M Okasha

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.

Blood pressure in young adulthood and mortality from cardiovascular disease

Blood pressure measured in young adult men is positively associated in later life with increased cardiovascular disease mortality. The implication of this finding is that risk of cardiovascular disease starts in early life.

Age at menarche: secular trends and association with adult anthropometric measures

BACKGROUND Age at menarche has been used as a marker of environmental conditions during childhood. Previous work has shown trends of decreasing age at menarche throughout the 19th century, but reported trends in the 20th century have been less consistent. The nature of the relationship between age at menarche and adult life anthropometric measures may be important in understanding the importance of this measure on disease in later life. AIM To establish whether mean age at menarche changed during the first half of the 20th century, and to determine the nature of associations between age at menarche and anthropometric measures in young adulthood. SUBJECTS AND METHODS 3433 female students, who were born between 1919 and 1952 and who attended health checks at the student health service of the University of Glasgow between 1948 and 1968. RESULTS Mean age at menarche decreased from 13.2 years in the earliest born to 12.5 years in the latest born students. These results were not explained by changes in socio-demographic factors. Menarcheal age was positively associated with height and negatively associated with weight and BMI, results independent of socio-demographic and behavioural factors. CONCLUSIONS The falling age at menarche described here may be related to nutritional influences in the first half of the 20th century. The influence of menarche on BMI in early adulthood may have important health consequences.Summary. Background: Age at menarche has been used as a marker of environmental conditions during childhood. Previous work has shown trends of decreasing age at menarche throughout the 19th century, but reported trends in the 20th century have been less consistent. The nature of the relationship between age at menarche and adult life anthropometric measures may be important in understanding the importance of this measure on disease in later life. Aim: To establish whether mean age at menarche changed during the first half of the 20th century, and to determine the nature of associations between age at menarche and anthropometric measures in young adulthood. Subjects and methods: 3433 female students, who were born between 1919 and 1952 and who attended health checks at the student health service of the University of Glasgow between 1948 and 1968. Results: Mean age at menarche decreased from 13.2 years in the earliest born to 12.5 years in the latest born students. These results were not explained by changes in socio-demographic factors. Menarcheal age was positively associated with height and negatively associated with weight and BMI, results independent of socio-demographic and behavioural factors. Conclusions: The falling age at menarche described here may be related to nutritional influences in the first half of the 20th century. The influence of menarche on BMI in early adulthood may have important health consequences.

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 …

Body mass index in young adulthood and cancer mortality: a retrospective cohort study

Study objective: To examine the relation between body mass index (BMI) in young adulthood and subsequent mortality from cancer. Design: Cohort study. Setting: University of Glasgow student health service. Weight and height were measured by a physician, and used to calculate BMI. Participants: 8335 men and 2340 women who attended the student health service while at university between 1948 and 1968, and who were followed up with the NHS central register. Main results: The main outcome measure was cancer mortality. Three hundred and thirty nine men and 82 women died of cancer during the follow up (mean 41 years). BMI was associated with mortality from all cancers in men and women, although it did not reach conventional statistical significance. The adjusted hazard ratio (HR) (95% CI) per 5 kg/m2, was 1.22 (0.97 to 1.53) in men and 1.43 (0.95 to 2.16) in women. Two hundred men and 61 women died from cancers not related to smoking. The adjusted HR for mortality from these were 1.36 (1.02 to 1.82) and 1.80 (1.13 to 2.86) respectively. These results are adjusted for height, number of siblings, pulse rate, year of birth, age, smoking, birth order, number of siblings, and age at menarche in women. Site specific analyses, comparing the highest with the lowest quartile of the BMI distribution found increased risks of prostate cancer (n=28) and breast cancer among heavier subjects. No association between BMI and colorectal cancer was found. Conclusions: BMI in adolescence has lasting implications for risk of cancer mortality in later life. Future research will include measures of BMI throughout the lifecourse, to determine the period of greatest risk of obesity, in terms of cancer mortality.

Life course exposure and later disease: a follow-up study based on medical examinations carried out in Glasgow University (1948–68)

Evidence for the relationship between exposures in fetal life, infancy, childhood and early adulthood, and risk of chronic disease in later middle-age continues to accumulate. Further understanding of the associations between exposures acting over the life course and current morbidity and mortality in middle-age and later must depend upon the follow-up of previously established cohorts. This paper describes the design of, and background to, a follow-up of individuals who participated in a survey of student health in the University of Glasgow between 1948 and 1968. 15 332 students, almost a quarter of whom were female, had detailed medical information collected from a doctor-administered questionnaire and physical examination. Participation was voluntary; approximately 50% of the student population took part and these students were rep-resentative of the entire student population. Data collected include: socio-demographic, behavioural, developmental, anthropometric, and clinical details, as well as details of medical history and family health and structure. Data are over 95% complete for most variables. Over 40% of students were examined on two or more occasions with 1026 students (6.8%) having four or more examinations. Over 90% of students were from social classes I-III. Eighty-two per cent (12 533/15 322) of the students have been traced and flagged through the National Health Service Central Register and attempts are on-going to increase this figure. Those study members who have been traced are representative of the original cohort. To date 1111 (7.2%) of those traced have died. These data constitute a unique record of the health and physical development of a large cohort of students from Glasgow. Follow-up to investigate the relationship between indices of health and development, (height, weight, blood pressure), health behaviours and social circumstances in childhood and young adulthood, and mortality and morbidity in later adulthood is under way.

