Melbourne School of Population and Global Health - Research Publications
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ItemAssociations between congenital malformations and childhood cancer. A register based case-control study(CHURCHILL LIVINGSTONE, 1998-11)This report describes a population-based case-control study that aimed to assess and quantify the risk of children with congenital malformations developing cancer. Three sources of data were used: the Victorian Cancer Register, the Victorian Perinatal Data Register (VPDR) and the Victorian Congenital Malformations/Birth Defects Register. Cases included all Victorian children born between 1984 and 1993 who developed cancer. Four controls per case, matched on birth date, were randomly selected from the VPDR. Record linkage between registers provided malformation data. A matched case-control analysis was undertaken. Of the 632 cancer cases, 570 (90.2%) were linked to the VPDR. The congenital malformation prevalence in children with cancer was 9.6% compared with 2.5% in the controls [odds ratio (OR) 4.5, 95% CI 3.1-6.7]. A strong association was found with chromosomal defects (OR=16.7, 95% CI 6.1-45.3), in particular Down's syndrome (OR=27.1, 95% CI 6.0-122). Most other birth defect groups were also associated with increased cancer risk. The increased risk of leukaemia in children with Down's syndrome was confirmed, and children with central nervous system (CNS) defects were found to be at increased risk of CNS tumours. The report confirms that children with congenital malformations have increased risks of various malignancies. These findings may provide clues to the underlying aetiology of childhood cancer, as congenital malformations are felt to be a marker of exposures or processes which may increase cancer risk. The usefulness of record linkage between accurate population-based registers in the epidemiological study of disease has also been reinforced.
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ItemHave increases in solar ultraviolet exposure contributed to the rise in incidence of non-Hodgkin's lymphoma?(NATURE PUBLISHING GROUP, 1996-04)The incidence of non-Hodgkin's lymphoma (NHL) has increased substantially in many countries over recent decades. The aetiology of this cancer is poorly understood, and this rise is largely unexplained. The incidence of NHL is known to increase markedly following immune suppression. In the light of evidence that exposure to ultraviolet radiation (UVR) may cause systemic immune suppression, part of the recent increase in NHL incidence may reflect population-based increases in UVR exposure. That such exposure increases have occurred is inferred from the widespread increases in skin cancer incidence in fair-skinned populations, especially malignant melanoma (MM), over recent decades. Epidemiological evidence presented here in support of the proposed UVR-NHL relationship includes the following: in Caucasian populations there is a moderate positive correlation between ambient UVR level, by latitude, and NHL incidence; there is also a positive correlation between time trends in MM incidence and NHL; there is some evidence that migration across latitude gradients induces concordant shifts in risks of NHL and MM. Data from two historical cancer patient registers show that, in individuals, these two cancers concurred a little more often than expected. These findings support recent suggestions that UVR-induced impairment of immune functioning contributes to the aetiology of NHL.
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ItemCERVICAL CYTOLOGY REPORTED AS NEGATIVE AND RISK OF ADENOCARCINOMA OF THE CERVIX - NO STRONG EVIDENCE OF BENEFIT(NATURE PUBLISHING GROUP, 1995-04)The relationship between negative cervical cytology reports and risk of adenocarcinoma of the cervix was evaluated in a case-control study of 113 cases and 452 controls. All cases and controls had received at least two negative cytology reports. There was no significant difference between the cases and controls in the number of negative cytology reports or in history of cervical abnormality; while a test for trend in the time since last negative cytology report was significant (P < 0.001), the estimated benefit was very modest. Although the estimates of relative protection were higher in women aged less than 35 years than in women aged 35-69 years, this difference was not statistically significant. These results suggest that cervical screening as practised in the 1970s and 1980s was much less effective in preventing adenocarcinoma than squamous carcinoma of the cervix.
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ItemMortality from cutaneous melanoma: evidence for contrasting trends between populations(NATURE PUBLISHING GROUP, 2000-06)In recent years several reports have been published concerning trends in melanoma mortality in different countries, some of which have indicated that rates are beginning to fall. Many of these reports, however, have been based on small populations and have used different forms of statistical analysis. Our objective was to analyse systematically to what degree the epidemic of melanoma mortality had evolved similarly in different populations and whether there were any divergent trends that might increase our understanding. Instead of using all available data, we focused on countries with a minimum time series of 30 years and a minimum of 100 deaths annually in at least one sex from melanoma. We first inspected sex-specific age-standardized mortality rates and then performed age-period-cohort modelling. We found that the increase in mortality observed after 1950 was more pronounced in the age group 60-79. Statistical modelling showed a general increase in mortality rates in generations born after the turn of the century. Downturns in mortality, essentially in women and starting with generations born just before World War II, were found in Australia (where the earliest decreases were noted), the Nordic countries and the USA. Small decreases in rates in more recent generations were found in the UK and Canada. However, in France, Italy and Czechoslovakia, mortality rates were seen to be still increasing in recent cohorts. Our analysis suggests that populations are at different places on the melanoma mortality epidemic curve. The three trend patterns we observed are in agreement with time differences between populations with respect to the promotion of sun protection and the surveillance of pigmented skin lesions.
