A rebuttal: secret ties to industry and conflicting interests in cancer research.
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Conflict of Interest↗
Biomedical subjects
Joseph K McLaughlin
Publications and source records attributed to Joseph K McLaughlin.
Flavonoids and the risk of renal cell carcinoma.
Intake of flavonoids has been inversely related to the risk of various common neoplasms, but limited data exist on renal cell carcinoma (RCC). We used data from a case-control study conducted between 1994 and 2002 in four Italian areas to study the relation between major flavonoid classes and RCC. The study included 767 cases with incident, histologically confirmed RCC and 1,534 hospital controls admitted for acute, nonneoplastic conditions and matched with cases by study center, sex, and quinquennia of age. We applied published data on food and beverage content of six major classes of flavonoids to dietary information collected through a validated food frequency questionnaire. After adjustment for major recognized confounding factors and total energy intake, the odds ratios for subjects in the highest versus the lowest quintile of intake were 0.80 [95% confidence interval (95% CI), 0.58-1.11] for total flavonoids, 0.76 (95% CI, 0.56-1.03) for isoflavones, 0.94 (95% CI, 0.60-1.47) for anthocyanidins, 0.77 (95% CI, 0.56-1.06) for flavan-3-ols, 0.90 (95% CI, 0.67-1.21) for flavanones, 0.68 (95% CI, 0.50-0.93) for flavones, and 0.69 (95% CI, 0.50-0.95) for flavonols. Allowance for vegetable and fruit consumption only partly explained these inverse relations. Thus, flavonoids, and particularly flavones and flavonols, may account, at least in part, for the favorable role of plant foods on RCC.
Adult↗
Cellular telephone use and cancer risk: update of a nationwide Danish cohort.
BACKGROUND: The widespread use of cellular telephones has heightened concerns about possible adverse health effects. The objective of this study was to investigate cancer risk among Danish cellular telephone users who were followed for up to 21 years. METHODS: This study is an extended follow-up of a large nationwide cohort of 420,095 persons whose first cellular telephone subscription was between 1982 and 1995 and who were followed through 2002 for cancer incidence. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases in the cohort by the number expected in the Danish population. RESULTS: A total of 14,249 cancers were observed (SIR = 0.95; 95% confidence interval [CI] = 0.93 to 0.97) for men and women combined. Cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.97), acoustic neuromas (SIR = 0.73), salivary gland tumors (SIR = 0.77), eye tumors (SIR = 0.96), or leukemias (SIR = 1.00). Among long-term subscribers of 10 years or more, cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.66, 95% CI = 0.44 to 0.95), and there was no trend with time since first subscription. The risk for smoking-related cancers was decreased among men (SIR = 0.88, 95% CI = 0.86 to 0.91) but increased among women (SIR = 1.11, 95% CI = 1.02 to 1.21). Additional data on income and smoking prevalence, primarily among men, indicated that cellular telephone users who started subscriptions in the mid-1980s appeared to have a higher income and to smoke less than the general population. CONCLUSIONS: We found no evidence for an association between tumor risk and cellular telephone use among either short-term or long-term users. Moreover, the narrow confidence intervals provide evidence that any large association of risk of cancer and cellular telephone use can be excluded.
Cell Phone↗
Risk of hospitalization for angio-oedema among users of newer COX-2 selective inhibitors and other nonsteroidal anti-inflammatory drugs.
AIM: To examine the risk of angio-oedema among users of the newer cyclooxygenase (COX)-2 selective inhibitors celecoxib and rofecoxib and other non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in a population-based case-control study. METHODS: Cases of angio-oedema were identified from hospital discharge registries from three Danish counties between 1 January 2000 and 31 December 2003 (n = 377) and 10 matched population controls per case were selected from the Civil Registration System (n = 3747). Data on newer COX-2 selective inhibitor and other NSAID use (current and former) were obtained from prescription databases. Data on potential confounding factors were also collected. Conditional logistic regression was used to compute relative risks for angio-oedema according to drug exposure. RESULTS: The crude relative risks for the newer COX-2 selective inhibitors were higher than those for other NSAIDs. After adjustment for confounding, the relative risk for current use of newer COX-2 selective inhibitors was 0.96 [95% confidence interval (CI) 0.46, 2.03], whereas the risk for other NSAIDs was 1.77 (95% CI 1.23, 2.58). CONCLUSION: Our data support the hypothesis that newer COX-2 selective inhibitors are safe in relation to angio-oedema. However, given other current health concerns related to these drugs, their use should continue to be carefully monitored.
