L J Murray

Dietary glycaemic index, glycaemic load and endometrial and ovarian cancer risk: a systematic review and meta-analysis.

Long-term consumption of a high glycaemic index (GI) or glycaemic load (GL) diet may lead to chronic hyperinsulinaemia, which is a potential risk factor for cancer. To date, many studies have examined the association between GI, GL and cancer risk, although results have been inconsistent, therefore our objective was to conduct a systematic review of the literature. Medline and Embase were systematically searched using terms for GI, GL and cancer to identify studies published before December 2007. Random effects meta-analyses were performed for endometrial cancer, combining maximally adjusted results that compared risk for those in the highest versus the lowest category of intake. Separate analysis examined risk by body mass index categories. Five studies examining GI and/or GL intake and endometrial cancer risk were identified. Pooled effect estimates for endometrial cancer showed an increased risk for high GL consumers (RR 1.20; 95% CI: 1.06–1.37), further elevated in obese women (RR 1.54; 95% CI: 1.18–2.03). No significant associations were observed for GI. Only two studies examined ovarian cancer and therefore no meta-analysis was performed, but results indicate positive associations for GL also. A high GL, but not a high GI, diet is positively associated with the risk of endometrial cancer, particularly among obese women.

Vitamin D status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart's Project.

SummaryIn girls, a plateau in parathyroid hormone (PTH) was observed at a 25-hydroxyvitamin D (25(OH)D) concentration of approximately 60xa0nmol/l. In boys, there was no plateau in PTH concentrations as 25(OH)D concentration increased. A 25(OH)D threshold of 60xa0nmol/l appears to have implications for bone health outcomes in both girls and boys.IntroductionOur objective was to investigate if there is a threshold 25(OH)D concentration where a plateau in PTH concentration is evident and to examine the impact of this relationship on bone mineral density (BMD) and bone turnover in a representative sample of adolescents.MethodsWe conducted a cross-sectional analysis among 1,015 Northern Irish adolescents aged 12 and 15xa0years. Serum 25(OH)D, PTH, osteocalcin, type 1 collagen cross-linked C-telopeptide (CTx), and BMD of the nondominant forearm and heel were measured. Nonlinear regression analysis was used to model the association between 25(OH)D and PTH.ResultsIn girls, a plateau in PTH was observed at a 25(OH)D concentration of approximately 60xa0nmol/l (PTHu2009=u200947.146u2009+u2009370.314u2009×u2009exp(−0.092u2009×u200925(OH)D)) while no plateau in PTH was observed in boys (PTHu2009=u200942.144u2009+u200956.366u2009×u2009exp(−0.022u2009×u200925(OH)D)). Subjects with 25(OH)D levels <60xa0nmol/l had significantly higher osteocalcin concentrations (Pu2009<u20090.05) compared with those who had ≥60xa0nmol/l, while no significant (Pu2009>u20090.05) differences were noted for CTx concentrations. In girls only, nondominant forearm BMD but not heel BMD was significantly higher (Pu2009=u20090.046) in those with 25(OH)D concentrationsu2009≥u200960xa0nmol/l.ConclusionsSerum 25(OH)D levels above 60xa0nmol/l in Northern Irish adolescent girls prevent an increase in serum PTH levels and maintaining 25(OH)D >60xa0nmol/l in both girls and boys may lead to improved bone health outcomes.

