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A population-based case-control study of incident primary malignant brain tumours diagnosed during 1985-1989 in children aged 0 to 14 years was carried out in the coastal conurbation of New South Wales comprising Sydney, Wollongong and Newcastle in the period 1988 to 1990. Personal interviews were conducted using a structured questionnaire with mothers of 82 cases and 164 control children individually matched to the cases by sex and age. Among the hypotheses examined were those related to: N-nitroso compounds (sources included diet, dummies, medications, tobacco smoke); factors associated with the birth of the child; trauma to the head; and irradiation (X-rays and electromagnetic radiation through electric blankets or water beds). Reported ever-use of a dummy increased the risk of childhood brain tumours (OR = 2.9, 95% CI 1.6 to 5.4), although there did not appear to be any consistent indication of rising risk with reported increased levels of use. Compared with children who had never used a dummy, categories of use during the first year of life of a maximum of "no more than 1 hour per day or night", "several hours per day or night", and "most of the day or night" had statistically significant odds ratios of 2.6, 3.4, and 2.7 respectively. Consumption of fruit by the child before the age of one appeared to be protective. No association was found between childhood brain tumours and birth weight, being the first-born child, or factors linked with the child's birth; head injuries; exposure to X-rays; contact with horses, or living on a farm; pesticide treatment of the house during the child's lifetime; or exposure to burning incense.

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.

A C to T transition within the 3' untranslated region of the prohibitin gene alters mRNA function, and an association between the T allele and an increased risk of breast cancer has been reported in North American women, specifically in those aged under 50 years with a first-degree family history of breast cancer. We did a population-based case-control study to assess whether this association existed in Australian women. We did not note such an association in our sample of 1446 patients and 786 controls (odds ratio 0.96, 95% CI 0.80-1.16; p=0.7), or in subgroups defined by age or family history, or both. Hence, our results do not lend support to the hypothesis that this polymorphism contributes to risk of breast cancer.

A population-based case-control study of kidney cancer was carried out in New South Wales using data from structured interviews with 489 cases of renal-cell cancer and 147 cases of renal pelvic cancer diagnosed in 1989 and 1990, together with 523 controls from the electoral rolls. This study showed that the risk of renal pelvic cancer was increased by phenacetin/aspirin compound analgesics (RR = 12.2; 95% CI 6.8-22.2) to a far greater extent than by paracetamol (RR = 1.3; 95% CI 0.7-2.4; not significant). There was a doubling of risk (RR = 2.0; 95% CI 0.9-4.4) in the highest tertile of paracetamol taken in any form compared with values for non-users of any type of analgesic. By contrast, the risk of renal-cell cancer appeared to be increased to a similar degree by phenacetin/aspirin compound analgesics (RR = 1.4; 95% CI 0.9-2.3) and paracetamol taken in any form (RR = 1.5; 95% CI 1.0-2.3). When both drugs were treated as alternative forms of the same risk factor, the risk was increased by 1.7 (95% CI 1.2-2.4). On this evidence, we postulate that phenacetin/aspirin compounds are weakly carcinogenic in the renal parenchyma through the metabolic conversion of phenacetin to paracetamol, and potently carcinogenic in the renal pelvis by different or additional pathways involving renal papillary necrosis. In addition, there is an indication of a weak link between paracetamol and renal pelvic cancer.

Objective To compare cancer incidence in kidney transplant recipients during periods of transplant function (and immunosuppression) and after transplant failure (when immunosuppression is ceased or reduced). Design, setting, and participants Nationwide, population based retrospective cohort study of 8173 Australian kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry who first received a transplant during 1982-2003. Incident cancers were ascertained using linkage with national cancer registry records. Main outcome measures Cancer-specific standardised incidence ratios for periods of transplant function and for dialysis after transplant failure. Incidence was compared between periods using multivariate incidence rate ratios adjusted for current age, sex, and duration of transplantation. Results All cases of Kaposi’s sarcoma occurred during transplant function. Standardised incidence ratios were significantly elevated during transplant function, but not during dialysis after transplant failure, for non-Hodgkin’s lymphoma, lip cancer, and melanoma. For each of these cancers, incidence was significantly lower during dialysis after transplant failure in multivariate analysis (incidence rate ratios 0.20 (95% CI 0.06 to 0.65) for non-Hodgkin’s lymphoma, 0.04 (0.01 to 0.31) for lip cancer, and 0.16 (0.04 to 0.64) for melanoma). In contrast, standardised incidence ratios during dialysis after transplant failure remained significantly elevated for leukaemia and lung cancer, and cancers related to end stage kidney disease (kidney, urinary tract, and thyroid cancers), with thyroid cancer incidence significantly higher during dialysis after transplant failure (incidence rate ratio 6.77 (2.64 to 17.39)). There was no significant difference in incidence by transplant function for other cancers. Conclusions The effect of immunosuppression on cancer risk is rapidly reversible for some, but not all, cancer types. Risk reversal was mainly observed for cancers with a confirmed infectious cause. Risk of other cancers, especially those related to end stage kidney disease, remained significantly increased after reduction of immunosuppression.