Adolescent↗
A cohort study of antihypertensive medication use and breast cancer among Danish women.
BACKGROUND: It has been suggested that specific antihypertensive medications (AHT) may either increase or decrease breast cancer risk. METHODS: We studied breast cancer incidence among 49,950 women in North Jutland, Denmark in order to determine if breast cancer risk is associated with specific classes of AHT use. Poisson regression analyses were used to calculate rate ratios for ever or exclusive use of each class of AHT, number of prescriptions for AHT, and years of follow-up. RESULTS: There was no statistically significant association between ever use of any AHT overall (RR = 0.95; 95% CI = 0.81-1.10) or any specific class of AHT (diuretics, beta blockers, calcium channel blockers (CCBs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin II antagonists) and breast cancer. CONCLUSIONS: This study should offer further reassurance to women currently using AHT that their medication use is unlikely related to breast cancer risk.
Adrenergic beta-Antagonists↗
Obesity and risk for chronic renal failure.
Few large-scale epidemiologic studies have quantified the possible link between obesity and chronic renal failure (CRF). This study analyzed anthropometric data from a nationwide, population-based, case-control study of incident, moderately severe CRF. Eligible as cases were all native Swedes who were aged 18 to 74 yr and had CRF and whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women) during the study period. A total of 926 case patients and 998 control subjects, randomly drawn from the study base, were enrolled. Face-to-face interviews, supplemented with self-administered questionnaires, provided information about anthropometric measures and other lifestyle factors. Logistic regression models with adjustments for several co-factors estimated the relative risk for CRF in relation to body mass index (BMI). Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three-fold excess risk for CRF, relative to BMI<25. Obesity (BMI>or=30) among men and morbid obesity (BMI>or=35) among women anytime during lifetime was linked to three- to four-fold increases in risk. The strongest association was with diabetic nephropathy, but two- to three-fold risk elevations were observed for all major subtypes of CRF. Analyses that were confined to strata without hypertension or diabetes revealed a three-fold increased risk among patients who were overweight at age 20, whereas the two-fold observed risk elevation among those who had a highest lifetime BMI of >35 was statistically nonsignificant. Obesity seems to be an important-and potentially preventable-risk factor for CRF. Although hypertension and type 2 diabetes are important mediators, additional pathways also may exist.
Adolescent↗
Long-term cancer risk among Swedish women with cosmetic breast implants: an update of a nationwide study.
Epidemiologic evidence does not support a consistently increased cancer risk among women with cosmetic breast implants, but few studies have assessed risk beyond 15 years. Swedish women who underwent cosmetic breast implantation for the first time between January 1, 1965, and December 31, 1993 (N = 3486), were followed through December 31, 2002. Cancer incidence was ascertained through the nationwide Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to compare cancer incidence of women with implants with women in the general population. Mean follow-up among women with breast implants was 18.4 years (range = 0.1-37.8 years). The incidence of breast cancer was below expectation (SIR = 0.7, 95% CI = 0.6 to 1.0), whereas lung cancer was above expectation (SIR = 2.2, 95% CI = 1.3 to 3.4). With respect to cancer overall and all other specific cancer sites, including brain cancer and sarcoma, non-Hodgkin lymphoma, and multiple myeloma, no statistically significantly increased or decreased SIRs were observed. Stratification by duration of follow-up revealed no statistically significantly increased or decreased SIR, with the exception of a two- to threefold excess of lung cancer among women followed for more than 15 years, which would be expected due to the high prevalence of smoking among the Swedish women with implants in our study.
Adult↗
Cancer risk among Danish women with cosmetic breast implants.
