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N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (< or =5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring., ((c) 2005 Wiley-Liss, Inc.)

The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case-control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0-19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population-based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the child's age at diagnosis, the histologic type of tumor or center., (Copyright 2002 Wiley-Liss, Inc.)

Routinely collected data for New South Wales were used to analyse cancer mortality in migrants from the British Isles, southern Europe and eastern Europe according to duration of residence in Australia. A case-control approach compared deaths from cancer at one site with deaths from all other cancers, adjusting for age, sex and calendar period. Compared with the Australia-born, migrants had a significantly lower risk of dying from cancers of the mouth/pharynx and prostate (migrants from each region), colon/rectum (from the British Isles and southern Europe) and lung (female southern European migrants), evident from the time of migration and maintained for 30 years after migration. Whereas a deficit of deaths from colorectal cancer remained in migrants from southern Europe, a clear gradient of increasing risk with duration of stay in Australia was apparent. A similar trend was seen with respect to kidney cancer in southern European migrants. Persistent excess risks of death from stomach cancer were seen in all migrant groups, from lung cancer in British migrants and from liver cancer in southern and eastern European migrants. Although the risk of death from breast cancer increased significantly with duration in Australia in southern European migrants, the increase was not monotonic, as the relative risk in the first 10 years after migration was almost the same as that after more than 30 years. The pattern of risk for cancers of the prostate and mouth/pharynx suggests some protective role for inheritance or maintained cultural factors., (Copyright 1999 Wiley-Liss, Inc.)

To examine the use of mammographic screening in women in New South Wales (NSW), we measured uptake of initial mammograms and estimated the proportions of breast cancers that were screen detected. To see if mammographic screening has been associated with reductions in advanced breast cancers and mortality from breast cancer, we analyzed trends in age-specific and age-standardized breast cancer incidence and mortality from 1972 to 1995 and tumor size in 1986, 1989, 1992 and April to September 1995. Between 1984 and the end of 1995, an estimated 72% of NSW women in their 50s and 67% in their 60s had had at least 1 mammogram and, in 1995, an estimated 39% of invasive breast cancers in women in these age groups were detected by mammography. Before 1989, breast cancer incidence increased only slightly (+1.3% annually) but then, from 1990 to 1995, increased more rapidly (+3.1% annually). Between 1986 and 1995, rates of small cancers (< 1 cm) increased steeply by 2.7 times in women 40-49 years of age and 5.6 times in women 50-69 years of age. The incidence of large breast cancers (3+ cm), after little apparent change to 1992, fell by 17% in women 40-49 years of age and 20% in those 50-69 years of age to 1995. Breast cancer mortality increased slightly between 1972 and 1989 (+0.5% annually) but then fell (-2.3% annually) from 1990 to 1995. We concluded that breast cancer rates had been influenced in expected directions by the introduction of mammographic screening in women resident in NSW. We expect that recent falls in incidence of larger breast cancers and breast cancer mortality will become steeper as screening coverage increases in the second half of the 1990s.

There has been recent interest in the risk of various cancers in cystic fibrosis (CF) patients and carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. It has been proposed that a CFTR mutation may protect against breast cancer, based on evidence that elevated extracellular adenosine triphosphate (ATP) is known to inhibit breast cancer cell line growth and that CFTR pumps ATP out of epithelial cells. A CFTR mutation would therefore result in higher concentrations of serum ATP. A CFTR knockout mouse model had high serum concentrations of ATP and showed reduced breast tumour implantibility and decreased breast cancer growth rates. We have evaluated the relationship between the deltaF508 CFTR mutation and the risk of breast cancer before the age of 40. The deltaF508 CFTR mutation carrier rate in 272 cases (2.2%) was no different from the carrier rate observed in 171 controls (1.8%). If there was a protective effect resulting from the postulated elevation in serum ATP levels, tumours arising in deltaF508 CFTR carriers would have been expected to be generally less aggressive. When the histological features of the breast cancers with a deltaF508 CFTR mutation were reviewed and graded using a combined architectural and cytological grading system, all were found to be grade III, poorly differentiated tumours, contrary to the predictions. A combination of our data with other large population-based samples of cases and controls is required to resolve this issue.

Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-->T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.

