Cancer risk in persons receiving prescriptions for paracetamol: A Danish cohort study

Friis, Søren; Nielsen, Gunnar Lauge; Mellemkjær, Lene; McLaughlin, Joseph K.; Thulstrup, Ane Marie; Blot, William J.; Lipworth, Loren; Vilstrup, Hendrik; Olsen, Jørgen H.

doi:10.1002/ijc.1581

Cited by 47 publications

(81 citation statements)

References 27 publications

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“…Harris et al (1999) reported an OR of 0.84 among paracetamol users in a cohort of 32 505 women. Additionally, paracetamol has been previously linked to a decreased risk of ovarian cancer, another hormone-related cancer (Cramer et al, 1998;Rodriguez et al, 1998;Friis et al, 2002). In our study, we observed that users of paracetamol presented a reduced risk of breast cancer.…”

Section: Discussionsupporting

confidence: 61%

Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

Rodrı́guez

González‐Pérez

2004

Br J Cancer

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We conducted a cohort study with a nested case -control analysis to evaluate the effect of anti-inflammatory drugs in breast cancer incidence using the General Practice Research Database. Women taking aspirin and paracetamol for 1 year or longer had an odds ratio (OR) of 0.77 (95 percent confidence interval (95% CI): 0.62,0.95) and 0.76 (95% CI: 0.65,0.88), respectively, compared to nonusers. Daily doses of aspirin (75 mg) and paracetamol (up to 2000 mg) showed the greatest reduced risk. Use of non-aspirin nonsteroidal anti-inflammatory drugs for more than 1 year was not associated with a reduced risk of breast cancer (OR ¼ 1.00 (95% CI: 0.84, 1.17), and the corresponding estimate among users with at least 2 years duration was similar. Our findings suggest that aspirin at cardioprophylactic doses as well as paracetamol at analgesic doses is associated with a reduced risk of breast cancer. There is mounting epidemiological evidence suggesting that nonsteroidal anti-inflammatory drugs (NSAIDs) may substantially reduce the risk of colorectal cancer (Thun et al, 1991;García Rodríguez and Huerta-Á lvarez, 2000). The effects of NSAIDs in other cancers have also been extensively studied in the last decade. Nonsteroidal anti-inflammatory drugs have been shown to prevent breast cancer in animal models (Lala et al, 1997;Robertson et al, 1998). Proposed mechanisms commonly involve the inhibition of cyclooxygenase-2 (COX-2) (Sjodahl, 2001), the enzyme responsible for the production of various prostaglandins that play a key role in the proliferation of tumour tissue; there is accumulating evidence that NSAIDs may have the ability to restore apoptosis and inhibit angiogenesis (Thun et al, 2002).Observational studies of the effect of NSAIDs in breast cancer have shown inconclusive results through a meta-analysis, including data from 15 studies that concluded that NSAIDs could be associated with a small decrease in risk (Khuder and Mutgi, 2001). However, the association between breast cancer incidence and glucocorticoid therapy has been hardly explored. Results from in vitro studies suggest that glucocorticoids have a direct inhibitory effect on proliferation of mammary cancer cells (Goya et al, 1993). However, to our knowledge, this hypothesis has not been tested in an epidemiological study.We conducted a cohort study with a nested caseÀcontrol analysis to evaluate the effect of anti-inflammatory drugs in breast cancer incidence using the General Practice Research Database (GPRD). MATERIALS AND METHODSWe used data from the GPRD. This database contains computerised information entered by general practitioners (GPs) in the UK (García Rodríguez and Pérez Gutthann, 1998). Data on over two million patients are systematically recorded and sent anonymously to the Medicines and Healthcare products Regulatory Agency (MHRA), which collects and organises this information in order to be used for research projects. The computerised information includes demographics, details from general practitioner's visits, diagnoses from specialist's re...