A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer

Background:Epidemiological studies have suggested a protective effect of cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drugs in breast cancer risk and disease progression. We performed a systematic review to evaluate the frequency of COX-2 expression in normal breast epithelium, ductal carcinoma in situ of breast (DCIS), DCIS-adjoining invasive breast cancer, microinvasive carcinoma of the breast (MICB) and invasive breast cancer.Methods:Literature searches were carried out on MEDLINE, EMBASE and Web of Science from their commencement until September 2010. Primary studies examining COX-2 expression by immunohistochemistry methodology were included. Meta-analyses were carried out using random effects models for individual study estimates of COX-2 expression and pooled to give an overall estimate.Results:The pooled prevalences (95% confidence intervals) of COX-2 expressions were 53% (44–61) in DCIS studies and 42% (36–49) in the invasive breast cancer studies. There were too few studies involving normal breast epithelium, DCIS-adjoining invasive breast cancer and MICB to conduct meta-analyses.Conclusion:The findings from our meta-analyses have shown similar COX-2 expression in DCIS and invasive breast cancer. This may suggest the involvement of COX-2 in early carcinogenesis. Further studies of COX-2 expression in DCIS are required to investigate the use of COX-2 as a potential drug target for prevention of disease progression in DCIS.

Statins and pancreatic cancer risk: a nested case-control study.

ObjectiveTo investigate the relationship between statin use and pancreatic cancer risk.MethodsA nested case–control study was conducted within the UK GPRD. Cases had a diagnosis of primary malignant neoplasia of the exocrine pancreas. Controls were matched with cases on general practice site, sex and year of birth. Exposure of interest was exposure to statins since entry into the GPRD until 1xa0year before the case diagnosis date. Conditional logistic regression analyses were used to generate ORs and 95% CI associated with statin use compared to non-use.ResultsA total of 1,141 pancreatic cancer cases and 7,954 controls were identified. Any use of a statin since entry into the GPRD (excluding the year prior to diagnosis) was not associated with the risk of pancreatic cancer OR 0.93 (95% CI, 0.76–1.14). Neither dose nor duration of statin use affected pancreatic cancer risk. When dose and duration of statin use combined were assessed, no evidence of reduced risk was seen for long-term users of high-dose statins OR 0.71 (0.42–1.20). Statin type (simvastatin vs atorvastatin) was not associated with pancreatic cancer risk.ConclusionStatin use at doses for managing hypercholesterolaemia, in a UK population, was not associated with the risk of exocrine pancreatic cancer.

Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case–control study

Background:The relationship between use of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) and pancreatic cancer risk has yet to be examined. Data from a range of studies suggest biologically plausible mechanisms, whereby these drugs (or the conditions for which they are prescribed) may affect pancreatic cancer risk. The objective of this study was to investigate the relationship between use of PPIs/H2RAs and pancreatic cancer risk.Methods:A nested case–control study was conducted within the UK general practice research database (GPRD). Cases had a diagnosis of exocrine pancreatic cancer and controls were matched to cases on general practice site, sex and year of birth. Exposure to PPIs and to H2RAs since entry into GPRD until 2 years before the diagnosis date (corresponding date in controls) and in the 5 years before the diagnosis date were separately assessed. Conditional logistic regression analyses were used to generate odds ratios (ORs) and 95% confidence intervals (CIs) associated with PPI or H2RA use compared with nonuse.Results:Ever use of PPIs since entry into the GPRD (excluding the 2 years prior to diagnosis) was not associated with risk of pancreatic cancer; OR (95% CI) 1.02 (0.85–1.22). Neither the dose nor the duration of PPI or H2RA use was associated with pancreatic cancer risk. No consistent patterns of association were seen when cumulative exposure (dose and duration) to these drugs was examined separately or together.Conclusion:PPI/H2RA use, in a UK population, was not associated with pancreatic cancer risk.

Non-steroidal anti-inflammatory drug and aspirin use and the risk of head and neck cancer

Background:Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect.Methods:Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC.Results:Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use.Conclusion:Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.

Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project

Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations.Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents.Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN.Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype.Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

AbstractPurposenPre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.MethodsnUsing prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95xa0% confidence intervals (CIs) for cancer-specific mortality.ResultsOverall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7xa0%. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95xa0% CI 0.84–1.26), lung (adjusted HR 1.06, 95xa0% CI 0.96–1.16), breast (adjusted HR 0.81, 95xa0% CI 0.62–1.07), or colorectal (adjusted HR 0.88, 95xa0% CI 0.77–1.01) cancer patients. Dose–response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.ConclusionsThere was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Non-steroidal anti-inflammatory drug use and cervical cancer risk: A case-control study using the Clinical Practice Research Datalink

PURPOSEnNon-steroidal anti-inflammatory drugs (NSAIDs) have many anticarcinogenic properties via the inhibition of cyclooxygenase 2 (COX-2). Only one study, a cohort study examining risk of all cancers, investigated their role in cervical cancer with inconsistent findings between non-aspirin NSAIDs and aspirin. The aim of this study was to further investigate NSAID/aspirin use and cervical cancer risk.nnnMETHODSnUsing the United Kingdom Clinical Practice Research Datalink, 724 women diagnosed with cervical cancer between 1 January, 1995 and December 2010 were compared to 3479 women (without cervical cancer) matched on year of birth and general practice. Conditional logistic regression analysis adjusted for smoking, sexually transmitted infections, HRT and contraceptive use, was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for cervical cancer risk among users of any oral NSAIDs, non-aspirin NSAIDs and aspirin, as assessed from primary care prescribing data.nnnRESULTSnExcluding the year prior to diagnosis, there was no association in adjusted analyses between ever vs. never use of an NSAID (OR 0.92, 95% CI 0.77-1.09), non-aspirin NSAID (OR 0.95, 95% CI 0.80-1.13) or low-dose aspirin (OR 1.07, 0.80-1.44) and cervical cancer risk. In analysis of daily defined doses, there was no association with cervical cancer risk comparing the highest users to non-users of NSAIDs (OR 0.98, 95% CI 0.69-1.39) or non-aspirin NSAIDs (OR 1.00, 95% CI 0.70-1.43) or low-dose aspirin (OR 1.04, 95% CI 0.59-1.81).nnnCONCLUSIONnThis large historical cohort study found no evidence of an association between non-aspirin NSAID or aspirin use and cervical cancer risk.

Nutritional Status of Breast Cancer Survivors 1 Year after Diagnosis: A Preliminary Analysis from the Malaysian Breast Cancer Survivorship Cohort Study

BACKGROUNDnLifestyle factors, such as diet, body weight, and physical activity, are linked to better survival after breast cancer (BC) diagnosis. A high percentage of the Malaysian population is overweight or obese. In addition, studies have shown a disparity in survival among Malaysian women compared with other higher-income countries. The Malaysian Breast Cancer Survivorship Cohort (MyBCC) study aims to study lifestyle factors that affect survival in BC survivors. These are the preliminary findings on the nutritional status of Malaysian BC survivors.nnnOBJECTIVEnOur aim was to evaluate the nutritional status of BC survivors at 1 year after diagnosis.nnnDESIGNnThis was a cross-sectional study of 194 participants from the MyBCC study, recruited within 1 year of their diagnosis. Participants completed a 3-day food diary.nnnPARTICIPANTSnMalaysian women (aged 18 years and older) who were newly diagnosed with primary BC, managed at the University Malaya Medical Center, and able to converse either in Malay, English, or Mandarin were included.nnnMAIN OUTCOME MEASURESnDietary intake and prevalence of overweight or obesity among participants 1 year after diagnosis were measured.nnnSTATISTICAL ANALYSES PERFORMEDnStudents t test and analysis of variance or its equivalent nonparametric test were used for association in continuous variables.nnnRESULTSnAbout 66% (n=129) of participants were overweight or obese and >45% (n=86) had high body fat percentage 1 year after diagnosis. The participants diets were low in fiber (median=8.7 g/day; interquartile range=7.2 g/day) and calcium (median=458 mg/day; interquartile range=252 mg/day). Ethnicity and educational attainment contributed to the differences in dietary intake among participants. Higher saturated fat and lower fiber intake were observed among Malay participants compared with other ethnic groups.nnnCONCLUSIONSnOverweight and obesity were highly prevalent among BC survivors and suboptimal dietary intake was observed. Provision of an individualized medical nutrition therapy by a qualified dietitian is crucial as part of comprehensive BC survivorship care.