A national population-based case-control study was used to assess the influence on breast cancer risk of reproductive factors and the possibility of an interaction with age at diagnosis. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. There was a declining risk of breast cancer with increasing age at menarche (p = 0.06), the strongest effect being seen in women aged less than 40. Parous women had a 27% lower risk of breast cancer than nulliparous women, a reduced risk being evident in all but the youngest age group. A falling risk of breast cancer with rising parity was clear only in women diagnosed when aged at least 45 years. Breast cancer risk tended to fall amongst parous women with increasing duration of breastfeeding (p = 0.14); the association was most apparent in the youngest women, while those over 40 years at diagnosis showed no clear negative trend. There was no association of breast cancer risk with age at first full-term pregnancy, time since last full-term pregnancy, abortion (spontaneous or induced), abortion before first full-term pregnancy, or ability to conceive, and there was no trend in risk with age at natural menopause. Women in the highest category of body mass index at age 20 had the lowest risk of breast cancer in the age group studied. When each reproductive factor was formally tested for effect modification by age at diagnosis, the interaction term in logistic models approached statistical significance only for parity (p = 0.07).

A national population-based case-control study was used to assess the influence on breast cancer risk of a family history of the disease and the possibility of an interaction with reproductive risk factors. A total of 891 women aged 25-54 years with a first diagnosis of breast cancer and 1,864 control subjects randomly selected from the electoral rolls were interviewed. Age-adjusted relative risks (RR) of breast cancer were similar for mothers (RR = 2.3) and sisters (RR = 2.7) but somewhat higher for first-degree (RR = 2.6) than for second-degree (RR = 1.7) relatives. Cases reporting a first- or second-degree relative with breast cancer were no more likely to be diagnosed at an early age than those with no family history. With regard to the age at diagnosis of the relative, the RR was higher if breast cancer had been diagnosed before the age of 45 years than later; this was true for first-degree as well as for second-degree relatives. In women with no family history, the falling RRs with increasing age at menarche reflected the usual pattern, but no such trend was apparent in those reporting a mother or sister with breast cancer. For age at first full-term pregnancy, parity, breast-feeding, menopausal status, infertility, history of benign breast disease and body mass index, no evidence was seen of effect modification by a family history of breast cancer. Mothers of cases had about twice the cumulative rate of breast cancer as mothers of controls, a similar difference being seen between sisters of cases and sisters of controls.

A number of medical conditions have been linked with renal-cell cancer, although the evidence is not consistent in every case. In a large international case-control study of renal-cell cancer, we examined, among other hypotheses, associations with a personal history of certain medical conditions and a family history of cancer of the kidney or thyroid. Relative risks (RR), adjusted for the effects of age, gender, body-mass index, tobacco smoking and study centre, were significantly increased by a history of kidney stones or thyroid or kidney disease. The RR were not altered by additional adjustment for hypertension, or when diagnoses were restricted to those made at least 5 or 10 years before 1987 (the usual "cut-off" date). The link with kidney injury is particularly likely to be affected by recall bias. Increased RR of borderline significance were found for kidney infection (RR, 1.2) and diabetes (RR, 1.4). Having one first-degree relative with kidney cancer was associated with a significantly increased risk of renal-cell cancer (RR, 1.6; 95% Cl, 1.1-2.4). Seven cases reported 2 first-degree relatives with kidney cancer. No controls had first-degree relatives with kidney cancer. None of our participants reported having von Hippel-Lindau disease. The data suggests that a few conditions of the kidney are strongly associated with renal-cell cancer and that heredity plays a role in a small proportion of cases.

