Margaret Booth

Risk factors for ovarian cancer: a case-control study.

A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983. Menstrual characteristics, reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls. High gravidity, hysterectomy, female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer. Infertility and late age at menopause were associated with an increase in risk. While these factors were related, they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors.

Human papillomavirus and invasive cervical cancer in Brazil

A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer.

Mortality of employees of the Atomic Weapons Establishment, 1951-82.

A total of 22,552 workers employed by the Atomic Weapons Establishment between 1951 and 1982 were followed up for an average of 18.6 years. Of the 3115 who died, 865 (28%) died of cancer. Mortality was 23% lower than the national average for all causes of death and 18% lower for cancer. These low rates were consistent with the findings in other workforces in the nuclear industry and reflect, at least in part, the selection of healthy people to work in the industry and the disproportionate recruitment of people from the higher social classes. At some time during their employment 9389 (42%) of the workers were monitored for exposure to radiation, the average cumulative whole body exposure to external radiation being 7.8 mSv. Their mortality was generally similar to that of other employees, even when exposures were lagged by 10 years. The rate ratio after a 10 year lag in workers with a radiation record compared with other workers was 1.01 (95% confidence interval 0.92 to 1.10) for all causes of death and 1.06 (0.89 to 1.27) for all malignant neoplasms. The only significant differences were for prostatic cancer (rate ratio 2.23; 95% confidence interval 1.13 to 4.40) and for cancers of ill defined and secondary sites (rate ratio 2.37; 1.23 to 4.56). Cancers of lymphatic and haemopoietic tissues were notable for their low occurrence in the study population, with only four deaths from leukaemia and two from multiple myeloma in workers with a radiation record, 9.16 and 3.55 deaths respectively being expected on the basis of national rates. Among workers who had a radiation record 3742 (40%) were also monitored for possible internal exposure to plutonium, 3044 (32%) to uranium, 1562 (17%) to tritium, 638 (7%) to polonium, and 281 (3%) to actinium. In these workers mortality from malignant neoplasms as a whole was not increased, but after a 10 year lag death rates from prostatic and renal cancers were generally more than twice the national average, these excesses arising in a small group of workers monitored for exposure to multiple radionuclides. Though mortality from lung cancer in workers monitored for exposure to plutonium was below the national average, it was some two thirds higher than in other radiation workers, the excess being of borderline statistical significance. Mortality from malignant neoplasms as a whole showed a weak and non-significant increasing trend with increasing level of cumulative whole body exposure to external radiation. When the exposures were lagged by 10 years the trend became stronger and significant, the estimated increase in relative risk per 10 mSv being 7.6% (95% confidence interval 0.4% to 15.3%). This trend was confined almost entirely to workers who were also monitored for exposure to radionuclides (p<0.001), the main contributions coming from lung cancer and prostatic cancer. Exposures of the lung and prostate from internal sources of radiation were not quantified, except for the contribution from tritium. It was therefore not possible to assess the extent to which the associations were due to internally deposited radionuclides rather than external exposure. The finding for prostatic cancer taken in conjunction with the results of other studies suggest a specific occupational hazard in a small group of workers in the nuclear industry who had comparatively high exposures to external radiation and who were also monitored for internal exposure to multiple radionuclides. Research is needed to discover whether any of the radionuclides and other substances concerned are concentrated in the prostate. The occurrence of lung cancer in this workforce requires further investigation taking into account smoking habits and tissue doses from inhaled radionuclides.

Cancer mortality and morbidity in employees of the United Kingdom Atomic Energy Authority, 1946-86.

In further analyses of a cohort of 39,718 United Kingdom Atomic Energy Authority employees after 7 more years follow-up, cancer mortality, based on 1,506 deaths in 1946-86, was 20% below the national average. Prostatic cancer mortality showed a statistically significant association with external radiation exposure, largely confined to men who were also monitored for internal contamination by radionuclides other than plutonium. Prostatic cancer mortality was highest in radiation workers at Winfrith. In women monitored for radiation exposure, mortality from cancer of the uterus (including the cervix uteri) was increased relative to other employees, and, showed a statistically significant association with external radiation exposure. While there were some other statistically significant results, as would be expected by chance alone when multiple comparisons are made, there were no other cancer sites with consistently exceptional findings. Point estimates for risk associated with increasing exposure to radiation suggest a decrease of four deaths per 10(4) person-years per Sv for leukaemia and an increase of 20 deaths for all cancers except leukaemia, but confidence intervals indicate that a wide range of values are compatible with the data. Cancer morbidity based on 1,699 registrations in 1971-84 was 12% below the national average. Findings from site-specific analyses largely replicated those of the mortality analyses.

Side effects of danazol compared with an ethinyloestradiol/norgestrel combination when used for postcoital contraception.

A postcoital contraceptive with a lower incidence of nausea and vomiting than oestrogen-progestogen combinations would be a significant advance. During a nine-month period, 101 women were treated at the Margaret Pyke Centre in London with either an oestrogen-progestogen combination or with danazol. A comparison of the side effects of each drug is reported. Those treated with danazol were six times less likely to experience nausea and none vomited. With the exception of breast symptoms, other side effects were five times less common in women receiving danazol. These differences give danazol a clear advantage in terms of patient acceptability. Further experience will enable the efficacy of danazol to be evaluated and so determine whether this drug should become the preferred hormonal postcoital treatment.