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Section: Discussionsupporting

confidence: 61%

Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

Rodrı́guez

González‐Pérez

2004

Br J Cancer

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“…39,40 The clinical data on this association, however, are limited and conflicting. 4,13,35,41 When interpreting these discrepancies, our lack of information on over-the-counter acetaminophen should be taken into account. Given the high skin cancer incidence and the widespread and frequent use of NSAIDs, a preventive effect of these agents may have important public health implications.…”

Section: Discussionmentioning

confidence: 99%

Nonsteroidal anti‐inflammatory drugs and the risk of skin cancer

Johannesdottir

Chang

Mehnert

et al. 2012

Cancer

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BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, which are involved in carcinogenesis. Therefore, the authors of this report examined the association between NSAID use and the risk of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: From 1991 through 2009, all incident cases of SCC (n ¼ 1974), BCC (n ¼ 13,316), and MM (n ¼ 3242) in northern Denmark were identified. Approximately 10 population controls (n ¼ 178,655) were matched to each case by age, gender, and county of residence. The use of aspirin, other nonselective NSAIDs, or selective COX-2 inhibitors was ascertained through a prescription database. Conditional logistic regression analyses adjusted for potential confounders were used to compute odds ratios as estimates of incidence rate ratios (IRRs). RESULTS: For NSAIDs overall, ever use (>2 prescriptions) compared with nonuse ( 2 prescriptions) was associated with a decreased risk of SCC (IRR, 0.85; 95% confidence interval [CI], 0.76-0.94) and MM (IRR, 0.87; 95% CI, 0.80-0.95), especially for long-term use (!7 years) and high-intensity use (>25% prescription coverage during the total duration of use). NSAID use was not associated with a reduced risk of BCC overall (IRR, 0.97; 95% CI, 0.93-1.01), but the risk of BCC at sites other than the head and neck was reduced in association with long-term use (IRR, 0.85; 95% CI,) and high-intensity use (IRR, 0.79; 95% CI, 0.69-0.91). All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors (diclofenac, etodolac, and meloxicam). CONCLUSIONS: The current results indicated that NSAID use may decrease the risk of SCC and MM.

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“…In observational studies, the association between commonly used anti-inflammatory drugs and ovarian cancer remains unclear. A Danish cohort study found no evidence of a protective effect of paracetamol [53], and a case-control study conducted in the USA concluded that, although non-significant, the observed risk estimates appeared to be compatible with a small decrease of risk by regular (more than three times a week for a period of at least 6 months) aspirin use [54].…”

Section: Use Of Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 95%

Risk factors and risk reduction of breast and ovarian cancer

Brekelmans

2003

Current Opinion in Obstetrics and Gynecology

114

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Purpose of review Breast and ovarian cancer remain a significant burden for women living in the Western world. This paper reviews the risk factors and current strategies to prevent these diseases. Recent findingsEstablished factors associated with the risk of breast cancer include family history, reproductive factors and lactation, as well as age at menarche and menopause. Hormone replacement therapy increases the risk, whereas oral contraceptives probably confer no increased risk. Alcohol moderately increases the risk, whereas a diet rich in folate and carotenoids might be protective. The role of other dietary factors, smoking and physical exercise remain unclear. Important risk factors for ovarian cancer are reproductive factors and possibly the longterm use of hormone replacement therapy. The risk is decreased by oral contraceptives. In carriers of a BRCA1 or BRCA2 gene mutation, prophylactic surgery can significantly reduce the risk of breast as well as ovarian cancer. Tamoxifen may be considered as a chemopreventive agent in women with a high risk of breast cancer, including carriers of a BRCA2 mutation, but is probably not effective in BRCA1 carriers. Summary During the period of this review, the importance of several known risk factors was confirmed, whereas the effects of other factors became more clear. Chemoprevention and prophylactic surgery have emerged as preventative options that can reduce the risk of breast and ovarian cancer.

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Cancer risk in persons receiving prescriptions for paracetamol: A Danish cohort study

Cited by 47 publications

References 27 publications

Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

Nonsteroidal anti‐inflammatory drugs and the risk of skin cancer

Risk factors and risk reduction of breast and ovarian cancer

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