The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10-15 years after breast implantation. We extended follow-up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow-up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973-95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0-1.4), during a mean follow-up period of 14.4 years (range = 0-30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5-1.0), and an increased risk of non-melanoma skin cancer (SIR = 2.1; 95% CI = 1.5-2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non-melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8-1.2). With respect to other site-specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non-melanoma skin cancer of 1.1 (95% CI = 0.8-1.6), 0.7 (95% CI = 0.4-1.3) and 1.5 (95% CI = 0.8-2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non-melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants.
Adolescent↗
The epidemiology of renal cell carcinoma.
PURPOSE: We identified and examined risk factors for renal cell cancer, some of which may explain in part the trends of steadily increasing incidence rates, particularly in black Americans. MATERIALS AND METHODS: Epidemiological studies were identified through a MEDLINE(R) search of the literature through February 2006. A qualitative summary of the results of individual studies is presented. RESULTS: Cigarette smoking and obesity are the most consistently established causal risk factors, accounting for about 20% and 30% of renal cell cancers, respectively. Hypertension appears to independently influence renal cell cancer risk. Neither acetaminophen nor other analgesics have been convincingly linked with renal cell cancer. With respect to diet a general protective effect of fruit and vegetable consumption is the only consistently reported finding. For occupational factors the weight of the evidence provides no consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline or trichloroethylene exposure. Self-reported family history is associated with 2 to 3-fold increases in risk and the major inherited forms of renal cell cancer together account for about 2% of this malignancy. CONCLUSIONS: A further reduction in cigarette smoking, and a decrease in the rates of obesity and hypertension would likely moderate the increasing incidence of renal cell cancer. Epidemiological studies, including evaluation of gene-environment interactions, are needed to specifically identify reasons for the increasing incidence, particularly for assessing the roles of obesity and hypertension. Special attention should be focused on black Americans since their incidence rate recently increased to significantly surpass that in white Americans.
Adolescent↗
Epidemiologic aspects of renal cell carcinoma.
Renal cell cancer accounts for 2% of all new cancer cases worldwide. Incidence rates have been rising steadily around the world. In the United States, the rates have been rapidly increasing among black Americans, whose incidence rate has now surpassed that of white Americans. Cigarette smoking and obesity are the most consistently established causal risk factors, accounting for more than 20% and 30% of renal cell cancers, respectively. Hypertension, rather than antihypertensive drugs, appears to influence renal cell cancer development, although the mechanism is unknown. Analgesics have not been convincingly linked with renal cell cancer risk. In general, there appears to be a protective effect of fruit and vegetable consumption, although no particular component of diet has been clearly implicated. There are sporadic and inconsistent reports of occupations or occupational exposures being associated with this cancer. Epidemiologic studies are needed to identify reasons for the increasing incidence of renal cell cancer, with particular focus on why the incidence rate for black Americans has risen to significantly surpass that of white Americans.
Carcinoma, Renal Cell↗
Mortality among Rocketdyne workers who tested rocket engines, 1948-1999.
OBJECTIVE: The objective of this study was to evaluate potential health risks associated with testing rocket engines. METHODS: A retrospective cohort mortality study was conducted of 8372 Rocketdyne workers employed 1948 to 1999 at the Santa Susana Field Laboratory (SSFL). Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for all workers, including those employed at specific test areas where particular fuels, solvents, and chemicals were used. Dose-response trends were evaluated using Cox proportional hazards models. RESULTS: SMRs for all cancers were close to population expectations among SSFL workers overall (SMR = 0.89; CI = 0.82-0.96) and test stand mechanics in particular (n = 1651; SMR = 1.00; CI = 0.86-1.16), including those likely exposed to hydrazines (n = 315; SMR = 1.09; CI = 0.75-1.52) or trichloroethylene (TCE) (n = 1111; SMR = 1.00; CI = 0.83-1.19). Nonsignificant associations were seen between kidney cancer and TCE, lung cancer and hydrazines, and stomach cancer and years worked as a test stand mechanic. No trends over exposure categories were statistically significant. CONCLUSION: Work at the SSFL rocket engine test facility or as a test stand mechanic was not associated with a significant increase in cancer mortality overall or for any specific cancer.
