Nationwide study of cancer risk among hip replacement patients in Sweden.

BACKGROUND: Orthopedic implants and their fixatives contain materials with carcinogenic potential. Whether these implants are linked to subsequent cancer development remains unknown, mainly because large-scale, long-term follow-up data are scarce. METHODS: We conducted a nationwide cohort study in Sweden to examine cancer incidence among 116,727 patients who underwent hip replacement surgery during the period from 1965 through 1994. Through record linkage to the Swedish Cancer Register, we identified all incident cancers through 1995 in this population (693,954 person-years of observation). For each cancer type, the observed number of cases was divided by that expected in the general Swedish population to produce standardized incidence ratios (SIRs). RESULTS: Relative to the general population, the cohort had no overall cancer excess (SIR = 1.01; 95% confidence interval [CI] = 0.99 to 1.03). However, we observed elevated SIRs for prostate cancer (SIR = 1.16; 95% CI = 1.11 to 1.22) and melanoma (SIR = 1.15; 95% CI = 1.01 to 1.30) and a reduction in stomach cancer risk (SIR = 0.83; 95% CI = 0.75 to 0.92). Long-term follow-up (>or=15 years) revealed an excess of multiple myeloma (SIR = 1.86; 95% CI = 1.01 to 3.11) and a statistically nonsignificant increase in bladder cancer (SIR = 1.42; 95% CI = 0.98 to 1.99). There was no material increase in risk for bone or connective tissue cancer for either men or women in any follow-up period. CONCLUSIONS: In this, the largest study to date, hip implant patients had similar rates of most types of cancer to those in the general population. Although the excesses of melanoma, multiple myeloma, and prostate and bladder cancers may be due to chance, confounding, or detection bias and should be interpreted cautiously, they warrant further investigation because of the ever-increasing use of hip implants at younger ages.

Occupational risks for intracranial gliomas in Sweden.

With the use of the Cancer-Environment Registry, which links cancer incidence for the years 1961-79 with 1960 census information on occupation for all employed individuals in Sweden, a systematic population-based assessment according to employment classifications was made of the occurrence of intracranial gliomas. Statistically significant (P less than .05) increases in the incidence of intracranial gliomas were observed among several professional and white-collar occupations, possibly due in part to higher levels of diagnosis and reporting of this particular neoplasm. Significantly elevated rates were noted among male dentists, agricultural research workers, and public prosecutors and among female physicians and employees in the health care industry. For blue-collar workers, significant excesses were found among welders and metal cutters; glass, porcelain, or ceramic workers; cellulose plant employees; brick and tile workers; and women employed in the wool industry. Several findings of this survey may represent new clues to the etiology of intracranial gliomas, while other findings support observations reported in previous studies.

Racial differences in risk of oral and pharyngeal cancer: alcohol, tobacco, and other determinants.

BACKGROUND: In the United States, Blacks have increasingly higher rates of oral and pharyngeal cancer (oral cancer) than Whites, but determinants of the racial disparity have not been clear. PURPOSE: The purpose of this study was to explore reasons for the higher incidence of oral cancer among Blacks than Whites. METHODS: We used data from a large, population-based case-control study of oral cancer risk factors conducted in four areas of the United States. On the basis of interviews that ascertained characteristics of 1065 oral cancer patients (871 Whites and 194 Blacks) and 1182 controls (979 Whites and 203 Blacks), we examined racial differences in exposure prevalences and relative risks for a number of known etiologic factors, including tobacco and alcohol consumption, diet, and socioeconomic and other variables. To evaluate the extent to which the major risk factors explained the excess risk of oral cancer among Blacks, population-attributable risks were calculated. RESULTS: Differences with respect to alcohol consumption, especially among current smokers, emerged as the most important explanatory variables. After adjusting for smoking, heavy drinking (> or = 30 drinks/week) resulted in a 17-fold increased risk among Blacks and a ninefold increase among Whites. Among drinkers, Blacks tended to drink more than Whites. Also, a higher (P = .01) percentage of Blacks (37%) than Whites (28%) were current smokers, although there were little or no racial differences in relative risks or patterns of use for other smoking variables, including number of cigarettes smoked per day, years of smoking, and age started smoking. From population-attributable risk calculations, we estimated that differences in alcohol and tobacco use account for the bulk of the higher incidence of oral cancer among Blacks in the United States and that, in the absence of alcohol and tobacco, the rates of this cancer according to race (Black, White) and gender would be nearly equal. With regard to other potential etiologic factors, protective effects provided by higher dietary intake of fruits and vitamin C were more pronounced for Whites, while Blacks more often tended to be in sociodemographic and medical or dental health categories associated with increased risk. CONCLUSIONS: These analyses provide evidence that various environmental or lifestyle determinants of oral cancer may contribute to the higher oral cancer rates in Blacks than in Whites in the United States, but that patterns and risks associated with alcohol consumption, particularly among current smokers, are the most important contributors to the excess risk in Blacks. IMPLICATIONS: These findings suggest that the key to prevention of oral and pharyngeal cancers among both Blacks and Whites is reduced intake of alcoholic beverages and, because of strong interactive effects, the cessation of smoking.

Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer.

Interviews with 866 patients with cancer of the oral cavity and pharynx and 1249 controls of similar age and sex from the general population in four areas of the United States revealed increased risks associated with the regular use of mouthwash. Risks of oral cancer were elevated by 40% among male and 60% among female mouthwash users, after adjusting for tobacco and alcohol consumption. Risks among both sexes generally increased in proportion to duration and frequency of mouthwash use. The increased risks were confined to users of mouthwash high in alcohol content, consistent with the elevated risks associated with drinking alcoholic beverages. Except for a higher prevalence of leukoplakia among cases, little relationship was found with oral or dental conditions, although denture wearing was reported more often by patients with cancer of the gums. These findings, together with other studies, provide further incentive for clarifying the association between mouthwash use and oral cancer.

Occupational risks for bladder cancer among men in Sweden.

With the use of the Swedish Cancer-Environment Registry, census data on employment in 1960 were linked with registry data on bladder cancer during 1961-79. This hypothesis-generating study revealed for the first time associations between bladder cancer and employment in pulp and fiberboard manufacturing, in rope and twine making, and work as a dental technician. Statistically significant increases in risk were also found for several occupations previously associated with bladder cancer, including barbers and beauticians, artistic painters, toolmakers and machinists, and physicians, and employment in butcher shops, industrial chemical making, apparel manufacturing, and plumbing. Etiologic inferences cannot be made from this investigation, but the findings from this large national resource provide further clues to the occupational determinants of bladder cancer.

Connective tissue disease and other rheumatic conditions following cosmetic breast implantation in Denmark.

OBJECTIVE: To examine the occurrence of connective tissue diseases (CTDs) as well as ill-defined and other rheumatic conditions among Danish women with cosmetic silicone breast implants. PATIENTS AND METHODS: A total of 2761 women with breast implants and 8807 control subjects were identified from plastic surgery private clinics and from public hospital plastic surgery departments. Women operated on at plastic surgery private clinics were identified through the files of each clinic, while women operated on at public hospitals were identified using the nationwide Danish National Registry of Patients. The control group consisted of women who underwent cosmetic surgery other than breast implantation or who only had a consultation. All women were followed up from January 1, 1977, through December 31, 1996, through the Danish National Registry of Patients for the occurrence of CTD as well as ill-defined and other rheumatic conditions. For the study period January 1, 1977, through December 31, 1994, the Danish National Registry of Patients contains information on hospitalization only, whereas data on outpatient visits are included from 1995 on, thus improving the sensitivity of the data. The implant and control groups were compared with the Danish population rates for CTD and ill-defined and other rheumatic conditions, and a direct comparison between the implant and control groups was also performed. RESULTS: When compared with rates from the general population, no excess of definite CTD was observed in the implant cohorts. For ill-defined and other rheumatic conditions, statistically significant excesses of unspecified rheumatism were observed in both the implant and control cohorts when compared with national rates. A direct comparison between the implant and control cohorts found no material differences between the groups. CONCLUSIONS: The findings of this study support previous investigations and independent review panel conclusions that an association between silicone breast implants and definite CTDs is unlikely. The observation of an excess of unspecified rheumatism among women with implants and among control women suggests that women undergoing cosmetic plastic surgery have hospitalization rates for this condition in excess of those from the general population.

Neurologic disease among women with breast implants.

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.

Breast implants and risk of neurologic disease: a population-based cohort study in Sweden.

OBJECTIVE: To examine the risk of neurologic disorders among women with breast implants. BACKGROUND: Case reports in the literature have raised concern about a possible link between silicone breast implants and some types of neurologic disorders, but there is a dearth of epidemiologic studies in this area. METHODS: Through the nationwide Swedish hospital discharge register, we identified a population-based cohort of 7433 women with breast implants. A similarly identified cohort of 3351 women who underwent breast reduction surgery served as a comparison. The women were followed from 1972 (or date of breast surgery if it occurred later) through 1993 by means of record linkages and review of inpatient medical records. Ratios of observed to expected numbers, and relative risks (RR) with 95% confidence intervals (CI), were calculated as measures of the risk of neurologic diseases among women with implants. RESULTS: A direct comparison of the exposed (implant) versus comparison (breast reduction) groups, after exclusion of patients with pre-existing disease or incorrect neurologic diagnoses, showed no excess risk among implant patients (RR = 0.8; 95% CI = 0.5 to 1.4). When external rates derived from the background population were used as comparison, we found a small, statistically nonsignificant excess of neurologic disorders both in the breast implant (RR = 1.3; 95% CI = 0.9 to 1.9) and the breast reduction (RR = 1.5; 95% CI = 0.9 to 2.4) cohorts. CONCLUSION: Our results provide no support for the conjecture that breast implants cause neurologic disease.

