Biomedical subjects
D C Skegg
Publications and source records attributed to D C Skegg.
Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies.
BACKGROUND: Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. DESIGN: Pooled results from two case-control studies. SETTING: New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). PARTICIPANTS: A total of 1768 women with breast cancer and 13,905 controls, most of whom were younger than 55 years. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer in women who had used DMPA. RESULTS: The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). CONCLUSIONS: The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use.
Oral contraceptive use and risk of breast cancer in older women (New Zealand).
The effect of oral contraceptive (OC) use at older ages on the risk of breast cancer was examined in a national population-based case-control study conducted in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer, and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk (RR) of breast cancer for women aged 45 to 54 years at diagnosis who had ever used OCs was 1.0 (95 percent confidence interval [CI] = 0.77-1.3). There was no significant increase in risk of breast cancer among recent users of OCs of any age. Analyses according to age at first and last use among women aged 40 years and older at diagnosis showed no group with an elevated risk of breast cancer. Women who had used OCs for 10 years or longer after age 40 had an apparent increase in risk (RR = 2.7, CI = 0.97-7.5), but the trend in risk with duration of use was not significant. These findings suggest that OC use in older women does not affect their risk of breast cancer appreciably, but it is not possible to rule out a modest increase in risk with such use.
Risk assessment issues in breast cancer.
Breast cancer is the most common malignancy affecting women, and its incidence has been increasing in many countries. The aetiology of breast cancer is poorly understood, so there is concern as to which factors in our environment or lifestyle are responsible for the increase. There is a need for reliable risk assessment, which involves the steps of hazard identification, hazard evaluation, exposure evaluation and risk estimation. Short-term laboratory tests and long-term tests in animals are useful for priority-setting, but quantitative human risk assessment should preferably involve observations of humans. Epidemiological studies vary in the degree of reliance that can be placed on their results. The main types of epidemiological investigation are illustrated by recent examples from the literature on breast cancer. Careful judgement is required in assessing whether any association between a factor and a disease is likely to be causal. The injectable contraceptive, depot medroxyprogesterone acetate (DMPA, 'Depo-Provera'), has been controversial because it caused malignant mammary tumours in beagle dogs. Two recent case-control studies found no overall association between DMPA and the risk of breast cancer in women. There was some evidence of increased risk in certain sub-groups of women, which could be interpreted with more confidence if there were a better understanding of the biology of human breast cancer. Nevertheless, the results do not support the prediction from beagle experiments that DMPA might increase the overall risk of breast cancer.
Cancer incidence in England and Wales and New Zealand and in migrants between the two countries.
Risks of cancer incidence in people born in England and Wales and New Zealand (non-Maoris) living in their home countries, and after migration between the two countries, were analysed using data from their national cancer registries. Since these populations are of similar genetic origin, any real differences in cancer incidence between them are likely to reflect the action of environmental or behavioural risk factors. The greatest differences in risk between the countries were for cutaneous melanoma and lip cancer. In each sex, relative risks of these malignancies were 4 or greater for the New Zealand-born in New Zealand compared with English and Welsh natives in their home country, and risks for migrants in each direction were generally intermediate between those born in the home country in the two countries. Sizeable significantly raised risks in the New Zealand-born in New Zealand compared with English and Welsh natives in England and Wales also occurred for cancers of the mouth, small intestine, colon, thymus, eye and thyroid, and non-Hodgkin's lymphoma in each sex, and for cancer of the prostate. For all of these sites except mouth, small intestine and colon there were also risks around or above New Zealand-born levels for English and Welsh migrants to New Zealand; for colon cancer these migrants had risks close to those in England and Wales. New Zealand migrants to England and Wales had risks of cancers of the colon and prostate that were similar to or above New Zealand levels. Risks of cancers of the stomach, lung, pleura and bladder, and Hodgkin's disease in each sex, and cancers of the cervix, ovary and scrotum and penis, were substantially and significantly lower in the New Zealand-born living in New Zealand than in English and Welsh natives in England and Wales. In English and Welsh migrants to New Zealand risks of bladder cancer in each sex, and of scrotal and penile and pleural cancer in males, approximated to England and Wales risks; cervical cancer risk approximated to the New Zealand risk; and stomach, lung and ovarian cancers showed intermediate risks. Migrants from New Zealand to England and Wales did not gain the lung cancer or clearly the stomach cancer risk of their host country, but did have bladder cancer risks approximating to those in England and Wales.(ABSTRACT TRUNCATED AT 400 WORDS)
Monthly combined injectable contraceptives and neoplasia.
Monthly injectable contraceptives, containing a combination of a long-acting progestogen and an estrogen, have been used in Latin America and China for many years. While knowledge about the effects of other hormonal contraceptives on cancer risk is relevant, close analogies with monthly injectables cannot be made. The relation between use of these preparations and cancers of the breast and cervix has been examined in case-control studies, but no firm conclusions can be drawn because of limitations in sample size. Adequate studies of the influence of monthly injectable contraceptives on risk of neoplasia need to be carried out.
HIV surveillance by testing saliva from injecting drug users: a national study in New Zealand.
