C. E. D. Chilvers

A case-control study of oesophageal adenocarcinoma in women: a preventable disease

The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case–control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of adenocarcinoma of the oesophagus, and 74 female controls matched by age and general practice. High body mass index (BMI) around the age of 20 years (highest vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI) 1.28–28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR = 0.08, 95% Cl 0.01–0.49) were associated with increases in risk. Breastfeeding by women was associated with reduced risk of their subsequently developing this cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20–0.82) and there was a significant dose–response effect with total duration of breastfeeding. The summary population attributable risk from these three factors was 96% (90% if breastfeeding is excluded). We conclude that high BMI in early adulthood and low consumption of fruit are important risk factors for adenocarcinoma of the oesophagus. Breastfeeding may confer a protective effect but this needs confirmation. This cancer is a largely preventable disease in women.

Cigarette Smoking, Alcohol and Caffeine Consumption, and Bone Mineral Density in Postmenopausal Women

Abstract: The aim of this analysis was to compare the effects of different measures of cigarette, alcohol and caffeine consumption upon bone mineral density (BMD). Five hundred and eighty postmenopausal women aged 45–59 years at recruitment completed a risk factor questionnaire that contained detailed sections on cigarette, alcohol and caffeine consumption. BMD was measured using dual-energy X-ray absorptiometry. Measurements taken at five bone sites were used: anterior-posterior spine, femoral neck, greater trochanter, radius/ulna and whole body. The data were analyzed using multiple linear regression, adjusting for a number of established BMD risk factors. BMD was more strongly related to the number of months spent smoking than to pack-years of smoking at all five sites (p <0.05 at four of the five sites). There were significant reductions in BMD when comparing smokers with non-smokers at ages 20, 30 and 40 years, but not for current smoking. Lifetime alcohol consumption and current alcohol consumption did not have an independent association with BMD. However, the heaviest beer drinkers in the sample had a particularly low bone density. Caffeine consumption at various ages was not associated with BMD. The results of these analyses suggest that for predicting BMD a simple history of smoking duration is as good as trying to obtain more detailed smoking information, but that only 25% of the variation in BMD is explained by personal characteristics, family history and lifestyle factors.

Risk factors for squamous cell carcinoma of the oesophagus in women: a case–control study

Oesophageal cancer rates in women in the UK are more than 3 times higher than in most other European populations. A population-based matched case–control study of histologically confirmed squamous cell carcinoma of the oesophagus in women was carried out in 4 regions in England and Scotland. Interviews were carried out in hospital or at home and topics included: smoking; alcohol; tea and coffee consumption; medical and obstetric history; and diet. Response rates were 62% for cases and 65% for first-chosen controls. There were 159 case–control pairs. Significant results were found for: eating salads (odds ratio (OR) 0.42, 95% CI 0.20–0.92 in the highest quartile of consumption) and a light (as distinct from no) breakfast (OR 0.18, 95% CI 0.07 – 0.48) were protective; quantity of tea was a risk factor and there was a significant positive trend with temperature at which hot drinks were consumed (P = 0.03). Alcohol consumption was unrelated to risk, but there was a significant trend with years of smoking (P = 0.015). A protective effect of aspirin consumption was confined to the English centres (OR 0.08, 95% CI 0.01–0.56). Comparison with a parallel study of adenocarcinoma indicated a common protective effect of a healthy diet but otherwise distinct risk factors.

Risk factors for testicular germ cell tumours by histological tumour type

SummaryThere are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology.

Reproductive, Menstrual and Menopausal Factors: Which Are Associated with Bone Mineral Density in Early Postmenopausal Women?

The associations between a number of reproductive and menopausal factors and bone mineral density (BMD) were studied in a sample of early postmenopausal women. The study included 580 women aged 45–61 years who completed a risk factor questionnaire containing sections on obstetric and menstrual history. BMD measurements were taken at the anteroposterior (AP) spine, greater trochanter, femoral neck, total radius and whole body, along with whole body bone mineral content (BMC). In analyses adjusting for key confounders, number of pregnancies was more strongly associated with increased BMD than number of live births at all sites (p<0.05 at femoral neck and total radius), and menstrual years was more strongly associated with increased BMD than years since menopause (p<0.05 at all sites). Hysterectomized women had a significantly higher adjusted mean BMD than non-hysterectomized women at all sites (AP spine: 0.999 g/cm2 vs 0.941 g/cm2, p<0.001), although there were no significant differences in BMD between hysterectomized women who had a bilateral oophorectomy and those whose ovaries were preserved. Negative associations between the duration of hot flushes and BMD were statistically significant (p<0.05) at the three non-hip sites. In multiple regression analyses containing all reproductive terms, duration of hormone replacement therapy (HRT) use, menstrual years and hysterectomy status were significantly associated with BMD at all five sites, whilst oral contraceptive use before the age of 23 years was significantly associated with increased BMD at all sites except the total radius. Breastfeeding duration, the duration of oral contraceptive use and premenopausal amenorrhea were found to have no association with BMD. Results for whole body BMC were consistent with those for the five BMD sites, across all the variables considered here. These findings confirm the importance of HRT use and duration of menses as predictors of BMD, whilst the results for hysterectomy status and early oral contraceptive use require further consideration.

