Risk factors for adult renal cell carcinoma

By Robert Riley,2014-01-15 05:28
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Risk factors for adult renal cell carcinoma

    Risk factors for adult renal cell carcinoma: a systematic review

    and implications for prevention


    Renal cell cancer;risk factor;case-control studies;epidemiology


    RCC accounts for ? 3% of cancers in adults and ? 85% of all primary malignant kidney

    tumours. The incidence of RCC has been steadily increasing for several years. In France, the incidence of RCC according to cancer registers was 12 per 100 000 men and 6 per 100 000 women in 1995, and mortality rates were over 7.5 per 100 000 men and 4.0 per 100 000 women, similar to reports from other European countries [1,2].

    About half the cases of RCC diagnosed are currently discovered by chance during ultrasonography. This suggests that these tumours could be detected more frequently by simple imaging techniques at earlier stages of the disease, when surgical treatment is curative. The 5-year survival rate is 88100% for localized tumours but only 20% or less for metastatic tumours [3]. As

    patients with localized RCC survive longer than those with disseminated disease, it is likely that a screening programme for RCC would improve disease prognosis. However, in the absence of known high-risk populations, systematic early detection of RCC may not be cost-effective.

    Several potential risk factors for RCC have been identified in previous epidemiological studies. Discrepancies between these studies and the weakness of associations between various types of exposure and RCC make it difficult to identify unequivocally the true risk factors. We attempted to rank the most consistent associations and to define populations at high-risk of RCC by systematically reviewing published analytical epidemiological studies.


    We searched the Medline? database for studies published from 1987 to 1998, using a

    strategy including the following medical subject headings: heading ‘renal cell carcinoma’ and subheadings ‘risk factors’ or ‘epidemiology’. This screening was supplemented by manually searching for all the references from retrieved articles.

    To be included, epidemiological studies of RCC had to be cohort or case-control studies, and results had to be expressed as relative risk (RR) or odds ratio (OR), respectively, with 95% CI. A multivariate analysis had to have been performed to adjust for the main confounding variables. Only articles written in English about primary adenocarcinomas in adults were considered in the analysis. If an author(s) published several papers based on the same study, only data from the most recent publication were included. Studies of RCC occurring during dialysis or in transplant recipients were excluded.

    Method of analysis

    If several types of exposure were considered in a study, the results obtained were analysed for each of them separately. For each study, an association between an exposure and RCC was confirmed if the 95% CI for the RR or OR did not include unity. Such studies were defined as positive for this exposure. For each exposure, the number of studies relating to the association was counted. For each relevant study, the number of patients and controls, and the results expressed as RR or OR according to the level of exposure if possible, were recorded; any adjustment for confounding factors was also recorded.

    An exposure was considered to be a risk or protective factor if the following criteria were met [4]: an association was observed in more than half of the studies (consistency between studies); and a dose-dependent effect shown. If only the first criterion was met, the exposure was considered to be a risk marker. If neither criterion was met, the exposure was not considered to be associated with RCC.


    Of the 128 articles selected from the screening, 44 were considered relevant (36 case-control and eight cohort studies). These studies analysed the effects of tobacco use, obesity, kidney diseases, hypertension, drug intake, occupational factors, hormonal status, socio-economic status, alcohol, and coffee or tea intake.


    Ten case-control studies [514] and one cohort study [15] investigated the relationship

    between tobacco use and RCC. ORs were adjusted for age in all studies. Seven studies (Table 1)

    showed an association between tobacco smoking and RCC; the ORs were 1.39.3. In these studies,

    a dose-dependent effect was shown in men with a higher risk of RCC, proportional to tobacco consumption. Only consumption over 20 pack-years (PY) led to a significant association. For consumption of 2040 PY, ORs were 1.31.6, and for consumption of > 40 PY, ORs were 1.59.3;

    at < 20 PY, there was no increase in risk.

    YReferCases/controlTobacco Country OR (95% CI) *ear ence s (n/n) consumption

    ; *

    As kg tobacco or cigarette in pack-years.

    1Australi100249 kg 1.3 (0.91.9) 1.9 [9] 360/985 988 a ? 250 kg (1.32.7)

    1? 3 pack/day Men 1.7 (1.12.8) 1.7 [4] USA 203/605 990 Women (0.93.2)

    1[5] USA 90/91 Men > 20 PY 9.2 (2.145.2) 992

    YReferCases/controlTobacco Country OR (95% CI) *ear ence s (n/n) consumption

    1Men > 20 PY 2.2 (1.53.3) 2.2 [6] Canada 655/1536 993 Women > 20 PY (1.43.4)

    1DenmarMen > 40 PY 2.3 (1.15.1) 1.3 [10] 368/396 994 k Women > 40 PY (0.35.3)

    1GermanMen > 40 PY 2.15 (0.994.65) [12] 273/277 995 y Women > 40 PY 2.21 (0.726.81)

    1Australi[11] 1732/2309 20.236.9 PY 1.3 (1.01.6) 995 a,

    Denmar > 36.9 1.7 (1.42.1) k,

    German y, USA

    and Sweden.

    1Men > 40 PY 1.5 (1.22.1) 1.1 [13] USA 788/779 995 Women > 40 PY (0.61.8)

    Table 1. Risk of RCC from tobacco smoking according to tobacco consumption

    (dose-dependent response), from positive studies in a systematic review

    ORs were studied separately for both sexes in five studies [6,1014]; the association between

    tobacco consumption and RCC was significant only for men in four of them. Only one study showed an association between RCC and tobacco consumption in both women and men [6]. No

    risk from tobacco was shown for female heavy-smokers (> 40 PY) in the other studies. Only two studies showed no relationship between smoking and RCC [7,8]. However, in these studies,

    inpatients were used as controls and heavy smokers (> 40 PY) were not considered separately. Thus heavy smoking can be considered as a risk factor for RCC.


    The association between obesity and RCC was analysed in eight case-control studies [58,1619]. Weight was expressed as body mass index (BMI), calculated at various times in the subjects’ life (the year before diagnosis, at different 10-year intervals) or by comparison with

    normal adult weight. Only one study found no association between BMI and RCC [8], but BMI

    was not analysed separately in men and women. Another seven studies showed an association between obesity and RCC, with ORs of 1.14.6 (Table 2) [57,1619]. Obesity was identified as a

    risk factor for women in four studies [1619], and for both men and women in three others [57].

    YRefeCases/controls Men/woCountry OR (95% CI) ear rence (n/n) men

    YRefeCases/controls Men/woCountry OR (95% CI) ear rence (n/n) men

    1. NA, not available.

    1Men 2.4 (1.05.9) 3.5 [7] France 196/347 993