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J L Hopper

Publications and source records attributed to J L Hopper.

At least 37 records · Page 2Linked to original sources
PubMed2003

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia).

OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

Adenocarcinoma↗
PubMed2003

Sexual factors and prostate cancer.

OBJECTIVE: To assess whether prostate cancer might be related to hormone levels and, by inference, to differences in sexual activity. PATIENTS, SUBJECTS AND METHODS: In a case-control study of men with prostate cancer aged < 70 years at diagnosis and age-matched control subjects, information was collected on two aspects of sexual activity; the number of sexual partners and the frequency of total ejaculations during the third to fifth decades of life. RESULTS: There was no association of prostate cancer with the number of sexual partners or with the maximum number of ejaculations in 24 h. There was a negative trend (P < 0.01) for the association between risk and number of ejaculations in the third decade, independent of those in the fourth or fifth. Men who averaged five or more ejaculations weekly in their 20s had an odds ratio (95% confidence interval) of 0.66 (0.49-0.87) compared with those who ejaculated less often. CONCLUSIONS: The null association with the number of sexual partners argues against infection as a cause of prostate cancer in this population. Ejaculatory frequency, especially in early adult life, is negatively associated with the risk of prostate cancer, and thus the molecular biological consequences of suppressed or diminished ejaculation are worthy of further research.

Adult↗
PubMed2003

Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors.

BACKGROUND: The epidemiology of androgenetic alopecia (AGA) is not fully understood. Although a strong genetic basis has long been identified, little is known of its non-genetic causes. OBJECTIVES: To estimate the prevalence of and to determine risk factors for AGA in men aged 40-69 years in Australia. METHODS: Men (n = 1390) were recruited at random from the electoral rolls to serve as controls in a population-based case-control study of prostate cancer. All were interviewed in person and direct observations of AGA were made. Men were grouped into the following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and vertex AGA). Epidemiological data collected from these men were used for an analysis of risk factors for each AGA category using unconditional logistic regression with AGA category as the response variable adjusting for age, education and country of birth. RESULTS: The prevalence of vertex and full AGA increased with age from 31% (age 40-55 years) to 53% (age 65-69 years). Conversely, the proportion of men with only frontal AGA was very similar across all age groups (31-33%). No associations were found between pubertal growth spurt or acne, reports of adult body size at time of interview, urinary symptom score, marital status, or current smoking status or duration of smoking and the risk of any form of AGA. The consumption of alcohol was associated with a significant increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA had fewer female sexual partners but average ejaculatory frequency did not differ between men in different AGA categories. Reported weight and lean body mass at reaching maturity at about 21 years of age were negatively associated with vertex balding (P for trend < 0.05) but not with frontal AGA or full AGA. CONCLUSIONS: Evidence for environmental influences on AGA remains very slight. Our study failed to confirm previously reported or hypothesized associations with smoking and benign prostatic hypertrophy. The associations that we found with alcohol consumption and with lean body mass at age 21 years would be worthy of further research if they were able to be replicated in other studies.

Adult↗
PubMed2003

Determinants of bone density in 30- to 65-year-old women: a co-twin study.

UNLABELLED: Reported effects of body composition and lifestyle on bone mineral density in pre-elderly adult women have been inconsistent. In a co-twin study, we measured bone mineral density, lean and fat mass, and lifestyle factors. Analyzing within pair differences, we found negative associations between bone mineral density and tobacco use (2.3-3.3% per 10 pack-years) and positive associations with sporting activity and lean and fat mass. INTRODUCTION: Reported effects of body composition and lifestyle of bone mineral density in pre-elderly adult women have been inconsistent. METHODS: In a co-twin study of 146 female twin pairs aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar spine, total hip, and forearm, total body bone mineral content, and lean and fat mass. Height and weight were measured. Menopausal status, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Within-pair differences in bone measures were regressed through the origin against within-pair differences in putative determinants. RESULTS: Lean mass and fat mass were associated with greater bone mass at all sites. A discordance of 10 pack-years smoking was related to a 2.3-3.3% (SE, 0.8-1.0) decrease in bone density at all sites except the forearm, with the effects more evident in postmenopausal women. In all women, a 0.8% (SE, 0.3) difference in hip bone mineral density was associated with each hour per week difference in sporting activity, with effects more evident in premenopausal women. Daily dietary calcium intake was related to total body bone mineral content and forearm bone mineral density (1.4 +/- 0.7% increase for every 1000 mg). Lifetime alcohol consumption and walking were not consistently related to bone mass. CONCLUSION: Several lifestyle and dietary factors, in particular tobacco use, were related to bone mineral density. Effect sizes varied by site. Characterization of determinants of bone mineral density in midlife and thereafter may lead to interventions that could minimize postmenopausal bone loss and reduce osteoporotic fracture risk.

