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Background: Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.Methods: We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.Results: For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57-26.26) and 12.52 (5.21-30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1-49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64-74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91-5.93), 5.25 (2.50-11.01), 7.73 (4.74-12.62), 5.19 (2.33-11.54) and 4.35 (1.81-10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers.Conclusion: First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations. [ABSTRACT FROM AUTHOR]

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.British Journal of Cancer (2004) 90, 2149-2152. doi:10.1038/sj.bjc.6601822 www.bjcancer.com Published online 20 April 2004 [ABSTRACT FROM AUTHOR]

Background: The cytochrome P450c17alpha enzyme functions in the steroid biosynthesis pathway, and altered endogenous steroid hormone levels have been reported to be associated with a T to C polymorphism in the 5' promoter region of the CYP17 gene. Because steroid hormone exposure is known to influence breast cancer risk, we conducted a population-based, case-control-family study to assess the relationship between the CYP17 promoter polymorphism and early-onset breast cancer.Methods: Case subjects under 40 years of age at diagnosis of a first primary breast cancer, population-sampled control subjects, and the relatives of both case and control subjects were interviewed to record family history of breast cancer and other risk factors. CYP17 genotype was determined in 369 case subjects, 284 control subjects, and 91 relatives of case subjects. Genotype distributions were compared by logistic regression, and cumulative risk was estimated by a modified segregation analysis. All statistical tests were two-tailed.Results: Compared with the TT genotype (i.e., individuals homozygous for the T allele), the TC genotype was not associated with increased breast cancer risk (P: =.7). Compared with the TT and TC genotypes combined, the CC genotype was associated with a relative risk of 1. 81 (95% confidence interval [CI] = 1.15-2.86; P: =.01) before adjustment for measured risk factors and 1.63 (95% CI = 1.00-2.64; P: =.05) after adjustment. There was an excess of CC genotypes in case subjects who had at least one affected first- or second-degree relative, compared with control subjects unstratified by family history of breast cancer (23% versus 11%; P: =.006), and these case subjects had a threefold to fourfold higher risk than women of other groups defined by genotype and family history of breast cancer. Analysis of breast cancer in first- and second-degree relatives of case subjects with the CC genotype, excluding two known carriers of a deleterious mutation in BRCA1 or BRCA2, gave a relative hazard in women with the CC genotype of 3.48 (95% CI = 1.13-10.74; P: =.04), which is equivalent to a cumulative risk of 16% to age 70 years.Conclusions: The CC genotype may modify the effect of other familial risk factors for early-onset breast cancer. [ABSTRACT FROM AUTHOR]

Routinely collected data for New South Wales were used to analyse cancer mortality in migrants born in East or Southeast Asia according to duration of residence in Australia. A case-control approach compared deaths from cancer at particular sites with deaths from all other cancers, adjusting for age, sex and calendar period. Compared with the Australian-born, these Asian migrants had a 30-fold higher risk of dying from nasopharyngeal cancer in the first 2 decades of residence, falling to ninefold after 30 years, and for deaths from liver cancer, a 12-fold risk in the first 2 decades, falling to threefold after 30 years. The initial lower risk from colorectal, breast or prostate cancers later converged towards the Australian-born level, the change being apparent in the third decade after migration. The relative risk of dying from lung cancer among these Asian migrants was above unity for each category of duration of stay for women, but at or below unity for men, with no trend in risk over time. An environmental or lifestyle influence for nasopharyngeal and liver cancers is suggested as well as for cancers of colon/rectum, breast and prostate. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is more common in Maori than in non-Maori women under the age of 40 years and is equally common in older women, despite Maori being generally of lower socioeconomic status and having had a higher fertility rate than non-Maori.Methods: Data from a nationwide population-based case-control study of breast cancer in New Zealand women aged 25-54 years were used to compare the age-adjusted distribution of reproductive and other risk factors for breast cancer in self-identified Maori and non-Maori women from the control group. Separate analyses also were carried out for women aged 25-39 years and for those aged 40-54 years. The risk of breast cancer according to the proportion of Maori ancestry was estimated using multiple logistic regression simultaneously adjusting for several risk factors.Results: Significant differences were found between self-identified Maori and non-Maori women in the age-adjusted frequencies for education level, socioeconomic status, age at first full-term pregnancy, parity, and duration of breastfeeding; the profile in all instances suggesting a lower risk of breast cancer for Maori than for non-Maori. There were no significant differences with respect to age at menarche, surgery for benign breast disease or a family history of breast cancer. Significantly more Maori than non-Maori were in the highest quartile of recent body mass index. Women self-identified as Maori has an approximately twofold higher risk of breast cancer than non-Maori women.Conclusions: Maori have high rates of breast cancer despite having a more favourable profile than non-Maori for most identified risk factors. [ABSTRACT FROM AUTHOR]