In a population-based case-control study of kidney cancer in New South Wales, Australia, data from structured interviews with 489 cases of renal cell cancer (RCC) and 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls, confirmed the link between obesity and RCC. In addition, regular consumption of 'diet' pills independently increased the risk for this cancer. A diagnosis of hypertension at least two years before interview raised the risk for RCC, and regular use of beta-blockers, a class of antihypertensive drug, independently increased the risk for RCC and CaRP (risk ratio = 1.5-1.8). No independent effect was found for use of diuretics. Additional information provided by this study includes increased risks associated with kidney injury (RCC, CaRP)--possibly attributed to recall bias--and kidney infection (CaRP), as well as a nonsignificantly raised risk linked with kidney stones (RCC, CaRP) and a significantly reduced risk for RCC in persons giving a history of lower urinary tract infection. No significant association of RCC was found with hormonal factors (age at menarche or menopause; child-bearing; regular use of oral contraceptives or estrogens; hysterectomy or oophorectomy).

Nat. Genet. 39, 352–358 (2007); published online 11 February 2007; corrected 10 April 2007 In the version of this article initially published, there was an error that affected the calculations of the odds ratios, confidence intervals, between-study heterogeneity, trend test and test for association for SNP ICAM5 V301I in Table 1 (ICAM5 V301I); genotype counts in Supplementary Table 2 (ICAM5; ICR_FBCS and Kuopio studies) and minor allele frequencies, trend test and odds ratios for heterozygotes and rare homozygotes in Supplementary Table 3 (ICAM5; ICR_FBCS and Kuopio studies).

ContextImmune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer and a few virus-associated cancers. Although it is generally accepted that other cancers do not occur at increased rates, there have been few long-term population-based cohort studies performed.ObjectiveTo compare the incidence of cancer in patients receiving immune suppression after kidney transplantation with incidence in the same population in 2 periods before receipt of immune suppression: during dialysis and during end-stage kidney disease before renal replacement therapy (RRT).Design, Setting, and ParticipantsA population-based cohort study of 28 855 patients with end-stage kidney disease who received RRT, with 273 407 person-years of follow-up. Incident cancers (1982-2003) were ascertained by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House.Main Outcome MeasureStandardized incidence ratios (SIRs) of cancer, using age-specific, sex-specific, calendar year–specific, and state/territory–specific population cancer incidence rates.ResultsThe overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased after transplantation (n = 1236; SIR, 3.27; 95% confidence interval [CI], 3.09-3.46). In contrast, cancer incidence was only slightly increased during dialysis (n = 870; SIR, 1.35; 95% CI, 1.27-1.45) and before RRT (n = 689; SIR, 1.16; 95% CI, 1.08-1.25). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites. Most of these cancers were of known or suspected viral etiology.ConclusionsKidney transplantation is associated with a marked increase in cancer risk at a wide variety of sites. Because SIRs for most types of cancer were not increased before transplantation, immune suppression may be responsible for the increased risk. These data suggest a broader than previously appreciated role of the interaction between the immune system and common viral infections in the etiology of cancer.

9540 Background: Obesity (defined by body mass index, BMI≥30kg/m2) has been associated with adverse outcomes in postmenopausal women with breast cancer (BC). In premenopausal women the relationship is less clear. The impact of obesity on disease recurrence and death was studied in the population-based Australian Breast Cancer Family Study (ABCFS). Methods: 1108 early-stage BC patients, 47% diagnosed age< 40, were followed prospectively. Details on weight and height were collected by face-to-face interview at recruitment to the ABCFS. BC treatment and outcome data were abstracted from medical records. Ideal dose of chemotherapy was calculated and compared to actual dose received at cycle 1. The hazard ratio (HR) for disease recurrence and death associated with obesity was estimated using Cox proportional hazard survival models adjusting for number of axillary nodes, age, tumor size, grade and ER/PR at diagnosis. Results: Median follow-up was 5(0.4–10.8) years. 133 were obese. 75%(817/1108) were premenopaus...

