Peter McCarron

The changing global patterns of female breast cancer incidence and mortality

One in ten of all new cancers diagnosed worldwide each year is a cancer of the female breast, and it is the most common cancer in women in both developing and developed areas. It is also the principal cause of death from cancer among women globally. We review the descriptive epidemiology of the disease, focusing on some of the key elements of the geographical and temporal variations in incidence and mortality in each world region. The observations are discussed in the context of the numerous aetiological factors, as well as the impact of screening and advances in treatment and disease management in high-resource settings.

Trends in Cervical Squamous Cell Carcinoma Incidence in 13 European Countries: Changing Risk and the Effects of Screening

Despite there being sufficient evidence for the effectiveness of screening by cytology in preventing cancer of the cervix uteri, screening policies vary widely among European countries, and incidence is increasing in younger women. This study analyzes trends in squamous cell carcinoma (SCC) of the cervix uteri in 13 European countries to evaluate effectiveness of screening against a background of changing risk. Age-period-cohort models were fitted and period and cohort effects were estimated; these were considered as primarily indicative of screening interventions and changing etiology, respectively. A unique set of estimates was derived by fixing age slopes to one of several plausible age curves under the assumption that the relation between age and cervical cancer incidence is biologically determined. There were period-specific declines in cervical SCC in several countries, with the largest decreases seen in northern Europe. A pattern emerged across Europe of escalating risk in successive generations born after 1930. In the western European countries, a decrease followed by a stabilization of risk by cohort was accompanied by period-specific declines. In southern Europe, stable period, but increasing cohort trends, were observed. Substantial changes have occurred in cervical SCC incidence in Europe and well-organized screening programs have been highly effective in reducing the incidence of cervical SCC. Screening and changing sexual mores largely explain the changing period- and cohort-specific patterns, respectively. The increasing risk in recent cohorts is of obvious concern particularly in countries where no screening programs are in place. Further investigation of the effectiveness of opportunistic screening is warranted as is the observation of differing risk patterns in young cohorts in countries with relatively similar societal structures.

A systematic review of population based epidemiological studies in Myasthenia Gravis

BackgroundThe aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed.MethodsStudies were identified using multiple sources and meta-analysis performed to calculate pooled estimates for IR, PR and MR.Results55 studies performed between 1950 and 2007 were included, representing 1.7 billion population-years. For All MG estimated pooled IR (eIR): 5.3 per million person-years (C.I.:4.4, 6.1), range: 1.7 to 21.3; estimated pooled PR: 77.7 per million persons (C.I.:64.0, 94.3), range 15 to 179; MR range 0.1 to 0.9 per millions person-years. AChR MG eIR: 7.3 (C.I.:5.5, 7.8), range: 4.3 to 18.0; MuSK MG IR range: 0.1 to 0.32. However marked variation persisted between populations studied with similar methodology and in similar areas.ConclusionsWe report marked variation in observed frequencies of MG. We show evidence of increasing frequency of MG with year of study and improved study quality. This probably reflects improved case ascertainment. But other factors must also influence disease onset resulting in the observed variation in IR across geographically and genetically similar populations.

Mortality in Barrett’s oesophagus: results from a population based study

Background: Patients with Barrett’s oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett’s oesophagus register. Methods: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. Results: Overall mortality was not raised in Barrett’s patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84–107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317–1231)) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37–93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111–311)). Mortality rates from all other causes were similar to those of the general population. Conclusions: This study demonstrates that the overall mortality rate in patients with Barrett’s oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.

Exposures in childhood, adolescence and early adulthood and breast cancer risk: a systematic review of the literature.

A growing body of work indicates that exposures over the life course have important roles to play in the aetiology of breast cancer. This review synthesises the literature that has been published in the area of early life events and female breast cancer risk. The review finds some evidence, primarily from cohort studies on the relationship between birthweight and breast cancer, to suggest that in utero events are related to breast cancer risk in adulthood. Strong evidence to support a positive association between height and breast cancer exists. Postulated mechanisms for this relationship include the role of early diet in subsequent disease risk, and the influence of endogenous growth factors mediating the relationship. There is some evidence to suggest that leg length is the component of height which is generating the observed associations between height and breast cancer. There is no consistent pattern of association between relative weight in childhood or adolescence and risk of breast cancer. The evidence to suggest an association between physical activity in early life and breast cancer risk is convincing from case-control studies, but is not fully substantiated by the results of three cohort studies. There are inconsistent results regarding the association between smoking at a young age and breast cancer risk. There is little evidence for an association between passive smoking in early life and breast cancer risk. No clear association between early drinking and breast cancer risk exists. These results are discussed in relation to possible underlying mechanisms and health promotion strategies which could reduce breast cancer risk.

