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Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics., (Copyright 2001 by W.B. Saunders Company.)

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.

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.

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.

In a population based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP), and 523 controls from the electoral roles were obtained about employment in certain industries or occupations, and exposure to particular chemicals chosen because of suspected associations with kidney cancer. A low level of education increased the risk for CaRP but not RCC. After adjustment for known risk factors, exposure to asbestos significantly increased the risk for RCC (relative risk (RR) = 1.62; 95% confidence interval (95% CI) 1.04-2.53). Working in the dry cleaning industry had a stronger link with CaRP (RR = 4.68; 95% CI 1.32-16.56) than with RCC (RR = 2.49; 95% CI 0.97-6.35). Working in the iron and steel industry doubled the risk for CaRP (RR = 2.13; 95% CI 1.04-4.39) whereas employment in the petroleum refining industry had a non-significant association with CaRP (RR = 2.60; 95% CI 0.88-7.63) and none with RCC.

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.

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).

In a population-based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls confirmed an increased risk associated with cigarette smoking in both types of cancer. The risk among current smokers was consistently higher than among ex-smokers, and was nearly twice as great for CaRP than for RCC. Additional information provided by this study includes reduced risks following cessation of smoking within 12 years for CaRP, but only after 25 years for RCC. Starting to smoke before, rather than after, the age of 18 years is linked independently with almost twice the risk for CaRP, but does not affect the risk for RCC. No independent trend was found with number of cigarettes smoked per day.