Changes in blood pressure among students attending Glasgow University between 1948 and 1968: analyses of cross sectional surveys

Abstract Objectives: To examine the changes in blood pressure over time in a cohort of young adults attending university between 1948 and 1968. Design: Cross sectional study. Setting: Glasgow University. Participants: 12 414 students aged 16-25 years—9248 men (mean age 19.9 years) and 3164 women (19.2 years)—who participated in health screening on entering university between 1948 and 1968. Main outcome measures: Systolic and diastolic blood pressure. Results: In male students mean systolic blood pressure adjusted for age decreased from 134.5 (95% confidence interval 133.8 to 135.2) mm Hg in those born before 1929 to 125.7 (125.0 to 126.3) mm Hg in those born after 1945, and diastolic blood pressure dropped from 80.3 (79.8 to 80.8) mm Hg to 74.7 (74.2 to 75.1) mm Hg. For female students the corresponding declines were from 129.0 (127.5 to 130.5) mm Hg to 120.6 (119.8 to 121.4) mm Hg and from 79.7 (78.7 to 80.6) mm Hg to 77.0 (76.5 to 77.5) mm Hg. Adjustment for potential confounding factors made little difference to these findings. The proportion of students with hypertension declined substantially in both sexes. Conclusions: Substantial declines in systolic and diastolic blood pressure over time were occurring up to 50 years ago in young adults who were not taking antihypertensive medication. Since blood pressure tracks into adult life, the results of the cross sectional comparisons suggest that factors acting in early life may be important in determining population risk of cardiovascular disease. Changes in such factors may have made important contributions to the decline in rates of cardiovascular diseases, particularly stroke, seen in developed countries during the past century. What is already known on this topic Mortality from stroke in developed countries decreased throughout the 20th century; declines in mortality from coronary heart disease occurred more recently Explanations may include favourable trends in risk factors, including blood pressure Since blood pressure tracks into adulthood, description of the trends occurring in blood pressure in young adults may help to elucidate the critical periods involved in influencing trends in blood pressure What this study adds Declines in blood pressure over time were taking place up to 50 years ago in young adults These changes did not result from use of antihypertensive medications and point to the importance of factors in early life in determining blood pressure and risk of subsequent cardiovascular disease

Associations of adult measures of childhood growth with breast cancer: findings from the British Women's Heart and Health Study

Since the two components of adult height – leg length and trunk length – are poorly correlated with each other and appear to be influenced by different early life factors, examining their separate influence on breast cancer may provide additional insights into the mechanisms responsible for the positive association between adult height and breast cancer. In a cross-sectional study of 4286 women aged 60–79 years, in whom there were 170 cases of breast cancer, we found total height, leg length and trunk length were all modestly positively and linearly associated with breast cancer. The magnitudes of the associations of leg and trunk length were similar: fully adjusted odds ratio (95% confidence interval) of breast cancer for a one standard deviation (s.d.) increase in leg length 1.17 (0.98, 1.39) and for a 1 s.d. increase in trunk length 1.19 (0.99, 1.41). Self-reported birth weight (available on 33% of the sample) was positively and linearly associated with breast cancer: fully adjusted odds ratio of breast cancer for a 1 s.d. increase in birth weight 1.30 (0.93, 1.80). These associations were all independent of each other and other potential confounding factors and are likely to reflect different mechanisms by which factors operating prenatally and prepubertally influence breast cancer risk.

Is maternal transmission of coronary heart disease risk stronger than paternal transmission

Objective: To test whether intergenerational transmission of coronary heart disease (CHD) to offspring is greater from the mother than from the father, the association between parental history of CHD and coronary mortality in male offspring was examined. Design: Prospective cohort study with 43 years of follow up. Setting: University of Glasgow. Participants: Male students (n = 8402) aged 16–30 years when examined in 1948 to 1968. Main outcome measure: Fatal CHD. Main results: Of the 8402 men studied, 615 (7.3%) reported a history of CHD in at least one of the parents: 479 (5.8%) for fathers only, 124 (1.6%) for mothers only, and a further 12 (0.2%) for both their parents. During follow up, 373 (4.4%) men died of CHD. Parental history of disease was associated with fatal CHD and controlling for personal risk factors such as cigarette smoking, body mass index, systolic blood pressure, and father’s social class did not attenuate this relation. The fully adjusted hazard ratios were 1.53 (95% confidence interval (CI) 1.08 to 2.18), 1.19 (95% CI 0.61 to 2.32), and 8.65 (95% CI 2.65 to 28.31) for father only, mother only, and both parents with CHD, respectively, compared with men whose parents did not have CHD. There was some evidence for interaction between parental histories (p = 0.049), with particularly high risk if both parents reported a history of CHD. Conclusions: This study found no differential transmission of CHD. Paternal history of CHD was at least as important as maternal history. Data from other comparable cohorts provide no consistent evidence of differential transmission. Intergenerational transmission of CHD does not appear to have differential effects between mothers and fathers.