The genetics of coronary heart disease: The contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Body mass index in early and mid-adulthood, and subsequent mortality: a historical cohort study

BACKGROUND: The aim of this study was to investigate the associations between body mass index (BMI) in early and mid-adulthood, and BMI change between these ages, and mortality.METHODS: Historical cohort study of 629 men, who had height and weight measured at the Student Health Service of the University of Glasgow in 1948–1949 (median age 22 y) and who reported their weight in a postal questionnaire in 1963–1966 (median age 38 y). The participants were followed up until April 2002 (mean follow-up: 35 y). During this time, 124 men died, 68 of cardiovascular disease (CVD) and 33 of cancer.FINDINGS: Mean BMI increased from 21.4 kg/m2 (standard deviation (s.d.): 2.2 kg/m2) in early adulthood to 24.2 kg/m2 (s.d.: 3.0 kg/m2) in mid-adulthood. All-cause mortality was associated with being overweight (BMI≥25 kg/m2) at age 22 but not at age 38, adjusted hazard ratio (HR): 1.85 (95% confidence interval (CI) 1.09–3.13) and 1.05 (95% CI: 0.73–1.52), respectively. BMI at age 22 y was more strongly associated with CVD mortality than was BMI at age 38 y, adjusted HR22 y: 2.41 (95% CI: 1.26–4.60) and HR38 y: 1.33 (95% CI: 0.82–2.16). There was no clear relationship between cancer mortality and BMI at either age: HR22 y: 0.68 (95% CI: 0.16–2.91), HR38 y: 0.90 (95% CI: 0.44–1.84), although relatively few men died of cancer in the follow-up period. Similar patterns were seen for obesity (BMI≥30 kg/m2) as for being overweight. Analyses of weight patterns indicated particularly detrimental effects of overweight persisting from early to mid-adulthood.CONCLUSIONS: BMI in early adulthood is positively related to CVD mortality in later life in men. The risk associated with early adulthood adiposity appeared to be greater than that in mid-adulthood. We did not demonstrate an association between weight gain and later mortality. These results reinforce the need to stem the obesity epidemic in children and young adults.

Secular changes in blood pressure in childhood, adolescence and young adulthood: systematic review of trends from 1948 to 1998.

One plausible reason for the decline in cardiovascular disease (CVD), and in particular stroke, in the last century is population reductions in blood pressure. Blood pressure tracks from childhood into adulthood, and early-life blood pressure is associated with increased cardiovascular risk but few studies have reported on blood pressure trends among young individuals who are free of CVD and not taking antihypertensive medication. Knowledge of such trends may improve understanding of the causes of hypertension and enhance prevention. We report that declines in blood pressure have been taking place in high-income countries in 5 to 34-year-olds of both sexes and from a range of ethnic groups for at least the last 50 years, indicating that exposures acting in early life are important determinants of blood pressure. Possible explanations for these favourable trends include improvements in early-life diet and there is also intriguing evidence suggesting that blood pressure may be programmed by sodium intake in infancy. Occurring throughout the blood pressure distribution, these trends may have made important contributions to declining CVD rates. There may therefore be scope for intervening in early life to prevent high blood pressure in adulthood, and the downward trends reported in several recent studies suggest that the prevalence of adult hypertension and cardiovascular risk will continue to decline. However, persisting high rates of CVD in the developed world, the impending CVD epidemic in developing countries, along with increasing childhood obesity, and the possibility that favourable blood pressure trends may be plateauing point to the need for enhanced measures to control blood pressure, and for further research to improve understanding of its determinants.

Social circumstances in childhood and cardiovascular disease mortality: prospective observational study of Glasgow University students

Adverse socioeconomic circumstances in childhood have been related to increased cardiovascular disease (CVD) risk in adulthood in most, but not all, studies.1 The findings of such studies can be difficult to interpret given the association of childhood social circumstances with social conditions and behavioural risk factors for CVD in adulthood. Statistical adjustment for these, however, generally indicates an important additional contribution of childhood socioeconomic background.2 In this study we investigate the association between childhood circumstances and CVD mortality among male former students of Glasgow University, who will have experienced a relatively homogeneous and privileged adulthood social environment. Students attending the University of Glasgow between 1948–68 were invited to participate in a medical examination carried out by the student health department.3 Data collected included sociodemographic data, details of health behaviours and measured blood pressure. Participants were traced through the National Health Service Central Register. Full details are reported elsewhere.3The social class of the fathers of …

Life course breast cancer risk factors and adult breast density (United Kingdom)

Objective To determine whether risk factors in childhood and early adulthood affect later mammographic breast density. Methods: Subjects were 628 women who attended a medical examination at the University of Glasgow Student Health Service (1948–1968), responded to a questionnaire (2001) and had a screening mammogram in Scotland (1989–2002). Mammograms (median age of 59years) were classified using a six category classification (SCC) of breast density percent. Logistic regression was used to determine associations between risk factors and having a high-risk mammogram (≥25 dense). Results: In multi-variable analyses, high-risk mammograms were associated with parity (adjusted odds ratio (OR) per child: 0.77 (95 confidence interval (CI) 0.61–0.99)), age at first birth, OR per year: 1.05 (0.99–1.11), smoking at university, OR smokers versus non-smokers: 0.58 (0.36–0.92) and body mass index (BMI) while at university, OR per 1kg/m20.75 (0.69–0.82). No associations with SCC were found for age at menarche, birth weight, oral contraceptive (OC) use, height, leg length or exercise at age 20. Conclusions: We confirm previous findings that breast density is affected by reproductive events and some anthropometric measures, however most of the risk factors acting throughout the life course which we examined were not closely related to adult breast density.