Phenacetin and papillary necrosis: independent risk factors for renal pelvic cancer. A case—control study was undertaken to determine whether renal papillary necrosis (RPN) is an essential step in thc genesis of analgcsic—associated canccr of the renal pelvis (CaP). Kidneys of 66 patients (and 86 cases of renal parenchymal cancer (CaK), for comparison) were examined for evidence of RPN. Information concerning past consumption of phenacetin—containing analgesics (PhA) was obtained from all cases and 751 population controls by means of a questionnaire. Separately, RPN and regular consumption of PhA each conferred a relative risk for CaP of 3-1/2 to 7, while together they increased the risk some 20 times that for non-consumers without RPN. This suggests that each factor has independent, and when they coexist sequential, effects. The risk for CaK was doubled by regular PhA consumption but was not increased by RPN.

Data from the New South Wales (NSW) Central Cancer Registry comprising all new cases of cancer registered in persons aged 15 years and over for the 10-year period 1973 to 1982 were examined using log-linear regression to determine whether the incidence of cancer had been changing in NSW. Allowing for the altered age and sex structure of the population over this period, the annual incidence rate for all sites combined increased significantly by 1.7% in men and 1.0% in women. Cancers which had increased at a rate significantly greater than that for all sites combined were those of unknown primary site (8.7% per year), lung (in women only, 5.6%), kidney (4.5%), bladder (2.7%) and rectum (2.6%) and lymphomas (2.6%). Other cancers which showed a significantly increased incidence rate per se were testis (3.5%), larynx (3.2%), prostate (2.1%), colon (1.7%), brain (1.6%), leukaemias (1.3%) and lung (in men only, 0.7%). Cancers which had decreased significantly in incidence were those of oesophagus (-2.2%), cervix uteri (-2.0%) and stomach (-1.4%). No significant change in incidence over the 10 years had occurred for cancers of the corpus uteri, breast, ovary or pancreas.

Summary: Data from the New South Wales (NSW) Central Cancer Registry comprising all new cases of, and deaths from, invasive cancer of the cervix uteri registered in persons aged 15 years and over for the 10-year period 1973 to 1982 were examined using log-linear regression to determine whether incidence and mortality had been changing in NSW. Allowing for the estimated fraction of women who had undergone hysterectomy, this cancer had decreased significantly in incidence (- 1.3% per year) as well as mortality (-3.6%). There were no significant trends in relation to age at diagnosis, stage at diagnosis or histological type. Overall, younger age at diagnosis was associated with an earlier stage at presentation and there was no evidence for a trend towards more severe disease in young women during the 10-year period. No evidence was found for an increasing incidence of adenocarcinoma. By 1982 the age-standardized incidence rate was 10.4 per 100,000 (12.5 per 100,000 after adjustment for the hysterectomy fraction). Cancer of the cervix uteri was more common in Inner and Western Sydney and less common in the Northern Metropolitan region of Sydney and rural New South Wales.

A lifetime history of analgesics and tobacco consumption was obtained by a questionnaire completed at interview from 67 patients with carcinoma of the renal pelvis (40 women, 27 men) and 180 control subjects drawn from two sources, friends of patients and persons attending a health screening clinic. Regular consumption of analgesics conferred a tenfold relative risk of renal pelvic cancer in women and in men a risk ratio of 4-8. The fraction of cases for which analgesic consumption was an attributable risk was 0.74 in women and 0.43 in men. The effect of tobacco, much less than that of analgesics, was significant only in women (risk ratio approximately four; attributable risk 0.4), and no dose-response relationship was demonstrated. Relative excess risks suggested a synergistic effect when both analgesics and tobacco had been consumed. Standardized risk ratios indicated a dose-response relationship for both phenacetin-containing and non-phenacetin analgesics: moderate consumption doubled the risk of renal pelvic cancer, and heavy consumption increased at risk to 6-16 times that for noncomsumers.

In a case-control study of 36 men with cancer of the ureter and 307 male controls with the same age distribution tobacco smoking conferred a relative risk for this cancer of 2.9, whereas consumption of analgesics of any kind did not increase the risk. The relative risk for cancer of the renal pelvis, determined for 29 men, was 2.4 for tobacco and 6.0 for phenacetin-containing analgesics. Analgesics containing no phenacetin conferred no increased risk for cancer at this site. Data for 13 women with ureteral cancer, 5 of whom had taken phenacetin, are presented but not analyzed.

