A total of 1462 cases of breast cancer were identified during a mean follow-up of 10 years. Use of HRT did not increase the risk of breast cancer in women aged 40-49 years. Restricting the cohort to 48,812 women aged 50 years or more at entry, of whom 15 631 were HRT users, we found an increased risk associated with current use of HRT (relative risk 1.61, 95% confidence interval 1.38-1.88). The risk increased with increasing duration of use and decreased with time since last HRT prescription, reaching unity after 5 years. No material risk difference was observed among the various HRT-regimens. This population-based cohort study provides further confirmation that HRT increases the risk of developing breast cancer in women aged 50 years or more.