A series of co-ordinated population-based case-control studies of childhood brain tumours (CBT) was undertaken under the auspices of the Surveillance of Environmental Aspects Related to Cancer in Humans (SEARCH) programme of the International Agency for Research on Cancer (IARC) to evaluate, inter alia, the risk in relation to characteristics of the index pregnancy and birth, and maternal reproductive history. Subjects comprised 1218 cases aged 0-19 years and 2223 controls. Risk estimates were calculated by unconditional logistic regression, adjusted for age, sex, centre and mother's years of schooling, for all types of CBT combined as well as for four groups defined by histopathology (astrologlial tumours, primitive neuroectodermal tumours of the brain, 'other glial' tumours and 'other histological types') and for five age groups (0-1, 0-4, 5-9, 10-14, 15-19 years). Use of anaesthetic 'gas' was associated with an increased risk of CBT (OR = 1.5, 95% CI [1.1, 2.0]), apparent in children aged 0-4 years (OR = 2.4, 95% CI [1.4, 4.1]) and for astroglial tumours (OR = 1.6, 95% CI [1.1, 2.2]) with non-significantly increased relative risks for each of the other histological groups. However, not all centre-specific relative risks were elevated. No other aspect of the index pregnancy, delivery and early neonatal period or of the mother's previous reproductive history was associated with risk for CBT. [ABSTRACT FROM AUTHOR]

Background: A recent meta-analysis of 23 studies supported the empirically derived hypothesis that women who lack one of the four common minisatellite alleles at the HRAS1 locus are at increased risk of breast cancer. These studies relied on visual sizing of alleles on electrophoretic gels and may have underreported rare alleles. We determined whether this hypothesis applied to early-onset breast cancer by using a new method to size minisatellite alleles.Methods: We conducted a population-based, case-control-family study of 249 Australian women under 40 years old at diagnosis of a first primary breast cancer and 234 randomly selected women, frequency matched for age. We sized HRAS1 minisatellite alleles with an Applied Biosystems model 373 automated DNA sequencer and GENESCAN(TM) software. All P values are two-sided.Results: We found no association of rare alleles with breast cancer, before or after adjustment for risk factors and irrespective of how their effects were modeled (crude odds ratio = 1.04; 95% confidence interval [CI] = 0.071-1.53; P =.8). The rare allele frequency was 0. 173 (95% CI = 0.149-0.197), three times the pooled estimate of 0.058 (95% CI = 0.050-0.066) from previous studies (P<.001), and was similar for case subjects, 0.177 (95% CI = 0.143-0.221), and control subjects, 0.169 (95% CI = 0.135-0.203) (P =.7).Conclusion: There was no support for an association between rare HRAS1 alleles and the risk of early-onset breast cancer, despite 80% power to detect effects of the magnitude of those associations (1.7-fold) previously suggested.Implications: The question of whether cancer risk is associated with rare minisatellite HRAS1 alleles needs to be revisited with the use of new methods that have a greater ability to distinguish rare alleles from similarly sized common alleles. [ABSTRACT FROM AUTHOR]