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ItemCytomegalovirus, Epstein-Barr virus and risk of breast cancer before age 40 years: a case-control study(NATURE PUBLISHING GROUP, 2004-06-01)We investigated whether there is an association between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) IgG levels and risk of breast cancer before age 40 years. CMV and EBV IgG levels were measured in stored plasma from 208 women with breast cancer and 169 controls who participated in the Australian Breast Cancer Family Study (ABCFS), a population-based case-control study. CMV and EBV IgG values were measured in units of optical density (OD). Cases and controls did not differ in seropositivity for CMV (59 and 57% respectively; P=0.8) or EBV (97 and 96% respectively; P=0.7). In seropositive women, mean IgG values were higher in cases than controls for CMV (1.20 vs 0.98 OD, P=0.005) but not for EBV (2.65 vs 2.57 OD, P=0.5). The adjusted odds ratios per OD unit were 1.46 (95% CI 1.06-2.03) for CMV IgG and 1.11 (0.93-1.33) for EBV IgG. The higher mean CMV IgG levels found in women with breast cancer could be the result of a more recent infection with CMV, and may mean that late exposure to CMV is a risk factor for breast cancer.
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ItemRisk factors for breast cancer in young women by oestrogen receptor and progesterone receptor status(NATURE PUBLISHING GROUP, 2003-11-03)We used data from 765 cases and 564 controls in the population-based Australian Breast Cancer Family Study to investigate whether, in women under the age of 40, the profile of risk factors differed between breast cancer subtypes defined by joint oestrogen and progesterone receptor status. As hypothesised, no significant differences were found.
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ItemNo Preview AvailableNo evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer(BMC, 2002)BACKGROUND: There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case-control study. METHODS: The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case-control analyses and genotype distributions were compared by logistic regression. RESULTS: The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59-1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85-1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. CONCLUSION: The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.
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ItemNo Preview AvailableThe intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia(BIOMED CENTRAL LTD, 2001)BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in breast cancer susceptibility. METHOD: We genotyped 71 familial breast cancer patients and 143 control individuals for the G13964C variant using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. RESULTS: Three (4.2%; 95% confidence interval [CI] 0-8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6-6.4%) control individuals without breast cancer or a family history of breast cancer, however, which is no different to the proportion found in familial cases (P = 0.9). CONCLUSION: The present study would have had 80% power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C polymorphism is not a 'high-risk' mutation for familial breast cancer.
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ItemThe AIB1 glutamine repeat polymorphism is not associated with risk of breast cancer before age 40 years in Australian women(BMC, 2005)INTRODUCTION: AIB1, located at 20q12, is a member of the steroid hormone coactivator family. It contains a glutamine repeat (CAG/CAA) polymorphism at its carboxyl-terminal region that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer through altered sensitivity to hormones. METHODS: We evaluated this repeat polymorphism in the context of early-onset disease by conducting a case-control study of 432 Australian women diagnosed with breast cancer before the age of 40 years and 393 population-based control individuals who were frequency matched for age. Genotyping was performed using a scanning laser fluorescence imager. RESULTS: There were no differences in genotype frequencies between cases and control individuals, or between cases categorized by family history or by BRCA1 and BRCA2 germline mutation status. There was no evidence that the presence of one or two alleles of 26 glutamine repeats or fewer was associated with breast cancer (odds ratio = 1.03, 95% confidence interval = 0.73-1.44), or that women with alleles greater than 29 repeats were at increased risk of breast cancer. Exclusion of women who carried a BRCA1 or BRCA2 mutation (24 cases) and non-Caucasian women (44 cases) did not alter the risk estimates or inferences. We present raw data, including that on mutation carriers, to allow pooling with other studies. CONCLUSION: There was no evidence that risk of breast cancer depends on AIB1 CAG/CAA polymorphism status, even if affected women carry a mutation in BRCA1 or BRCA2.
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ItemCYP17 genetic polymorphism, breast cancer, and breast cancer risk factors:: Australian Breast Cancer Family Study(BMC, 2005)INTRODUCTION: Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T-->C polymorphism. METHODS: Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses. RESULTS: We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A2/A2 genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A1/A1 (wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions. CONCLUSION: We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene-environment interactions.