Search

Purpose Evidence of differences in the etiology of, and poorer survival from, proximal colon compared to the distal colorectum, necessitates research into its risk factors. This systematic review summarizes the evidence on medication use and proximal colon cancer risk. Methods MEDLINE and EMBASE were searched for prospective studies investigating nine medication groups, namely non-steroidal anti-inflammatory drugs (NSAIDs), exogenous hormones, i.e., hormone replacement therapy (HRT) or oral contraceptives (OCs), statins, proton pump inhibitors, anti-hypertensives, metformin (an antidiabetic), antidiarrheals or laxatives, and the risk of proximal colon cancer. Narrative synthesis and meta-analyses, using random effects models to estimate risk ratios (RRs) and 95% confidence intervals (CIs), were conducted. Results Twenty nine publications investigating NSAIDs (n = 13), exogenous hormones [HRT (n = 9) or OCs (n = 4)] statins (n = 5), anti-hypertensives (n = 1), and metformin (n = 1) were included. Summary RRs reported a protective effect of aspirin use (RR 0.80, 95% CI 0.73–0.89) but no associations between HRT (RR 0.92, 95% CI 0.83–1.02), OC (RR 1.06, 95% CI 0.98–1.14) or statin use (RR 0.94, 95% CI 0.67–1.31), and proximal colon cancer incidence compared to never/non-use. One study on metformin and one on anti-hypertensives reported no association. Sources of between-study heterogeneity included study design, period of exposure ascertainment, exposure source, and exposure comparison, but this exploration was hindered by the small numbers of studies. Conclusion Despite some studies on NSAID or HRT use, evidence on the impact of a range of medications on proximal colon cancer risk is limited. This highlights the need for more research to inform chemoprevention strategies.

Supplementary Material Supplementary appendix Download Summary This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about £2 per month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre-existing occlusive vascular disease (secondary prevention) and in 500 patients (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. The only serious adverse events that have been shown to be caused by long-term statin therapy—ie, adverse effects of the statin—are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50–100 patients (ie, 0·5–1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.

Background: Mammographic density (MD) has been found to be an independent risk factor for breast cancer. Although data from twin studies suggest that MD has a strong genetic component, the exact genes involved remain to be identified. Alterations in stromal composition and the number of epithelial cells are the most predominant histopathological determinants of mammographic density. Interactions between the breast stroma and epithelium are critically important in the maturation and development of the mammary gland and the cross-talk between these cells are mediated by paracrine growth factors and cytokines. The potential impact of genetic variation in growth factors and cytokines on MD is largely unknown. Methods: We investigated the association between 89 single nucleotide polymorphisms (SNPs) in 7 cytokine/growth-factor genes (FGFR2, IGFBP1, IGFBP3, TGFB1, TNF, VEGF, IL6) and percent MD in 301 premenopausal women (aged 50 to 55 years) participating in the Norwegian Breast Cancer Screening Program. We evaluated the suggestive associations in 216 premenopausal Singapore Chinese Women of the same age. Results: We found statistically significant associations between 9 tagging SNPs in the IL6 gene and MD in Norwegian women; the effect ranged from 3–5% in MD per variant allele (p-values=0.02 to 0.0002). One SNP in the IL6 (rs10242595) significantly influenced MD in Singapore Chinese women. Conclusion: Genetic variations in IL6 may be associated with MD and therefore may be an indicator of breast cancer risk in premenopausal women.