Objectives: We have assessed the effect on the rates of cancers of the kidney and bladder of measures undertaken by the government in 1979-1983 to limit smoking and analgesic abuse in New South Wales (NSW). Sale of phenacetin-containing analgesics, previously available without restriction and regularly taken by 11-13% of women and 4-9% of men in NSW, was prohibited from 1979. The prevalence of current smokers among adult Australian men had fallen from 72% in 1945 to 43% in 1980 and to 28% in 1992. In women the corresponding figures were 26%, 31% and 24%.Methods: Incidence and mortality data from the New South Wales Central Cancer Registry for the period 1972 to 1995 were analyzed, by sex and age, for trends over time. Relative survival was calculated for cases diagnosed in the period 1980-94 and followed until the end of 1996.Results: Significant trends evident from these data were: throughout the period of review a rising incidence of, and to a lesser extent mortality from, renal parenchymal cancer for which relative survival has steadily improved; falling mortality from bladder cancer throughout the period of review, but more rapid after 1985; a reversal of the earlier increasing incidence of, and mortality from, cancer of the renal pelvis; and relative survival for bladder and renal pelvic cancers which was worse in women than men. Changes in registration practice in 1985 and 1993 introduced artifacts into the trends in incidence of bladder cancer.Conclusions: Improvements in the trends of incidence and mortality of cancers of the renal pelvis and bladder in the mid-1980s are interpreted, in the light of registration and clinical practice, to indicate a beneficial effect of regulations which virtually abolished analgesic abuse and, less certainly, a contribution from measures restricting smoking, in New South Wales. However, renal parenchymal cancer continues to increase, although there has been some apparent benefit of earlier detection. [ABSTRACT FROM AUTHOR]

Objectives: Because the factors that influence risk of acral melanomas on the soles and palms in White populations are unknown, we investigated these in a multi-center case-control study.Methods: Cases of melanoma of the feet and hands diagnosed from 1987-93 in persons aged over 18 years were ascertained in eastern Australia and western Scotland. There were 275 cases of melanoma on the soles and palms matched to 496 controls (selected from the electoral roll) in Australia, and 36 cases matched to 72 controls (nominated by general practitioners) in Scotland.Results: Acral melanoma was strongly associated with high total body nevus counts (adjusted relative risk [RR] = 6.3, 95% confidence interval [CI] = 2.5-15.6), and with nevi on the soles (RR = 7.5, CI = 3.0-18.6). There were also significant positive associations with a penetrative injury of the feet or hands (RR = 5.0, CI = 3.0-8.6) and with heavy exposure to agricultural chemicals (RR = 3.6, CI = 1.5-8.3). Sun-sensitive complexions, cumulative sun exposure and a past history of nonmelanoma skin cancer were also associated with increased risk of acral melanoma. Current cigarette smoking was inversely related to acral melanoma (RR = 0.6, CI = 0.4-0.9).Conclusions: Melanomas of the soles and palms resemble other cutaneous melanomas in their association with sun exposure, but are distinguished from them by their strong positive associations with nevi on the soles, previous penetrative injury, and exposure to agricultural chemicals, and by their inverse association with smoking. [ABSTRACT FROM AUTHOR]

Data from the New South Wales (NSW) Central Cancer Registry for 1972-91 were examined to determine the risk of a second primary cancer following an initial invasive cancer of the cervix uteri (ICD-9 180), corpus uteri (ICD-9 182), ovary (ICD-9 183) or 'other female genital organs' (ICD-9 184). Expected numbers of cancers were obtained by assuming that women with a cancer of the female genital tract experienced the same cancer incidence as the female population of NSW as a whole. The relative risk (RR) of a second primary cancer was the ratio of observed to expected numbers of second cancers, excluding those of the female genital tract. Following cervical cancer, significantly increased risks were found for cancer of the larynx (RR= 7.43), lung (RR = 3.64), bladder (RR = 3.36) and for all tobacco-related sites (excluding cervix and bladder) grouped together (RR = 2.54). A nonsignificant excess of anal cancer (RR = 4.23) was also seen. After an initial cancer of the corpus uteri significantly increased risks were found for colorectal (RR = 1.35), breast (RR = 1.36) and bladder cancers (RR = 1.95). The excess of colorectal cancer bordered on significance (RR = 1.43) but there was no increased risk of breast cancer (RR = 1.02) after ovarian cancer. The data illustrate the need for surveillance of women with cervical cancer for further tobacco-related cancers, and the risk of treatment-initiated neoplasms. [ABSTRACT FROM AUTHOR]

