Increased Risk Of Renal Cell Cancer Research Articles

Lifetime body weight trajectories and risk of renal cell cancer: a large US prospective cohort study.

Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess bodyweight. Using the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N=138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: 1) BMI at specific ages; 2) adulthood BMI trajectories; 3) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and 4) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC. A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared to individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight (HR:1.49, 95%CI:1.19,1.87), from normal BMI to obesity (HR:2.22, 95%CI:1.70,2.90), and from overweight to obesity (HR:2.78, 95%CI:1.81,4.27). Compared to individuals who were never overweight (WYO=0), elevated HRs were observed among individuals who experienced low (HR:1.31, 95%CI:0.99,1.74), medium (HR:1.57, 95%CI:1.20,2.05), and high (HR:2.10, 95%CI:1.62,2.72) WYO tertile. Weight gain of ≥10kg was associated with increased RCC incidence for each age span. Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk. It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.

Reproductive and external hormonal factors and the risk of renal cell cancer in the Netherlands Cohort Study

BackgroundSeveral reproductive and hormonal factors, like age at menarche, parity, age at menopause, use of oral contraceptives and postmenopausal treatment, have been associated with the risk of renal cell cancer (RCC) in women, but results have not always been consistent. We therefore investigated the association between these factors and the risk of RCC in postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. MethodsInformation on reproductive history, exogenous hormone use and gynecological surgery was obtained through a self-administered questionnaire at baseline in 1986. After 20.3 years of follow-up, 204 cases and 2280 subcohort members were available for case-cohort analysis. Multivariable hazard ratios (HR) were calculated using Cox Proportional Hazard analysis. ResultsWomen who reported a hysterectomy had an increased RCC risk compared to women who did not (HR, 1.42, 95%CI, 1.01–2.00). Women with a natural age at menopause between 45 and 49 years compared to 50–54 years had an increased RCC risk (HR, 1.61; 95%CI, 1.10–2.35). RCC risk was slightly and not statistically significant increased among parous women with three or more children and age at first birth before 25 years compared to nulliparous women (HR, 1.36; 95% confidence interval (CI), 0.84–2.20). No associations were observed with RCC risk for age at menarche, use of oral contraceptives and use of hormonal replacement therapy. ConclusionHysterectomy and age at natural menopause were associated with an increased RCC risk. Other hormonal and reproductive factors and RCC risk were not increased. Further studies are required to establish the mechanism(s) that explain the observed association.

Coffee intake and trace element blood concentrations in association with renal cell cancer among smokers.

To determine whether higher coffee intake may reduce the risk of renal cell cancer (RCC) associated with lead (Pb) and other heavy metals with known renal toxicity. We conducted a nested case-control study of male smokers (136 RCC cases and 304 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cases diagnosed with RCC at 5 or more years following cohort enrollment were matched to controls on age (± 7years) and whole blood draw date (± 30days). Conditional logistic regression (using two-sided tests) was used to test for main effects and additive models of effect modification. After a mean follow-up of 16.3years, coffee consumption was not significantly associated with renal cell cancer risk, when adjusting for blood concentrations of Cd, Hg, and Pb and RCC risk factors (age, smoking, BMI, and systolic blood pressure) (p-trend, 0.134). The association with above median blood Pb and RCC (HR = 1.69, 95% CI 1.06, 2.85) appeared to be modified by coffee consumption, such that RCC risk among individuals with both increased coffee intake and higher blood lead concentration were more than threefold higher RCC risk (HR = 3.40, 95% CI 1.62, 7.13; p-trend, 0.003). Contrary to our initial hypothesis, this study suggests that heavy coffee consumption may increase the previously identified association between higher circulating lead (Pb) concentrations and increased RCC risk. Improved assessment of exposure, including potential trace element contaminants in coffee, is needed.

The association between hepatitis C virus infection and renal cell cancer, prostate cancer, and bladder cancer: a systematic review and meta-analysis

