Søren Friis

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 (≥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.

Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study

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.

Atypical cancer pattern in patients with Parkinson's disease

Among 14 088 patients, with a primary diagnosis of Parkinsons 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 Parkinsons 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.

L-type calcium channel blockers and Parkinson disease in Denmark

This study was undertaken to investigate L‐type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood–brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk.

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population‐based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943–2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24–1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non‐melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.

Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries.

The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population‐based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person‐years of follow‐up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person‐years and the age‐, sex‐ and calendar period‐specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83–1.90) and the 20‐year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20‐year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking.

Confounding by indication in epidemiologic studies of commonly used analgesics

Confounding by indication is a bias frequently encountered in observational epidemiologic studies of drug effects. Because the allocation of treatment in observational studies is not randomized and the indication for treatment may be related to the risk of future health outcomes, the resulting imbalance in the underlying risk profile between treated and comparison groups can generate biased results. Confounding by indication is often present in studies of drugs that are not widely prescribed, because the indications for their use are narrow and not likely to be present in comparison groups; however, this bias is also observed in the study of widely used over-the-counter and prescription drugs, as exemplified by studies of analgesics. In this article we review examples from the published literature to demonstrate how confounding by indication can affect the findings of pharmacoepidemiologic studies relating analgesic use to various health outcomes.

A population-based cohort study of the risk of colorectal and other cancers among users of low-dose aspirin

Using data from the population-based Prescription Database of North Jutland County and the Danish Cancer Registry, we compared cancer incidence among 29 470 individuals prescribed low-dose aspirin at maximum doses of 150 mg with expected incidence based on county-specific cancer rates, during a 9-year study period. We observed 2381 cancer cases compared with 2187 expected, yielding a standardised incidence ratio (SIR) of 1.09 (95% confidence interval (CI), 1.05–1.13). No apparent risk reductions were found for cancers of the colon (SIR, 0.9; 95% CI, 0.7–1.1) or rectum (SIR, 1.0; 95% CI, 0.8–1.2), or for other site-specific cancers. Increased SIRs were observed for kidney cancer (SIR, 1.4; 95% CI, 1.1–1.7) and brain cancer (SIR, 1.7; 95% CI, 1.3–2.2), although the excess in the latter was confined to the first year of follow-up. Stratification by number of prescriptions and duration of follow-up revealed no apparent trends. The SIR for colorectal cancer was close to unity (SIR, 0.9; 95% CI, 0.6–1.2) among persons with 10 or more prescriptions who were followed for at least 5 years. Our results do not support a major protective effect of low-dose aspirin on the development of colorectal or other cancers. The observed excesses of kidney and brain cancers are not likely to be causally related to the use of low-dose aspirin.

Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark.

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.

Surgical intervention and capsular contracture after breast augmentation: a prospective study of risk factors.

Epidemiologic data on local complications after breast augmentation are scarce. In particular, few prospectively collected data are available on modern breast implants on this issue. Using data from the Danish Registry for Plastic Surgery of the Breast, the authors examined determinants of surgery-requiring complications and capsular contracture grades III to IV among 2277 women who underwent cosmetic breast implantation from June 1999 through April 2003. During an average follow-up period of 1.6 years after implantation, 4.3% of these women (3% of implants) required secondary surgery as a result of short-term complications. The most frequent clinical indications for surgery were displacement of the implant (38%), capsular contracture grades III to IV (16%), ptosis (13%), and hematoma (11%). Overall, the authors found that inframammary incision and subglandular placement were associated with decreased risks of developing complications requiring surgical intervention, whereas implants larger than 350 mL increased the risk of such complications (relative risk [RR], 2.3; 95% confidence interval [CI], 1.3–4.0). Thirty-nine Baker III to IV capsular contractures were identified, of which 22 were treated surgically within the study period. Submuscular placement of the implant decreased the risk of capsular contracture grades III to IV (RR, 0.3; 95% CI, 0.2–0.8), whereas surgical routes other than inframammary and drainage of implant cavity were associated with increased risk of capsular contracture. Current surgical practices and modern implants used for breast augmentation produce fewer short-term complications than procedures and devices of the past. This prospective study indicates that surgical procedures are more important predictors for local (short-term) complications than implant or patient characteristics.