The standard high-range activated clotting time (sHR ACT) is used to monitor anticoagulation postangioplasty (PTCA), but may be unreliable. We assessed the accuracy of a new method we termed the ACT differential (ACT Diff), obtained by measuring the difference between an sHR ACT and a heparinase ACT from the same sample. Heparinase removes heparin from its sample and provides a current heparin-free baseline. For phase 1 of the study, the sHR ACT, ACT Diff, and laboratory APTT were measured in 250 samples from 75 PTCA patients. In 125 samples with an APTT prolonged but within measurement range, linear regression against the APTT was performed. The correlation coefficient was 0.74 for the ACT Diff and 0.24 for the sHR ACT. An ACT Diff of 15-25 sec was found to equal an APTT of 2.5-3.5 x control. In 50 samples with a normal activated partial thromboplastin time (APT), there was good differentiation by the ACT Diff of results from those adequately heparinized, with a value of 0.9 +/- 4.4 sec. The sHR ACT was 114 +/- 15.5 sec, and could not reliably distinguish between anticoagulated and nonanticoagulated samples. In 75 samples obtained with a high APTT (above measurement range), the ACT Diff was > 30 sec in 95% of samples, and again this allowed differentiation from therapeutic samples. The equivalent sHR ACT was 148 sec, and could not reliably distinguish between anticoagulated and overanticoagulated samples as the ACT Diff could. In phase 2, to examine the clinical usefulness of the ACT Diff, 286 patients were managed post-PTCA by starting heparin when ACT Diff fell to < 50 sec, maintaining ACT Diff at 15-25 sec during heparin infusions, and following cessation of heparin, by removing sheaths when the ACT Diff was < 7 sec. These patients were compared to a control group of 250 patients. Major bleeding (5% vs. 0.5%, P < 0.005) and minor bleeding (30% vs. 13%, P < 0.001) were significantly reduced in the group managed using the ACT Diff. The reduction in bleeding was thought to be due to the rapid availability of reliable results. Abrupt closure was low in both groups (0% with ACT Diff vs. 0.8%). No other thrombotic events occurred. Following phases 1 and 2, the ACT Diff replaced the APTT in all PTCA patients at this institution. In the 18 mo from July 1993, 1,104 patients were managed this way. Incidence of major bleeding (0.2%), transfusion requirement (0.1%), false anneurysm (0.6%), and abrupt closure during heparin infusion (0.1%) remained low. In conclusion, the ACT Diff is more accurate than an sHR ACT, and its clinical use in PTCA patients is associated with a very low incidence of complications from anticoagulation. Its routine use should be considered by units unable to obtain rapid APTT results.

We investigated the role of diet in the etiology of renal cell cancer (RCC) in a multi-center, population-based case-control study conducted in Australia, Denmark, Sweden and the United States, using a shared protocol. A total of 1,185 incident histopathologically confirmed cases (698 men, 487 women) and 1,526 controls (915 men, 611 women) frequency-matched to cases by sex and age were included in the analyses. The association between RCC and diet was estimated by relative risks (RR) and 95% confidence intervals (CI) adjusted for age, sex, study center, body mass index and smoking. A statistically significant positive association was observed for total energy intake (RR = 1.7, 95% CI = 1.4-2.2 for the highest vs. lowest quartile, p value for trend < 0.00001), while the hypothesis that protein and fat are risk factors independent of energy was not supported. Fried meats were associated with increased RCC risk, while vegetables and fruits were protective, with the strongest effect observed for the highest quartile of consumption of orange/dark green vegetables but not vitamin C or beta carotene. Increased risk was associated with low intake (lowest decile) of vitamin E and magnesium. We observed an apparent protective effect of alcohol confined to women and probably due to chance. Our findings indicate an important role of nutrition in the development of RCC. The apparent positive association of energy intake with risk of RCC needs further investigation in a prospective cohort study to exclude the possible impact of differences in recall between cases and controls.

Risk of renal-cell cancer in relation to use of diuretics, other anti-hypertensive medications and hypertension was assessed in a multi-center, population-based, case-control study conducted in Australia, Denmark, Germany, Sweden and the United States, using a shared protocol and questionnaire. A total of 1,732 histologically confirmed cases and 2,309 controls, frequency-matched to cases by age and sex, were interviewed. The association between renal-cell cancer and the drugs was estimated by relative risks (RRs) and 95% confidence intervals (CIs). Risks were increased among users of diuretics and other anti-hypertensive medications. After adjustment for hypertension, risk for diuretics was reduced to unity, except among long-term (15+ years) users. Risk for use of non-diuretic anti-hypertensive drugs remained significantly elevated and increased further with duration of use. Overall risk was not enhanced when both classes of medications were used. Excess risk was not restricted to any specific type of diuretic or anti-hypertensive drug and no trend was observed with estimated lifetime consumption of any particular type of product. The RR for hypertension after adjustment for diuretics and other anti-hypertensive medications was 1.4 (95% CI = 1.2-1.7), although among non-users of any anti-hypertensive medications, there was little excess risk associated with a history of hypertension. Exclusion of drug use that first occurred within 5 years of cancer diagnosis or interview did not alter the associations. Our findings suggest small effects on renal-cell cancer risk associated with hypertension and use of diuretics and other anti-hypertensive medications. However, because of potential misclassifications of these highly correlated variables, it is difficult to distinguish the effect of treatment from its indication, hypertension.