A case-control study of benign ovarian tumours.

STUDY OBJECTIVE--The aim was to investigate the association between reproductive, contraceptive, and menstrual factors and risk of benign ovarian tumours. DESIGN AND SETTING--This was a case-control study carried out in six London Hospitals. An interviewer administered questionnaire was used. SUBJECTS--62 women with a benign epithelial ovarian neoplasm, 37 women with a functional ovarian cyst, and 20 women with a dermoid cyst presenting between 1983 and 1985, together with 132 controls, took part in the study. MAIN RESULTS--On average, women with a benign epithelial ovarian neoplasm were older than those with a functional ovarian cyst, who in turn were older than those with a dermoid cyst. Nulliparity and infertility were associated with an increased risk, and multiparity with a reduced risk, of benign epithelial ovarian neoplasms. Infertility and pelvic inflammatory disease were associated with increased risks of functional and dermoid cysts. Recent use of oral contraceptives was associated with a reduced risk of all three tumour types. CONCLUSIONS--The findings suggest that the aetiology of ovarian cysts and benign epithelial ovarian neoplasms may differ. The aetiology of benign and malignant epithelial ovarian neoplasms may be similar, however, since some risk factors are shared.

Health related selection and death rates in the United Kingdom Atomic Energy Authority workforce.

Follow up data on 37,355 employees of the United Kingdom Atomic Energy Authority (UKAEA) for the period 1946-79 were analysed to investigate the extent to which selection for work on the basis of health affected subsequent death rates. Causes of death were grouped into two broad categories for analysis: all cancers and all other causes of death. Evidence for an effect of selection of healthy individuals into the workforce was sought primarily by examining standardised mortality ratios (SMRs) by period since recruitment. SMRs for both categories were particularly low during the first two years after recruitment (SMR = 69, 95% confidence interval (CI) 48-97 for all cancers; SMR = 55, 95% CI 44-69 for all other causes of death). SMRs for all cancers did not increase significantly with period since recruitment (chi 2 for trend = 0.4, p = 0.53) but did increase for causes of death other than cancer (chi 2 for trend = 11.1, p = 0.001). Although adjustment for social class strengthened the association between death from causes other than cancer and period since recruitment (chi 2 for trend = 18.8, p less than 0.001), simultaneous adjustment for all confounding factors considered (age at death, sex, calendar period of death, geographical location of the workforce, and social class) produced results broadly similar to those obtained from the unadjusted analyses for both cause of death categories. SMRs remained low even after 25 years of follow up (SMR = 84, 95% CI 69-101 for all cancers; SMR = 81, 95% CI 72-91 for all other causes of death). The persistently low SMRs observed in this workforce are unlikely to be due to the selection of healthy individuals at the time of recruitment but may be due to differences in sociodemographic and lifestyle characteristics. The effect on mortality of selection of individuals out of the workforce due to ill health was also examined. SMRs were particularly high for both categories in the first two years after termination of employment in individuals who left before normal retirement age (SMR = 167, 95% CI 131-211 for all cancers; SMR = 149, 95% CI 128-173 for all other causes of death). In comparison, death rates for the subsequent three years after termination of employment were lower (SMR = 89, 95% CI 67-115 for all cancers, SMR = 99, 95% CI 85-115 for all other causes of death). The persistently low SMRs observed in this workforce are unlikely to be due to the selection of healthy individuals at the time of recruitment but may be due to differences in sociodemographic and lifestyle characteristics. The effect on mortality of selection of individuals out of the workforce due to ill health was also examined. SMRs were particularly high for both categories in the first two years after termination of employment in individuals who left before normal retirement age (SMR = 167, 95% CI 131-211 for all cancers; SMR 149,95% CI 128-173 for all other causes of death). In comparison, death rates for the subsequent three years after termination of employment were lower (SMR = 89, 95% CI 67-115 for all cancers SMR = 99, 95% CI 85-115 for all other causes of death). Apart from this initial fall, there was little evidence of a systematic increase or decrease in mortality with increasing period was not significantly associated with durationof employment for either cause of death category either before or after adjustment for confounding factors. Whereas selection of individuals into or out of the workforce on the basis of health affects the way in which death rates change with time, other factors such as sociodemographic characteristics or health related behaviour determine the general level of mortality in the longer run. The persistently low SMRs observed in this workforce throughout the follow up period suggest that selection on the latter factors are likely to have had a considerable effect on death rates in the UKAEA workforce.

Behavioural patterns in women requesting postcoital contraception.

In a sample of women presenting for postcoital contraception in central London, 2 main categories of women were apparent. The 1st comprised those having regular intercourse: the majority of these had experienced a contraceptive method failure. Many of the 2nd category had used no contraceptive; they were often having intercourse for the 1st or 2nd time with a new partner, for the 1st time after an interval with an existing partner or for the 1st time ever. Many women had experienced difficulty in finding out where they could be treated but were persistent in their efforts to obtain the necessary expert advice. Almost all had used contraception in the past. Acceptance of a contraceptive method for future use was high.