Adult↗
PubMed2002

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Adult↗
PubMed2001

The intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia.

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.

Adult↗
PubMed2001

Segregation analyses of 1,476 population-based Australian families affected by prostate cancer.

Segregation analyses aim to detect genetic factors that have a major effect on an individual's risk of disease and to describe them in terms of mode of inheritance, age-specific cumulative risk (penetrance), and allele frequency. We conducted single- and two-locus segregation analyses of data from 1,476 men with prostate cancer diagnosed at age <70 years and ascertained through population registries in Melbourne, Sydney, and Perth, Australia, and from their brothers, fathers, and both maternal and paternal lineal uncles. Estimation and model selection were based on asymptotic likelihood theory and were performed through use of the software MENDEL. All two-locus models gave better fits than did single-locus models, even if lineal uncles were excluded or if we censored data (age and disease status) for relatives at 1992, when prostate-specific-antigen testing started to have a major impact on the incidence of prostate cancer in Australia. Among the genetic models that we considered, the best-fitting ones included a dominantly inherited increased risk that was greater, in multiplicative terms, at younger ages, as well as a recessively inherited or X-linked increased risk that was greater, in multiplicative terms, at older ages. The recessive and X-linked effects were strongly confounded, and it was not possible to fit them together. Penetrance to age 80 years was approximately 70% (95% confidence interval [CI] 57%-85%) for the dominant effect and virtually 100% for the recessive and X-linked effects. Approximately 1/30 (95% CI 1/80-1/12) men would carry the dominant risk, and 1/140 (95% CI 1/220-1/90) would carry the recessive risk or 1/200 (95% CI 1/380-1/100) would carry the X-linked risk. Within discussed limitations, these analyses confirm the genetic heterogeneity, of prostate cancer susceptibility, that is becoming evident from linkage analyses, and they may aid future efforts in gene discovery.

Age of Onset↗
PubMed2001

More breast cancer genes?

A new gene associated with a high risk of breast cancer, termed BRCAX, may exist on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative genomic hybridization in order to identify a region of interest, which was apparently confirmed and refined using linkage analysis on an independent sample. The present commentary discusses this work. It also asks why there should exist genetic variants associated with susceptibility to breast cancer other than mutations in BRCA1 and BRCA2, and what might be their modes of inheritance, allele frequencies and risks. Replication studies will be needed to clarify whether there really is a tumour suppressor gene other than BRCA2 on chromosome 13q.

BRCA1 Protein↗
PubMed2001

Genetic epidemiology of female breast cancer.

Population-based studies of the genetic epidemiology of female breast cancer have shown that only a small proportion of familial aspects of the disease can be explained by what is currently known about its causes. These include mutations in the genes BRCA1 and BRCA2, associated with a 10- to 20-fold increased risk of developing breast cancer. There may be genetic or environmental factors that modify cancer risks in mutation carriers, not necessarily in the same way as they do in non-carriers. The "typical BRCA1/2 family" consists of a "sporadic case", not a multiple-case family. There are likely to be other dominantly- and even recessively-inherited genetic risks, including those influencing intermediate markers like mammographic densities. Unravelling all the causes of familial aggregation will be a major step in understanding the causes of female breast cancer.

BRCA2 Protein↗
PubMed2001

Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8 to 26-year-old female twins.

Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged 8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and 78 unpaired twins), measured on average 2.4 times (range 2-6) with an average of 1.8 years between measurements (range 0.7-6.7 years). Areal bone mineral density (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral content (BMC), total body soft tissue composition (lean mass and fat mass) were measured by dual-energy X-ray absorptiometry, and height and menarchial status were also recorded. Median annual changes in height were negligible at 4 years post-menarche. During the 'linear growth' period up to 4 years post-menarche, ABMD at the lumbar spine, total hip and femoral neck increased with annual change in lean mass by 1.7 (S.E.0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per year, respectively (all p<0.001), independently of changes in fat mass or height. During the 'post-linear growth' period, ABMD at the total hip and femoral neck increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per kilogram per year (all p < 0.01), independent of change in lean mass. Annual changes in total body BMC were associated with annual changes in lean mass (1.9 (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth (all p < 0.001). We conclude that changes in bone mineral measures are strongly associated with changes in lean mass during linear growth, while post-linear growth, changes in fat mass are the predominant, although weaker, predictor. These findings suggest that the strong cross-sectional association between bone mineral measures and lean mass is established during growth and development, and that fat mass emerges as a more powerful determinant of bone change in healthy adult females.

Absorptiometry, Photon↗
PubMed2001

Power of regression and maximum likelihood methods to map QTL from sib-pair and DZ twin data.