Maternal risk factors for testicular cancer: a population-based case-control study (UK)

AbstractObjective: To investigate the role of a range of maternal and pre-natal characteristics as potential risk factors for testicular cancer. Methods: A population-based case–control study of testicular cancer. Mothers of participants completed a questionnaire about their reproductive and obstetric history. Results: The risk of testicular cancer was approximately doubled for sons of mothers aged 15–19 years at conception compared with mothers with older ages at conception. Nausea or vomiting during the first trimester of pregnancy was associated with a reduced risk of testicular cancer (odds ratio of 0.73, 95% confidence interval 0.53–1.00). There was also a borderline reduction in risk in men who had been breastfed for 6 months or more (odds ratio 0.65, 95% confidence interval 0.41–1.04). Men who had low birthweights (2500 g) or had been born two or more weeks early had slightly increased risks, as did men whose mothers had used oral contraception in the 12 months before their conception. Conclusions: These findings support previous reports of increased risks in men born early or with low birthweight, but the direction of the association with maternal age is contrary to some other studies. The suggestion of a protective effect of breastfeeding requires further confirmation.

The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation

Summary.  Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview‐based case–control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged ≤75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age‐ and sex‐matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2·51, 95% confidence interval (CI) 1·02–12·01], particularly for woodworm treatment (OR = 5·1, 95% CI 1·5–17·4). This study identified significant risks associated with self‐reported exposure to solvents, radiation and pesticides in the workplace. Self‐reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.

Depot medroxyprogesterone acetate and breast cancer : A review of current knowledge

SummaryDepot medroxyprogesterone acetate (DMPA) has been used worldwide since 1964 as a contraceptive and by 1993 was in use in more than 90 countries. It was licensed for contraceptive use in the US in 1992. One of the reasons for this delay in licensing in the US was the possibility of an increased risk of breast cancer associated with its use.A pooled analysis has recently been published, which brings together the data from 2 large studies of breast cancer risk associated with DMPA use. The overall results are reassuring, but there is some evidence of an increased risk of breast cancer associated with recent use of DMPA.There are substantial difficulties in interpreting this increase in risk. It is certainly possible that it may be the result of surveillance bias, although it could be a short term increase in risk that is not in fact sustained.The conclusion that DMPA should not be restricted as a contraceptive, provided that appropriate advice is given before use, is well-founded. However, further epidemiological work is needed on the long term effects of DMPA.

Counseling versus antidepressant therapy for the treatment of mild to moderate depression in primary care economic analysis

OBJECTIVE To compare the cost-effectiveness of generic psychological therapy (counseling) with routinely prescribed antidepressant drugs in a naturalistic general practice setting for a follow-up period of 12 months. METHODS Economic analysis alongside a randomized clinical trial with patient preference arm. Comparison of depression-related health service costs at 12 months. Cost-effectiveness analysis of bootstrapped trial data using net monetary benefits and acceptability curves. RESULTS No significant difference between the mean observed costs of patients randomized to antidepressants or to counseling (342 pounds sterling vs 302 pounds sterling , p = .56 [t test]). If decision makers are not willing to pay more for additional benefits (value placed on extra patient with good outcome, denoted by K, is zero), then we find little difference between the treatment modalities in terms of cost-effectiveness. If decision makers do place value on additional benefit (K > 0 pounds sterling), then the antidepressant group becomes more likely to be cost-effective. This likelihood is in excess of 90% where decision makers are prepared to pay an additional 2,000 pounds sterling or more per additional patient with a good global outcome. The mean values for incremental net monetary benefits (INMB) from antidepressants are substantial for higher values of K (INMB = 406 pounds sterling when K = 2,500 pounds sterling). CONCLUSION For a small proportion of patients, the counseling intervention (as specified in this trial) is a dominant cost-effective strategy. For a larger proportion of patients, the antidepressant intervention (as specified in this trial) is the dominant cost-effective strategy. For the remaining group of patients, cost-effectiveness depends on the value of K. Since we cannot observe K, acceptability curves are a useful way to inform decision makers.

Association between a family history of fractures and bone mineral density in early postmenopausal women

The aim of this analysis was to measure the strength of the association between a family history of fractures and bone mineral density (BMD), and to determine what definition of family fracture history best predicts BMD. Five hundred and eighty postmenopausal women aged 45-59 at recruitment completed a risk factor questionnaire. Women were asked to recall details of fractures sustained by any female relative. BMD measurements taken at five sites were used. The data were analysed using linear regression, adjusting for age. Two hundred and ninety-seven (52.8%) women reported a family history of fractures, and they had a significantly lower BMD at two of the sites measured (p < 0.05). The associations with BMD were most significant when only counting fractures that occurred in the subjects mother or a sister as a result of low trauma, with no restrictions made on age at the time of fracture and site of fracture (p < 0.01 at three sites; 0.01 < p < 0.05 at two sites). Women with a family history according to this definition had a 4.6% reduction in BMD at the femoral neck. When T scores were used to categorize women as either osteopenic/osteoporotic (T < -1) or normal at the femoral neck, the sensitivity of using this definition was 39% and the specificity was 74%. The small group of women that reported a low-trauma hip fracture in a mother or sister (n = 23) had a mean femoral neck BMD which was 8.9% lower than that of the remainder of the sample, although this difference was less statistically significant than when low trauma fractures at any site were counted. Of these 23 women, 70% were osteopenic or osteoporotic, compared with 57% of those reporting a low-trauma fracture at any site and 47% of the sample as a whole. The sensitivity of this definition, however, was low (6%). From these analyses it can be concluded that the definition of family fracture history that best predicts BMD in postmenopausal women is a fracture at any age in a mother or sister resulting from low trauma, although the sensitivity and specificity of using a family history of fractures by itself to screen for low BMD were poor.