Antipolymer antibodies in Danish fibromyalgia patients.

OBJECTIVE: To use a new immunologic assay to investigate antipolymer antibody (APA) levels in women with fibromyalgia (FM). METHODS: The study population consisted of 35 patients with FM and 129 controls. The controls were selected based on a prior history of breast surgery and the presence or absence of a prior hospital diagnosis of soft tissue rheumatism. Study subjects underwent blood sampling, including tests for antinuclear antibodies (ANA) and APA, a clinical examination, and an interview focusing on rheumatic complaints and self-reported disability. The severity of rheumatic symptoms/signs was scored from 1 (= none) to 5 (= severe) based on the clinical examination and the interview. RESULTS: FM patients in this study represented a broad spectrum of disease severity, with the majority having mild symptoms. FM patients had a higher symptom severity and myalgic scores than controls (p < 0.001 for both variables). Adjusting for symptom severity, a weak positive association between APA levels and FM was observed (p = 0.08). The APA level was inversely associated with age, i.e., decreasing APA levels were seen with increasing age (p = 0.008). CONCLUSION: FM patients tended to have slightly higher APA levels than controls when adjusted for symptom severity. APA levels declined with age, a finding that has not been reported previously. The APA test and its clinical relevance should be evaluated in future studies.

Rheumatic manifestations in danish women with silicone breast implants.

The aim of this study was to investigate whether women with silicone breast implants (SBI) present with a unique rheumatic symptomatology. We assessed the profile of rheumatic disease in six groups of women identified through Danish hospital and population registers, three groups of women with a prior hospital diagnosis of muscular rheumatism (a non-specific diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast sugery (n = 56). All women in the study population (n = 188) underwent a thorough clinical examination, blood tests and a personal interview. In all study groups soft-tissue rheumatism and degenerative diseases were the most frequent diagnoses. Women with a prior diagnosis of muscular rheumatism but no prior breast surgery had a significantly higher prevalence of soft-tissue rheumatism than those with breast implant or reduction surgery. No significant differences in the frequencies of rheumatic diseases were observed among the three groups of women without previous muscular rheumatism. No specific pattern of inflammatory rheumatic disorders or soft-tissue complaints was identified among the women with SBI, and blood tests for autoimmunity revealed no unique pattern. Overall, women with earlier rheumatism had significantly increased frequencies of rheumatic conditions than did those without. We found no evidence of a rheumatic symptomatology unique to women with silicone breast implants. Our study emphasises the need for consideration of prior rheumatic disease when evaluating rheumatic manifestations in women with SBI.

Prevalence of silicone breast implant rupture among Danish women.

The durability of silicone gel-filled breast implants is of concern, but there are few epidemiological studies on this issue. To date, most of the relevant findings are derived from studies of explantation, which suffer from bias by including women with symptoms or concerns about their implants. As part of a long-term magnetic resonance imaging study of the incidence of rupture, this study involved 271 women with 533 cosmetic breast implants who were randomly selected from among women who underwent cosmetic breast implantation from 1973 through 1997 at one public and three private plastic-surgery clinics in Denmark. The prevalence of rupture was determined from the first magnetic resonance screening. The images were evaluated by four independent readers, using a standardized, validated form. The outcomes under study were rupture, possible rupture, and intact implant. Ruptures were categorized as intracapsular or extracapsular. Overall, 26 percent of implants in 36 percent of the women examined were found to be ruptured, and an additional 6 percent were possibly ruptured. Of the ruptured implants, 22 percent were extracapsular. In multiple regression analyses, age of implant was significantly associated with rupture among second- and third-generation implants, with a 12-fold increased prevalence odds ratio for rupture of implants that were between 16 and 20 years of age, compared with implants between 3 and 5 years of age. Surgitek implants (Medical Engineering Corporation, Racine, Wis.) had a significantly increased prevalence odds ratio of 2.6 for rupture, compared with the reference implants. No significant association was found with the position (subglandular or submuscular) or the type of implant (single- or double-lumen). Extracapsular ruptures were significantly associated with a history of closed capsulotomy (p = 0.001). In the future, the authors plan to examine the women in their cohort with a second magnetic resonance imaging scan to establish the incidence of rupture, a parameter unknown to date in the literature, and to further characterize those factors associated with the actual risk of rupture.

Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden.

OBJECTIVE: To examine the relation between connective tissue disease and related conditions and breast implants. DESIGN: Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period. SETTING: Sweden. SUBJECTS: 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and 3353 women with breast reduction surgery. MAIN OUTCOME MEASURES: Subsequent hospitalisation for definite connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and Sjögren's syndrome) or related disorders. RESULTS: 29 women with implants were hospitalised for definite connective tissue disease compared with 25.5 expected based on general population rates (standardised hospitalisation ratio 1.1 (95% confidence interval 0.8 to 1.6)). There were no diagnoses of systemic sclerosis, and no significant excess in risk for polymyalgia rheumatica, fibromyalgia, and several related disorders. Among women who underwent breast reduction surgery, 14 were hospitalised for definite connective tissue disease compared with 10.5 expected (standardised hospitalisation ratio 1.3 (0.7 to 2.2)). Compared with the breast reduction group, women with breast implants showed a slight reduction for all definite connective tissue disease (relative risk 0.8 (95% confidence interval 0.5 to 1.4)). CONCLUSIONS: This large nationwide cohort study shows no evidence of association between breast implants and connective tissue disease.

Cancer risk among patients with finger and hand joint and temporo-mandibular joint prostheses in Denmark.

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.

Oral and pharyngeal cancers.

Trends for oral and pharyngeal cancers vary by anatomical subsite. For tumours of the tongue, mouth and pharynx (excluding nasopharynx), rates are rising in many areas of the world, particularly in Europe, at least in part attributable to rising alcohol consumption. Exceptions to this pattern occur in the USA, where incidence and mortality among whites are falling. There are mild downward trends in the incidence of lip, salivary gland and nasopharyngeal cancers, which (except for nasopharyngeal cancer among southern Chinese) occur at much lower frequency. The trends provide interesting clues to the causes of these cancers whose aetiology is partially but not fully understood.

Offspring health risk after cosmetic breast implantation in Sweden.

Case reports have suggested that children born to women with silicone breast implants may have an excess risk of rheumatic disease and/or esophageal disorders. In Sweden, the authors conducted a retrospective cohort study of 5,874 children born to women with cosmetic breast implants and 13,274 children born to women who had breast reduction surgery. Using national registers, they computed hospitalization rates for rheumatic and esophageal disorders, incidence rates for cancer, and prevalence rates for congenital malformations and perinatal death. Relative to children of women who had breast reduction surgery, children born to women who had cosmetic breast implants were not at excess risk of rheumatic disease (relative risk [RR] = 1.1; 95% confidence interval [95% CI], 0.2-5.3), esophageal disorders (RR = 1.0; 95% CI, 0.7-1.6), cancer (RR = 0.3; 95% CI, 0.0-2.5), congenital malformations in total (RR = 1.0; 95% CI, 0.6-1.5), or specifically involving the digestive organs (RR = 0.5; 95% CI, 0.2-1.3) or perinatal death (RR = 0.9; 95% CI, 0.5-1.8). The rates of these health outcomes among children born after a mother's implant surgery were also not significantly higher than among children born before a mother's implant surgery. This study provides no evidence that certain hypothesized health outcomes are more likely among the children of women with cosmetic breast implants.

Neurological disease among women with silicone breast implants in Denmark.

OBJECTIVES: To investigate the risk of neurological disease among women with cosmetic breast implants. MATERIAL AND METHODS: 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. 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.

Silicate antibodies in Danish women with silicone breast implants.

OBJECTIVES: To use a new immunological assay to evaluate silicate antibody levels in women with and without silicone breast implants (SBIs). METHODS: Women (n=186) were identified through Danish population-based registers and categorized into six groups defined by prior breast surgery (breast implantation/breast reduction/no breast surgery) and by the presence or absence of prior hospital diagnoses of soft-tissue rheumatism (muscular rheumatism, ICD-8 codes 717.90 and 717.99). The women underwent blood tests, a silicate antibody assay and a clinical examination. Severity of rheumatic symptoms/signs was scored from 1 (none) to 5 (severe). RESULTS: The level of silicate antibodies was not significantly different between the three groups with prior soft-tissue rheumatism (P > 0.5), with the lowest value among women with SBIs. Among women who had no prior diagnosis of soft-tissue rheumatism, silicate antibody levels were highest in women with SBIs (P < 0.01). No significant correlations were observed between silicate antibody levels and symptom severity scores. CONCLUSIONS: Silicate antibodies were not consistently associated with SBIs and were not correlated with rheumatic symptoms. The clinical relevance of these antibodies remains questionable.