Background: The estrogen receptor (ER) protein is believed to play a role in the development and progression of breast cancer. In a previously published U.S. clinic-based study, a polymorphism in the ER gene (codon 325, CCC --> CCG) was found to be more common in 34 case subjects with a family history of breast cancer than in 154 case subjects without such a history (mean allele frequencies +/- standard error = 0.28+/-0.05 versus 0.11+/-0.02; P<.001). To determine whether this polymorphism is a risk factor for early-onset breast cancer, we conducted a population-based, case-control-family study in Australia.Methods: Case subjects under the age of 40 years with a first primary breast cancer and control subjects, frequency-matched to the case subjects on the basis of age, and their relatives were interviewed to assess the family history of breast cancer. Polymorphism status of the ER gene was determined for 388 case subjects and 294 control subjects. All statistical tests were two-tailed.Results: There was no association between ER gene polymorphism status and breast cancer, before or after adjustment for risk factors. There was no difference in allele frequencies between case subjects and control subjects (0.232+/-0.015 versus 0.209+/-0.017; P = .4) or between women with and without a family history of breast cancer (P = .3), irrespective of case-control status. The findings were not altered when different definitions of family history of breast cancer were used and when allele frequencies were adjusted for residence and country of birth.Conclusion: We found no evidence that the ER codon 325 polymorphism is associated with breast cancer before the age of 40 years or with a family history of breast cancer, despite ample power to detect effects half the magnitude of those previously reported. [ABSTRACT FROM AUTHOR]

Objectives: A case-control-family study of breast cancer in women under the age of 40 was carried out in Melbourne and Sydney, Australia, from 1992 to 1995 to determine the risk factors for these women. Subjects included 467 incident cases identified by state cancer registries and 408 population-based controls.Methods: All participants completed a structured risk-factor questionnaire and family pedigree during an in-person interview. Where possible, cancers in first- and second-degree relatives were verified.Results: Multiple logistic regression analysis showed that the strongest risk factor for breast cancer was a family history of the disease -- having at least one affected first-degree relative trebled the risk (relative risk [RR] = 3.3, 95 percent confidence interval [CI] = 1.9-5.8). Risk increased with height by three percent (standard error [SE] of one percent) per cm, and after adjusting for height, there was evidence for a decreased risk in women weighing 73 kg or more. There was an increased risk of breast cancer after the first full-term birth (RR = 1.8, CI = 1.0-3.5) but this risk fell by 30 percent (SE = 11 percent) with each subsequent livebirth.Conclusions: The effects of other reproductive factors and oral contraceptive use, although not nominally significant, were in accord with published findings from similar studies in young women. This study of Australian women has indicated that some risk factors for breast cancer in women under age 40 differ from those reported for older women either in direction (e.g., weight) or relative importance (e.g., family history). [ABSTRACT FROM AUTHOR]

Age-specific and cumulative incidence rates were calculated for entry into Australian end-stage renal failure programmes from 1972 to 1991, as a result of all causes, or from analgesic nephropathy, glomerulonephritis, hypertension and vascular disease, or diabetes. Three different trends were demonstrated. A rising recorded incidence of renal failure occurred throughout the period of observation in those aged 0–4 years (all causes) and in those aged 55 years and over (all categories, least in analgesic nephropathy) principally attributable to a falling fraction of patients not accepted for treatment. Falling incidence rates indicating a real reduction in the burden of disease were seen for analgesic nephropathy (at least up to the age of 64 years) and hypertension and vascular disease (only up to the age of 54 years). In young adults the unchanging incidence of renal failure due to all causes, glomerulonephritis and diabetes probably reflect nearly complete acceptance rates into end-stage renal failure programmes, and therefore approximate the true burden of disease. In end-stage renal failure, age- specific or age-standardized cumulative rates are required to distinguish rising or falling incidence of disease from trends due to changing medical practice. [ABSTRACT FROM PUBLISHER]