OBJECTIVE: To determine whether the prevalence of HIV infection among injecting drug users in New Zealand has remained low since the introduction of a needle and syringe exchange scheme in May 1988. DESIGN: Anonymous survey of intravenous drug users attending outlets of the exchange scheme, based on questionnaires and saliva testing. SETTING: Twelve pharmacies and community outreach organisation in six cities. SUBJECTS: Altogether 620 people provided saliva specimens and completed questionnaires. These represented 73% of those who visited exchange scheme outlets during a three month period in 1992. MAIN OUTCOME MEASURE: Saliva was tested for antibodies to HIV-1 and HIV-2 using an IgG-capture enzyme linked immunosorbent assay (GACELISA). RESULTS: Of 591 specimens eligible for inclusion, only three (0.5%) were repeatedly reactive in the GACELISA test, while two of these were also positive in a Western blot test. CONCLUSIONS: Although surveys show that sharing of needles and syringes was common in New Zealand until recently, the prevalence of HIV infection in intravenous drug users has remained low. This can probably be attributed to the success of educational campaigns and legislative action to allow a needle and syringe exchange scheme to be set up.
Cervical smear histories of Maori women developing invasive cervical cancer.
AIMS: To locate problems with the implementation of cervical screening for Maori women by investigating the histories of women with invasive cervical cancer, and determining why their disease had not been detected by screening and treated at an intraepithelial stage. METHODS: In a national study, the screening histories of 46 Maori women with invasive cervical cancer were ascertained by interview and from hospital, general practitioner and cytology laboratory records. RESULTS: Possible reasons for failure of cervical screening were never having had a smear (54%), infrequent smear tests (22%) and previous abnormal smears without appropriate follow-up (4%). Only six women (13%) had one or more normal smears in the three years before diagnosis. CONCLUSIONS: The main factor underlying the onset of invasive cancer was an absence of cervical screening or infrequent smear tests. Although no slide review was done, false negative reporting could have been a factor in only a small number of cases. Ways need to be found to encourage Maori women to be screened and to recall women regularly.
Unlinked anonymous monitoring of HIV prevalence at sexually transmitted disease clinics.
AIM: To determine the prevalence of HIV infection among patients attending the four sexually transmitted disease (STD) clinics in two metropolitan areas of New Zealand. METHODS: The population studied comprised everyone who attended between August 1991 and August 1992 because of concern about a possible new episode of an STD and who had a blood specimen taken for hepatitis B (or syphilis) serology. The study involved unlinked anonymous testing of left-over blood specimens, following ethical guidelines that have been proposed internationally. RESULTS: Among 8478 specimens tested, 23 (2.7 per 1000) were found to be HIV positive. The seroprevalence rates per 1000 among women, heterosexual men, and homosexual or bisexual men were 1.1, 1.3, and 44, respectively. All but five of the infected people were either known to be HIV positive or had an identifiable test during their clinic attendance. CONCLUSIONS: The seroprevalence rates are similar to those reported from STD clinics in England, and suggest that heterosexual transmission of HIV infection has not yet been extensive in New Zealand.
Vasectomy and risk of cancers of prostate and testis.
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Variation and covariates of the number of benign nevi in adolescents.
Melanocytic nevi of diameter greater than or equal to 2 mm were counted on most of the skin surface of 349 adolescents aged 14-15 years of European race or ethnicity in Dunedin, New Zealand. Total counts are described by means of a form of Poisson-error log-linear modeling suitable for data showing unexplained variation (NE Breslow, Appl Statist 1984;33:38-44). There were marked interpersonal variation in the number of nevi; only some was attributable to observed factors. The mean and median counts were 23.8 and 18 nevi, respectively. The estimated ratio of the number of nevi for females compared with males was 0.7 (95% confidence interval (CI) 0.6-0.8). Greater amounts of sunbathing were associated with greater numbers of nevi. Hair and eye color, socioeconomic status, and sunburn history did not show statistically significant effects. Time since menarche and shaving status also showed no effects. Lack of suntan was associated with lower counts. Freckling was positively correlated with higher counts; the severe freckling group had an estimated ratio of 1.9 (95% CI 1.3-2.8) compared with those with no or very few freckles. The results are consistent with the hypothesis that ultraviolet radiation exposure from recreational sun exposure positively influences the total burden of nevi in normal subjects. Comparison with other epidemiologic studies suggests that the typical ultraviolet radiation dose-nevus yield curve might be steeper in males than females. Unexplained variation of nevus count may reflect heterogeneity of constitutional factors not yet measured in epidemiologic studies.
Projections of cervical cancer mortality and incidence in New Zealand: the possible impact of screening.