In a case-control investigation of 154 women with cancer of the bladder and 440 female population controls spanning the same age range, the relative risk for this cancer was 2.6 in consumers of phenacetin-containing analgesics and 2.7 in tobacco smokers. The relative risks for cancer of the renal pelvis, determined for 31 cases, were 5.4 with phenacetin and 4.7 with tobacco. Increasing consumption of either agent increased the risk for cancer at each of the two sites, while a synergistic rather than purely additive effect was apparent when both phenacetin-containing analgesics and tobacco had been taken. Consumption of analgesic preparations which contained no phenacetin did not increase the risk of developing cancer at either site. The evidence indicates that phenacetin is a clinically important carcinogen for the lower as well as for the upper urinary tract.

A case-control study of cancer of the renal parenchyma (360 cases and 985 controls) investigated lifestyle and dietary risk factors by means of a questionnaire survey. A lifetime history concerning urological disease and consumption of analgesics, tobacco, and prescribed medicines, was obtained together with current dietary and demographic information. Estimates of relative risk were calculated using logistic regression. Statistically significant associations were found with phenacetin-containing analgesics, urological disease and increasing consumption of milk. No association was found with consumption of aspirin, paracetamol, prescribed medicines, tea, coffee or animal proteins other than milk, or with the type of fat or oil used for cooking or spreading. The association with tobacco just failed to reach significance.

The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.

A population-based case-control study of incident primary malignant brain tumours diagnosed during 1985 to 1989 in children aged 0 to 14 years was carried out in the coastal conurbation of New South Wales comprising Sydney, Wollongong and Newcastle in the period 1988 to 1990. Personal interviews were conducted using a structured questionnaire with mothers of 82 cases and 164 control children individually matched to the cases by sex and age. Among the hypotheses being examined were those related to exposure to parental tobacco smoke, N-nitroso compounds and possible protection from sources of vitamin C. No link was found with tobacco smoking by the mother before or during pregnancy. While exposure during pregnancy of the mother to tobacco smoke of the father appeared to double the risk of childhood brain tumours and a similar risk was found for father (but not mother) smoking before the index pregnancy, there was no "dose-response" and the increased risk was confined to data supplied by the mother (rather than the father himself). The risk of childhood brain tumours rose with reported increasing consumption, during pregnancy, of cured meats, which have high levels of N-nitroso compounds (or their precursors), and fell with rising consumption of vegetables. No association was found between the risk of childhood brain tumours and family history of epilepsy, cancer, or tumours of the nervous system, parental irradiation, previous miscarriage or procedures carried out during pregnancy, maternal consumption of antihistamines, barbiturates or diuretics, or maternal contact with cats or farm-life during pregnancy.

This report notes the differences in the classification of the primary renal disease (PRD) used in different renal dialysis and transplant registries worldwide. The heterogeneity of coding systems complicates the comparative analysis of end-stage renal disease from different regions. Using data collected over two decades in the United States, Europe, and Australia/New Zealand, we present a method for reorganization of the classes of PRD that allows a straightforward comparison of retrospective data from these registries.

Background: The ATM gene encoding a putative protein kinase is mutated in ataxia-telangiectasia (A-T), an autosomal recessive disorder with a predisposition for cancer. Studies of A-T families suggest that female heterozygotes have an increased risk of breast cancer compared with non-carriers. However, neither linkage analyses nor mutation studies have provided supporting evidence for a role of ATM in breast cancer predisposition. Nevertheless, two recurrent ATM mutations, T7271G and IVS10-6T→G, reportedly increase the risk of breast cancer. We examined these two ATM mutations in a population-based, case-control series of breast cancer families and multiple-case breast cancer families. Methods: Five hundred twenty-five or 262 case patients with breast cancer and 381 or 68 control subjects, respectively, were genotyped for the T7271G and IVS10-6T→G ATM mutations, as were index patients from 76 non-BRCA1/2 multiple-case breast cancer families. Linkage and penetrance were analyzed. ATM protein expression and kinase activity were analyzed in lymphoblastoid cell lines from mutation carriers. All statistical tests were two-sided. Results: In case and control subjects unselected for family history of breast cancer, one case patient had the T7271G mutation, and none had the IVS10-6T→G mutation. In three multiple-case families, one of these two mutations segregated with breast cancer. The estimated average penetrance of the mutations was 60% (95% confidence interval [CI] = 32% to 90%) to age 70 years, equivalent to a 15.7-fold (95% CI = 6.4-fold to 38.0-fold) increased relative risk compared with that of the general population. Expression and activity analyses of ATM in heterozygous cell lines indicated that both mutations are dominant negative. Conclusion: At least two ATM mutations are associated with a sufficiently high risk of breast cancer to be found in multiple-case breast cancer families. Full mutation analysis of the ATM gene in such families could help clarify the role of ATM in breast cancer susceptibility.