The relationship between renal-cell cancer (RCC) and occupation was investigated in an international multicenter population-based case-control study. Study centers in Australia, Denmark, Germany, Sweden and the United States interviewed 1732 incident RCC cases and 2309 controls. Significant associations were found with employment in the blast-furnace or the coke-oven industry [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1-2.7], the iron and steel industry (RR, 1.6; 95% CI, 1.2-2.2) and exposure to asbestos (RR, 1.4; 95% CI, 1.1-1.8), cadmium (RR, 2.0; 95% CI, 1.0-3.9), dry-cleaning solvents (RR, 1.4; 95% CI, 1.1-1.7), gasoline (RR, 1.6; 95% CI, 1.2-2.0) and other petroleum products (RR, 1.6; 95% CI, 1.3-2.1). Asbestos, petroleum products and dry-cleaning solvents appear to merit further investigation, in view of the relationship between risk and duration of employment or exposure and after adjustment for confounding. There was a negative association between RCC and education, but it was not consistent across all centers. Overall, the results of our multicenter case-control study suggest that occupation may be more important in the etiology of RCC than indicated by earlier studies.

The relationships between reproductive factors, exogenous hormones and renal-cell cancer were examined in an international, multicenter, population-based, case-control study undertaken in 1989-1991. Data from 5 centers situated in Australia, Denmark, Germany, Sweden and the United States included for analysis 608 women with renal-cell cancer and 766 female controls. A significant trend in risk (p = 0.002) was associated with number of births, with an 80% excess risk for 6 or more births [RR = 1.8, 95% confidence interval (CI) = 1.1 to 2.9] compared with one birth. A decreasing risk was seen for increasing age at first birth, although this was confounded by body-mass index and number of births. A suggestive reduction of risk was also seen for increasing age at menarche. Age at menopause was unrelated to risk of renal-cell cancer. An increased risk was observed for women having had both a hysterectomy and an oophorectomy. Use of oral contraceptives in non-smoking women reduced the risk of renal-cell cancer (RR = 0.5, 95% CI = 0.4 to 0.8); this reduction increased with longer duration of use. No association was observed for estrogen replacement therapy. Our results indicate that certain hormonal and reproductive variables may be related to risk of renal-cell cancer and deserve further investigation, both epidemiologically and experimentally.

There has been concern about the role of analgesics in the development of renal-cell cancer, although a few studies have reported moderately elevated risks with regular or long-term use. In a large international case-control study of renal-cell cancer we examined, among other hypotheses, the effect of phenacetin-containing and of other types of analgesics: paracetamol (acetaminophen), salicylates (mainly aspirin) and pyrazolones (e.g., antipyrine or phenazone). Relative risks, adjusted for the effects of age, sex, body-mass index, tobacco smoking and study centre, were not significantly increased with intake of phenacetin, either when lifetime consumption was categorized at the level of > or = 0.1 kg or when subjects were subdivided further by amount. Nor were paracetamol, salicylates or pyrazolones linked with renal-cell cancer. No consistently increasing risks with consumption level was found. The lack of association was not altered by restricting analgesic use to that which occurred 5 or 10 years before the defined "cut-off" date or when analysis was restricted to exclusive users of a particular type of analgesic. Neither was the risk influenced by the rate of consumption or whether the consumption had occurred at a young age. Our study provides clear evidence that aspirin is unrelated to renal-cell cancer risk, and our findings do not support the hypothesis that analgesics containing phenacetin or paracetamol increase the risk, although the number of "regular" users and the amount of these types of analgesic consumed were too small to confidently rule out a minor carcinogenic effect of phenacetin and paracetamol.