STUDY OBJECTIVE: The aim was to estimate the likely burden of cervical cancer in New Zealand over the next two decades, according to whether cervical screening services are made more effective. DESIGN: The study was based on national mortality and incidence data for the periods 1954-87 and 1954-86, respectively. An age-period-cohort model was used to estimate the contributions of age, time period, and birth cohort effects to the occurrence of cervical cancer. Using age specific estimates of the future female population of New Zealand, projections of cervical cancer mortality and incidence until the year 2008 were derived from the model. Projections were made assuming either that screening services will not be improved, or that an immediate improvement in the organisation of screening will lead to a decline in period effects for incidence of 15% per five year time period (with a slightly delayed effect on mortality). It was also assumed either that the risk in new birth cohorts will be similar to that in recent cohorts, or that their risk will be halved as a result of changes in sexual behaviour (due to education about AIDS or other factors). Combining these assumptions produced four sets of estimates, reflecting a range of possible scenarios. SETTING: Both the data used and the projections obtained related to the entire population of New Zealand women. MAIN RESULTS: For both mortality and incidence, projections were made of age specific rates, cumulative rates, and absolute numbers of deaths or new cases. With the first assumption about new birth cohorts, it was estimated that both mortality and incidence rates will increase if screening services are are not improved. In absolute terms, the present 100 deaths per year could increase to about 148 deaths per year, while there could be a much larger increase in incidence from 235 per year to about 440 per year). With improved screening, there could be a reduction in age specific mortality rates and a modest decline in the number of deaths, while a reduction in incidence rates would be accompanied by about the same number of new cases as at present. In comparison with improvements in screening, changes in the underlying risk in new birth cohorts would have much smaller effects on the occurrence of cervical cancer over the next two decades. CONCLUSIONS: Plausible improvements in cervical screening are likely to be accompanied by only small changes in the burden of cervical cancer over the next two decades. If screening services are not improved, however, there will be striking increases in both mortality and incidence.
Alcohol consumption and risk of breast cancer.
In a national case-control study, 891 New Zealand women aged 25 to 54 with newly diagnosed breast cancer were compared with 1,864 control subjects selected at random from the electoral rolls. The relative risk of breast cancer for current drinkers of alcohol, compared with women who had never drunk alcohol, was 1.0 (95% confidence interval 0.64 to 1.7). For ex-drinkers the relative risk was 1.3 (95% confidence interval 0.74 to 2.5). Women drinking up to 14 drinks per week had no increase in risk, while the relative risk in those consuming more than 14 drinks per week was 1.8 (95% confidence interval 0.87 to 3.8). There was no evidence of effect modification by age at diagnosis, menopausal status, body mass index, or any of the other variables examined. While these results provide little support for the hypothesis that moderate alcohol consumption increases the risk of breast cancer, they are not inconsistent with the weak associations that have been found in many other studies. Possible explanations for such a relationship are considered.
Occurrence of AIDS in New Zealand: the first seven years. MRC AIDS Epidemiology Group.
The 179 people in New Zealand with AIDS diagnosed up to the end of 1989 and notified by 30 June 1990 are reviewed. Retrospective data collection provided the first available information on date of diagnosis, ethnic affiliation, district of usual residence, and survival. Of the 179 people with AIDS, 173 were male. AIDS occurred most commonly between the ages of 30 and 50, but there were two children under 10. The standardised cumulative incidence rates (per 100,000) in the European, Maori, and Pacific Island populations were 5.3, 4.5, and 5.5, respectively. The majority affected (154) were men who had had sexual contact with men. Three of five intravenous drug users also reported such contact. Smaller numbers were presumed to have been infected through heterosexual contact (7), treatment of haemophilia (3), blood transfusions (2), or perinatally (1). In seven cases the mode of transmission was unknown. The proportion of people who had been living overseas when first diagnosed was initially high but declined, so that 134 were known to have been diagnosed in New Zealand. Of these, 107 lived in Auckland or Wellington. Survival analysis using the Kaplan-Meier method showed that the median time from diagnosis to death was 58 weeks.
Multiple sclerosis: nature or nurture?
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Oral contraceptives and neoplasia: an introduction.
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A feasibility study of organised cervical screening in southern New Zealand.
The 1985 electoral roll was used as a register to invite 1013 women to participate in a screening program. Appointment times and a choice of venues for having a smear were not provided. Overall, 26 per cent of the women sent invitations registered with the program. After adjustment for the prevalence of hysterectomy, the proportion who registered with the program was about 32 per cent. The low level of registration and difficulties experienced in tracing registrants and nonregistrants over time using the electoral roll resulted in the cessation of the program after 3 years. An assessment of the original invitation was made using a small case-control study, and associations between the screening history stated at interview and screening over the duration of the program were examined in nonregistrants.
Oral contraceptives and risk of breast cancer.
A national population-based case-control study was conducted in New Zealand to assess the effects of hormonal contraception on breast-cancer risk. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk of breast cancer for women who had ever used oral contraceptives was 1.0 (95% confidence interval 0.82-1.3). There was no increase in risk with duration of use, even among women who had continued to use oral contraceptives for 14 or more years (relative risk = 1.1, 95% confidence interval 0.78-1.7). The risk of breast cancer was not increased by use of oral contraceptives for long periods before the first pregnancy or by starting use at a young age. Parity, age at menarche, family history of breast cancer, or history of benign breast disease did not modify the effect of oral contraceptives on breast-cancer risk. Relative risk estimates were slightly, although not significantly, increased during the first few years after starting oral contraception and in women under 35 years of age at diagnosis.