A common study design to map quantitative trait loci (QTL) is to compare the phenotypes and marker genotypes of two or more siblings in a sample of unrelated sib groups, and to test for linkage between chromosome location and quantitative trait values. The simplest case is sib pairs only, in particular dizygotic twin pairs, and a simple and elegant regression method was proposed by Haseman & Elston in 1972 to test for linkage. Since then, several other methods have been proposed to test for linkage. In this study, we derived the statistical power of linear regression and maximum likelihood methods to map QTL from sib pair data analytically, and determined which methods are superior under which set of population parameters. In particular, we considered four regression-based and three maximum likelihood-based approaches, and derived asymptotic approximations of the mean test statistic and statistical power for each method. It was found, both analytically and by computer simulation, that the revisited or new Haseman-Elston method (based upon the mean-corrected crossproduct of the observations on sib-pairs) is less powerful than a full maximum likelihood approach and is also inferior to the Haseman-Elston method under a realistic range of values for the population parameters. We found that a simple regression method, based upon both the squared difference and the mean-corrected squared sum of the observations on sib-pairs, is as powerful as a full maximum likelihood approach. Our derivations of statistical power for regression and maximum likelihood methods provide a simple way to compare alternative methods and obviate the need to perform elaborate computer simulations. DZ twin pairs are likely to be more powerful for linkage analysis than ordinary siblings because they may share more common environmental effects, thereby increasing the proportion of within-family variance that is explained by a QTL.

Chromosome Mapping↗
PubMed2001

Smoking and prostate cancer: findings from an Australian case-control study.

BACKGROUND: To examine the risk of smoking on histopathologically-confirmed moderate- and high-grade prostate cancer. MATERIALS AND METHODS: A population-based case-control study was conducted in Melbourne, Sydney and Perth between 1994 and 1998 in men aged below 70 years. Cases were recruited from cancer registries and controls were selected from electoral registers. 1498 cases and 1434 controls were interviewed and a detailed smoking history obtained. Data were analyzed by unconditional logistic regression, adjusting for age, study center, year of recruitment, family history and country of birth. RESULTS: The odds ratios (OR) were 1.02 (0.85-1.22) for former smoking and 0.82 (0.65-1.05) for current smoking. The respective ORs were 0.95 (0.78-1.15) and 0.76 (0.59-0.99) for moderate grade tumors, and 1.28 (0.96-1.70) and 1.00 (0.67-1.47) for high-grade tumors (P = 0.2 for test that ORs of the two grades were identical). There was no evidence of a dose-response effect for duration of smoking, amount smoked daily, pack-years of smoking and years since quitting and most ORs for these variables were close to unity. CONCLUSIONS: Smoking was not associated with the incidence of prostate cancer. The widths and upper limits of the confidence intervals for the effects of current and former smoking were consistent with weak effects at most.

Adult↗
PubMed2001

Prevalence of self-reported arm morbidity following treatment for breast cancer in the Australian Breast Cancer Family Study.

Population-based women (n=1049) with breast cancer diagnosed mainly between 1996 and 1998, when aged 20-59 years, were mailed a questionnaire seeking information about self-reported shoulder stiffness and swelling, numbness and pain/ache in the arm following treatment (excluding 6 months from diagnosis). Of the 809 who completed the survey, approximately seven in eight experienced at least one symptom, one in six reported all four symptoms, and one in three considered that their arm morbidity interfered substantially with activities of daily living. Arm swelling occurred at some time in 39% of women, was present in 20% 1 year, and in 29% 4 years, after diagnosis. The prevalence of arm swelling was higher in women with axillary node dissection (OR=2.4; 95% Cl 1.0-5.6), and was increased in a women with a higher body mass index (P=0.02) and less education (P=0.01), but was not related to age, number of nodes excised or self-reports of radiation or type of surgery.

Journal Article↗
PubMed2001

Distribution of family history of a disease as a function of mode of inheritance, genetic relative hazard, allele frequency and disease status of the proband, with application to female breast cancer.