Although numerous studies have identified obesity or high relative weight as a risk factor for renal-cell cancer in women, the degree to which this effect is present in men remains unclear. A multicenter population-based case-control study concerning incident cases of histologically verified renal-cell cancer (n = 1,732) and age- and sex-matched controls (n = 2,309) was conducted in Australia, Denmark, Germany (2 centers), Sweden and the United States. Relative weight was estimated by the body mass index, and the association between this factor and other factors, such as height, physical activity and use of amphetamines, was measured by the relative risk estimated in logistic regression models. Body mass index was found to be a risk factor among women and, to a lesser extent, among men. A 3-fold increased risk (RR = 3.6, 95% CI = 2.3-5.7) was observed for women with a relative weight in the top 5% compared with those in the lowest quartile. Rate of weight change (estimated as weight change per annum in kilograms) appeared to be an independent risk factor among women but not among men. Physical activity and height were unrelated to risk of renal-cell cancer regardless of level of BMI, while use of amphetamines was associated with an increased risk among men, although no dose or duration effect was seen. Our findings verify the link between high relative weight and risk of renal-cell cancer, particularly among women. The mechanism that underlies this association is, however, still unclear, although the rate of weight change may play a role.

This report has the dual purpose of describing patterns of cancer incidence among adolescents in New South Wales (NSW), Australia, and comparing adult and childhood cancer classification schemes. All cases of cancer incident between 1972 and 1991 in NSW residents aged 10-19 years were obtained from the population-based NSW Central Cancer Registry and coded according to Birch and Marsden (1987) in addition to routine coding by the Ninth Revision of the International Classification of Diseases. The average incidence rate for all cancers combined was 158 and 140 per million in males and females respectively. The Birch and Marsden category of "carcinomas and other epithelial neoplasms" comprised 22% of all cancers in male adolescents and 37% in females. Melanoma alone accounted for 16% of all cancers in males and 26% in females. Rates of leukaemias and central nervous system tumours were similar in the age groups 10-14 years and 15-19 years. By contrast, lymphomas, bone tumours (males only), soft tissue (males only), "germ-cell, trophoblastic and other gonadal tumours" and "carcinomas and other epithelial neoplasms" were more common in the older age group. The Birch and Marsden classification with its emphasis on morphology provided a clearer picture of some types of cancer which occurred frequently among teenagers. Cancers common in adults did occur in older adolescents but were less well described by the childhood scheme. Cancers of colon and lung were often of unusual histological type compared to adult tumours. It would appear appropriate to use the childhood classification scheme to describe cancer incidence in adolescent age groups, perhaps with minor modification.

The relationship between renal-cell cancer (RCC) and tobacco use was investigated in an international, multicenter, population-based case-control study. Coordinated studies were conducted in Australia, Denmark, Germany, Sweden and the United States using a shared protocol and questionnaire. A total of 1,732 cases (1,050 men, 682 women) and 2,309 controls (1,429 men, 880 women) were interviewed for the study. No association was observed between risk and use of cigars, pipes or smokeless tobacco. A statistically significant association was observed for cigarette smoking, with current smokers having a 40% increase in risk [relative risk (RR) = 1.4, 95% confidence interval (CI) 1.2-1.7]. Risk increased with intensity (number of cigarettes) and duration (years smoked). Among current smokers the RR for pack-years rose from 1.1 (95% CI 0.8-1.5) for < 15.9 pack years to 2.0 (95% CI 1.6-2.7) for > 42 pack years (p for trend < 0.001). Long-term quitters (> 15 years) experienced a reduction in risk of about 15-25% relative to current smokers. Those who started smoking late (> 24 years of age) had about two-thirds the risk of those who started young (< or = 12 years of age). Overall, the findings of this pooled analysis confirm that cigarette smoking is a causal factor in the etiology of RCC.

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.

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.

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.

Cancer incidence in migrants to New South Wales (NSW) from the British Isles, north-central, eastern and southern Europe, the Middle East and Asia has been compared with that in Australian-born residents using data from the NSW Central Cancer Registry for 1972-84. Indirectly standardized incidence ratios (SIRs) were low in migrants from all 6 regions for melanoma of skin and cancers of lip and, except in men from eastern Europe, colon. Oesophageal, rectal and prostatic cancers also tended to be relatively less common. Cancers which were more common than in the Australian-born were those of the stomach and, for men, bladder (except in the Asian-born). Migrants from different regions showed variations from the cancer pattern of the Australian-born population which, for the most part, were predictable from the known incidence of cancer in the countries within the region of origin. Exceptions were the high relative incidence of nasopharyngeal cancer in migrants from southern Europe and bladder cancer in men from all regions other than Asia.

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.

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.