Adult↗
Dietary factors and cancers of the renal pelvis and ureter.
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Body Mass Index↗
Use of nonaspirin NSAIDs and risk of lung cancer.
Epidemiologic evidence is conflicting regarding the potential for nonsteroidal antiinflammatory drugs (NSAIDs) to lower the risk of lung cancer. We thus determined the incidence of lung cancer among a cohort of over 242,000 adults in Denmark who had been issued NSAID prescriptions during 1991-2002 and calculated the relative risks of this cancer according to the numbers of prescriptions received. Similar analyses were conducted among a subset with chronic obstructive pulmonary disease, of whom the large majority was assumed to have been smokers, as an indirect control for smoking. Utilization of Danish registries ensured essentially complete and unbiased ascertainment of prescriptions and cancer outcomes. The relative risks of lung cancer among NSAID users redeeming 10 or more prescriptions vs. nonusers in the general population and among chronic obstructive pulmonary disease patients were 1.51 (95% CI = 1.33-1.71) and 1.55 (95% CI = 0.93-2.60) and tended to decline with decreasing numbers of NSAIDs prescribed. Separate analyses for adenocarcinoma and squamous cell carcinoma also failed to show reduced risks among NSAID users. Confounding by indication may have contributed to the increased risks, but the study provides no evidence to suggest that recent NSAID intake may be protective for lung cancer.
Aged↗
A nationwide epidemiologic study of breast cancer incidence following breast reduction surgery in a large cohort of Swedish women.
While it has been demonstrated that prophylactic mastectomy reduces breast cancer incidence among women at high risk, many women often consider this disfiguring surgery unacceptable. One alternative approach may be breast reduction surgery. In order to evaluate the long-term incidence of breast cancer following surgical removal of breast tissue, we have extended by 9 years the follow-up period of our earlier retrospective cohort study of Swedish women electing cosmetic breast reduction surgery (n=30,444) between 1965 and 1993, yielding an average of nearly 16 years of follow-up. Cancer incidence through 2002 was ascertained via the Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated comparing women who underwent breast reduction surgery with women in the general Swedish population. Breast cancer was observed in 443 women versus 624 expected for a statistically significant reduced SIR of 0.71 (95% CI=0.65-0.78). Analyses by age at surgery, time since surgery or calendar year of surgery revealed similar reductions in risk. Our study of over 30,000 women with long-term follow-up offers further evidence that women undergoing breast reduction surgery have reduced breast cancer risk. As the evidence from large-scale cohort studies accumulates, direct testing of this reduction in risk through clinical trials should be considered.
Adolescent↗
Re: "Mortality from Solid Cancers among Workers in Formaldehyde Industries".
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Cohort Studies↗
Use of plant stanol ester margarine among persons with and without cardiovascular disease: early phases of the adoption of a functional food in Finland.
BACKGROUND: The plant stanol ester margarine Benecol is a functional food that has been shown to lower effectively serum total and LDL-cholesterol. The purpose of this post-marketing study is to characterize users of plant stanol ester margarine with and without cardiovascular disease. METHODS: A cohort of plant stanol ester margarine users was established based on a compilation of 15 surveys conducted by the National Public Health Institute in Finland between 1996-2000. There were 29,772 subjects aged 35-84 years in the cohort. The users of plant stanol ester margarine were identified by the type of bread spread used. RESULTS: The plant stanol ester margarine was used as bread spread by 1332 (4.5%) subjects. Almost half (46%) of the users reported a history of cardiovascular disease. Persons with cardiovascular disease were more likely to use plant stanol ester margarine (8%) than persons without cardiovascular disease (3%). Users with and without cardiovascular disease seemed to share similar characteristics. In particular, they were elderly people with otherwise healthy life-styles and diet. They were less likely smokers, more likely physically active and less likely obese than nonusers. The users reported being in good or average health in general and having used cholesterol-lowering drugs. CONCLUSION: Plant stanol ester margarine seems to be used by persons for whom it was designed and in a way it was meant: as part of efforts for cardiovascular disease risk reduction.