BACKGROUND: This paper aims to determine the family history distribution of a particular disease as a result of its specific genetic aetiology, defined by the mode of inheritance (dominant or recessive), allele frequency, and increased risk in carriers of the genetic risk (genetic relative hazard). Here, 'family history' is the number of affected first-degree relatives of a defined index person (termed the proband), who may be either affected or unaffected with the disease in question. METHODS: We consider model parameters relevant for female breast cancer in Australia. Breast cancer affects one sex only, although the extension of the model to both sexes is straightforward. RESULTS: Contour plots of the relationships between family history distribution and genetic parameters, for both dominant and recessive inheritance, are displayed for the proband being either affected or unaffected. CONCLUSIONS: Under dominant inheritance and an allele frequency of 0.005 (as may be appropriate for mutations in the genes BRCA1 and BRCA2), the proportion of affected probands diagnosed with breast cancer before age 50 years and who have no family history is stable as the genetic relative hazard increases from 5 to 20, decreasing from 89% to 85%. The probability that a proband has a family history is higher when the proband is affected compared with when she is not. For allele frequency 0.005 and relative hazard 10, the ratio of the probability of i (i = 1, 2, 3 or more) affected relatives for an affected proband compared with an unaffected proband is 1.2, 2 and 4.5 respectively, under dominant inheritance. Under recessive inheritance with allele frequency 0.35 and relative hazard 3 (as may be the case for a common polymorphism in the CYP17 gene), the corresponding ratios are 1.1, 1.3 and 1.5, respectively.

Adult↗
PubMed2001

Association of birth weight and current body size to blood pressure in female twins.

It has been proposed that low birth weight is associated with high levels of blood pressure in later life. The aim of this study was to assess the relationship of blood pressure to birth weight and current body size during growth and adulthood. A total of 711 female multiple births, with one group of 244 in their growth phase mean age 12.0 (2.3)(SD) years and the other of 467 adults (mean age 35.2 (12.6) years), had height, weight and both systolic (SBP) and diastolic (DBP) blood pressures measured, and self-reported their birth weight. Regression analyses were performed to assess the cross-sectional and within-pair associations of blood pressure to birth weight, with and without adjustments for current body size. Within-pair analysis was based on 296 twin pairs. Cross-sectionally, a reduction in birth weight of 1 kg was associated with 2 to 3 mm Hg higher age-adjusted SBP, which was of marginal significance and explained about 2% of the population variance. Adjustment for body mass index did not significantly change this association. Within-pair analyses found no association between birth weight and SBP or DBP,even after adjusting for current body size. After age, current body size was the strongest predictor of systolic BP. The weak association of blood pressure to birth weight cross-sectionally is of interest, but any within-pair effect of birth weight on blood pressure must be minimal compared with the effect of current body size.

Birth Weight↗
PubMed2001

Analytical and graphical methods to model the association between family history and disease from a case-control study.

Subjects within a family have a high probability of sharing environmental factors as well as genes. Without any previous hypothesis, familial aggregation cannot be attributed to genetic or environmental factors. In epidemiology a common measure of familial aggregation is the odds ratio (OR) evaluated from case-control studies which gives a measure of the increased risk associated with particular aspects of the family's history of disease. An analytical method is presented to model the OR of case-control studies in the presence of risk factors, genetic or environmental, that are correlated between relatives. A graphical approach that can be used to link the parameters of the model with the values of the OR is also described. The method is illustrated using the example of familial aggregation in colorectal cancer.

Case-Control Studies↗
PubMed2001

The steroid 5alpha-reductase type II TA repeat polymorphism is not associated with risk of breast or ovarian cancer in Australian women.

The enzyme 5alpha-reductase type II (SRD5A2) converts testosterone to its more active form 5alpha-dihydroxytestosterone. The 3' untranslated region of the gene contains a (TA)(n) length polymorphism. The (TA)(9) allele has been reported to be associated with higher serum prostate-specific antigen levels in breast tumors and lower risk of relapse in breast cancer patients and more recently has also been reported to be linked to the codon 89 valine variant, which is itself associated with higher serum prostate-specific antigen levels in breast tumors and a more favorable breast cancer prognosis. We investigated whether the SRD5A2 (TA)(n) polymorphism was associated with risk of breast or ovarian cancer in Australian women by studying 946 breast cancer cases and 509 age-matched controls, and 544 ovarian cancer cases and 298 controls of similar age distribution. The (TA)(9) allele frequency was similar in breast cancer cases (0.110), breast cancer controls (0.125), ovarian cancer cases (0.106), and ovarian cancer controls (0.117). There was no difference in genotype distribution between breast cancer cases and controls (P = 0.5), ovarian cancer cases and controls (P = 0.7), or between the two control groups (P = 0.9). Genotypes containing at least one (TA)(9) allele were not significantly associated with risk of breast cancer overall (odds ratio, 0.86; 95% confidence interval, 0.67-1.12; P = 0.3) or in women stratified by age, menopausal status, or family history. Similarly, the (TA)(9) allele was not associated with risk of ovarian cancer (odds ratio, 0.87; 95% confidence interval, 0.61-1.23; P = 0.4) or with ovarian tumor behavior (invasive or low malignant potential), histology, stage, or grade. Given that this study had sufficient power to detect altered risks in the order of 1.4- to 1.7-fold, our results suggest that the SRD5A2 (TA)(9) allele is unlikely to be associated with moderate alterations in breast or ovarian cancer risk.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