Incidence and mortality rates for oral and pharyngeal cancers have been reported to be increasing in Europe and the United States, with particularly large increases in mortality in central and eastern Europe. Such increases have been noted to be birth cohort-based, primarily affecting young and middle-aged men. In this report oral and pharyngeal cancer incidence data from New South Wales, Australia has been analysed for the period 1972-90. Although an increase in the incidence of oral and pharyngeal cancer occurred during the mid-1970s and early 1980s, it did not continue. This pattern is consistent with Australian trends in per capita consumption of tobacco, alcohol, fruit and vegetables. Individual regions within metropolitan Sydney showed substantial geographical variation with age-specific rates of oral and pharyngeal cancers (combined) in middle-aged men being at least three times higher in the city of Sydney than in New South Wales as a whole. Given the preventable nature of the disease, such high rates need not occur. [ABSTRACT FROM AUTHOR]

The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region ofBRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation inBRCA1 was estimated to be 3.8% (95% Cl 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence. [ABSTRACT FROM AUTHOR]

Pregnancy can cause life threatening complications in women with mitral stenosis, and there is a substantial risk of fetal death if valvotomy under cardiopulmonary bypass is required. A patient is described in whom pulmonary oedema developed after delivery of her first child by caesarean section 13 months previously. Subsequent cardiac catheterisation showed severe mitral stenosis (valve area 0.96 cm2, valve gradient 12 mm Hg, pulmonary artery pressure 30/16 mm Hg). Before valvotomy could be performed the patient again became pregnant and presented in pulmonary oedema at twenty two weeks' gestation. Medical treatment was unsuccessful and she underwent percutaneous transluminal balloon dilatation of the mitral valve. This increased the valve area to 1.78 cm2 and reduced the transmitral gradient to 6 mm Hg. The procedure was uncomplicated, and she remained symptom free on no medication. She delivered vaginally at 37 weeks' gestation. Percutaneous transluminal balloon dilatation of the mitral valve is a safe and effective alternative to mitral valvotomy in pregnancy. [ABSTRACT FROM PUBLISHER]

Background: Previous studies have suggested that the frequency of cancer is higher in patients with end-stage renal disease (ESRD) than in the general population, but have not established whether this increase is confined to certain cancers or to certain categories of ESRD patients. The aim of this study was to examine the risk of cancer in a large cohort of patients treated by dialysis but not transplantation.Methods: We assembled a cohort of 831,804 patients who received dialysis during the period 1980-94 for ESRD in the USA, Europe, Australia, or New Zealand. We compared the observed frequency of cancer among these patients during 2,045,035 person-years of follow-up with the frequency of cancer in the respective background populations.Findings: During average follow-up of 2.5 years, 25,044 (3%) of 831,804 patients developed cancer compared with an expected number of 21,185 (standardised incidence ratio 1.18 [95% CI 1.17-1.20]). We observed a higher risk of cancer in patients younger than 35 years (3.68 [3.39-3.99]), and the risk gradually decreased with increasing age. High risks were observed for cancer of the kidney (3.60 [3.45-3.76]), bladder (1.50 [1.42-1.57]), and thyroid and other endocrine organs (2.28 [2.03-2.54]). Excess cancers appeared in several organs for which viruses have been suspected as causative agents, whereas cancers of the lung, colorectum, prostate, breast, and stomach were not consistently increased.Interpretation: The overall risk of cancer is increased in patients with ESRD, and the distribution of tumour types resembles the pattern seen after transplantation (although we have no data to make the comparison with skin cancer). The excess risk can largely be ascribed to effects of underlying renal or urinary-tract disease, or of loss of renal function, on the kidney and bladder, and to increased susceptibility to viral carcinogenesis. The relative risk, which is especially high in younger patients, gradually diminishes with age. [ABSTRACT FROM AUTHOR]