Adult↗
Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study.
BACKGROUND: It remains uncertain if the excess cardiovascular risk of rofecoxib and celecoxib reported in clinical trials is present in routine practice and whether the use of other nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) also carries an increased cardiovascular risk. We performed a population-based case-control study to examine the risk of myocardial infarction (MI) among users of various categories of nonaspirin NSAIDs. METHODS: Using data from hospital discharge registries in the counties of North Jutland, Viborg, and Aarhus, Denmark, and the Danish Civil Registration System, we identified 10,280 cases of first-time hospitalization for MI and 102,797 sex- and age-matched non-MI population controls. All prescriptions for nonaspirin NSAIDs filled before the date of admission for MI were identified using population-based prescription databases. Relative risk estimates for MI were adjusted for a history of cardiovascular disease, hypertension, diabetes mellitus, chronic bronchitis or emphysema, alcoholism, liver cirrhosis, upper gastrointestinal bleeding, rheumatoid arthritis, systemic lupus erythematosus and the use of high-dose aspirin, platelet inhibitors, insulin or oral hypoglycemic drugs, antihypertensive drugs, lipid-lowering drugs, oral anticoagulants, nitrates, penicillamine, gold, oral glucocorticoids, and hormone therapy before the date of admission for MI. RESULTS: Current users of rofecoxib had an elevated risk estimate for hospitalization for MI compared with nonusers of any category of nonaspirin NSAIDs (adjusted relative risk [ARR], 1.80; 95% confidence interval [CI], 1.47-2.21). Increased risk estimates were also found among current users of celecoxib (ARR, 1.25; 95% CI, 0.97-1.62), other cyclooxygenase-2 selective inhibitors (ARR, 1.45; 95% CI, 1.09-1.93), naproxen (ARR, 1.50; 95% CI, 0.99-2.29), and other conventional nonaspirin NSAIDs (ARR, 1.68; 95% CI, 1.52-1.85). The highest ARRs were found among new users of all examined drug categories. CONCLUSIONS: Current and new users of all classes of nonaspirin NSAIDs had elevated relative risk estimates for MI. Although the increased risk estimates may partly reflect unmeasured bias, they indicate the need for further examination of the cardiovascular safety of all nonaspirin NSAIDs.
Adult↗
Cancer risk among statin users: a population-based cohort study.
Hydroxymethylglutaryl-CoA reductase inhibitors (statins) have been linked with potential chemopreventive effects; however, the data are conflicting. We conducted a population-based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry for the period 1989-2002. In a study population of 334,754 county residents, we compared overall and site-specific cancer incidence among 12,251 statin users (> or =2 prescriptions) with cancer incidence among nonusers and users of other lipid-lowering drugs (n = 1,257). Statistical analyses were based on age-standardization and Poisson regression analysis, adjusting for age, gender, calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular drugs. We identified 398 cancer cases among statin users during a mean follow-up period of 3.3 years (range 0-14 years). The age- and gender-standardized incidence rates of cancer overall were 596 per 100,000 person-years among statin users, 645 per 100,000 person-years among nonusers and 795 per 100,000 person-years among users of other lipid-lowering drugs. Adjusted rate ratios for cancer overall among statin users were 0.86 (95% CI, 0.78-0.95) compared to nonusers and 0.73 (95% CI, 0.55-0.98) compared to users of other lipid-lowering drugs. No significantly increased or decreased rate ratios were observed for any of the studied site-specific cancers (liver, colorectum, lung, breast, prostate, female genital organs and lymphatic and haematopoietic tissue), but most estimates tended to be less than 1.0. Stratification by duration of follow-up or number of prescriptions revealed no clear trends. In summary, individuals prescribed statins experienced a slightly reduced cancer incidence compared to population controls of nonusers and users of other lipid-lowering drugs. Larger and longer-term studies are needed to determine the potentially protective effect of statin use on cancer development.
Adult↗