To update the current evidence on whether hepatitis C virus (HCV) infection represents a possible risk factor for renal cell cancer (RCC), prostate cancer (PCa), and bladder cancer (BC). We searched the literature on Pubmed, Web of Science, and Embases before April 2021. A systematic review and meta-analysis were performed. Finally, we extracted 12 studies based on the eligible criteria. Across 11 studies for HCV and RCC, the incorporated RR was 1.28 (95% CI 1.05–1.55), which meant that participants with HCV infection were associated with higher RCC risk. The pooled RR in hazard ratio (HR) subgroup (HR 1.59, 95% CI 1.22–2.08), cohort studies subgroup (RR 1.47, 95% CI 1.18–1.82), and North America subgroup (RR 1.71, 95% CI 1.40–2.09) detected a stronger association between HCV and RCC risk. Although an inverse association was seen for PCa (RR 0.75, 95% CI 0.54–1.03) across seven studies, it was not statistically significant (P = 0.075). There was no significant association between HCV and BC with an incorporated RR of 0.92 (95% CI, 0.82–1.03) across five studies. Our study demonstrated that HCV infection was significantly associated with increased RCC risk. There appeared to be an inverse association for HCV in PCa risk but not statistically significant. No significant association was found between HCV and BC risk. Prospective, large-scale, and well-designed cohort studies are required to validate the association between HCV and RCC, and to investigate the role of HCV on PCa.

Association between ACYP2 polymorphisms and the risk of renal cell cancer.

BackgroundKidney cancer is the predominant form of malignancy of the kidney and accounts for approximately 3%–4% of all cancers. Renal cell cancer (RCC) represents more than 85% of kidney cancer. It has been reported that genetic factors may predispose individuals to RCC. This study evaluated the association between Acylphosphatase 2 (ACYP2) gene polymorphisms and RCC risk in the Han Chinese population.MethodsTwelve single‐nucleotide polymorphisms (SNPs) in ACYP2 were genotyped using the Agena MassARRAY platform from 293 RCC patients and 495 controls. The Chi‐squared test, genetic models, haplotype, and stratification analyses were used to evaluate the association between SNPs and the risk of RCC. The relative risk was estimated using the odds ratio (OR) and 95% confidence interval (CI).ResultsWe observed that the rs6713088 allele G (OR = 1.26, 95% CI: 1.03–1.53, p = .023) and rs843711 allele T (OR = 1.29, 95% CI: 1.06–1.57, p = .010) were associated with increased RCC risk. Genetic model analyses found that rs843711 was significantly associated with an increased RCC risk under the recessive model and log‐additive model after adjusting for age and gender. Haplotype analysis showed that the haplotype “TTCTCGCC” (OR = 0.67, 95% CI: 0.48–0.94, p = .021) was associated with a decreased risk of RCC in the Han Chinese population. Stratification analysis also found that rs6713088 and rs843711 were significantly associated with increased RCC risk.ConclusionIn summary, the results suggested that ACYP2 polymorphisms could be used as a genetic marker for RCC. Additional functional and association studies are required to validate our results.

Polymorphisms in genes of the renin-angiotensin-aldosterone system and renal cell cancer risk: interplay with hypertension and intakes of sodium, potassium and fluid.

Hypertension is an established risk factor for renal cell cancer (RCC). The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is closely linked to hypertension. RAAS additionally influences homeostasis of electrolytes (e.g. sodium and potassium) and fluid. We investigated single nucleotide polymorphisms (SNPs) in RAAS and their interactions with hypertension and intakes of sodium, potassium and fluid regarding RCC risk in the Netherlands Cohort Study (NLCS), which was initiated in 1986 and included 120,852 participants aged 55 to 69 years. Diet and lifestyle were assessed by questionnaires and toenail clippings were collected. Genotyping of toenail DNA was performed using the SEQUENOM® MassARRAY® platform for a literature-based selection of 13 candidate SNPs in seven key RAAS genes. After 20.3 years of follow-up, Cox regression analyses were conducted using a case-cohort approach including 3,583 subcohort members and 503 RCC cases. Two SNPs in AGTR1 were associated with RCC risk. AGTR1_rs1492078 (AA vs. GG) decreased RCC risk [hazard ratio (HR) (95% confidence interval (CI)): 0.70(0.49-1.00)], whereas AGTR1_rs5186 (CC vs. AA) increased RCC risk [HR(95%CI): 1.49(1.08-2.05)]. Associations were stronger in participants with hypertension. The RCC risk for AGT_rs3889728 (AG + AA vs. GG) was modified by hypertension (p interaction = 0.039). SNP-diet interactions were not significant, although HRs suggested interaction between SNPs in ACE and sodium intake. SNPs in AGTR1 and AGT influenced RCC susceptibility, and their effects were modified by hypertension. Sodium intake was differentially associated with RCC risk across genotypes of several SNPs, yet some analyses had probably inadequate power to show significant interaction. Results suggest that RAAS may be a candidate pathway in RCC etiology.

A potentially functional polymorphism in the promoter region of miR-34b/c is associated with renal cell cancer risk in a Chinese population

Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.

Long-term dietary sodium, potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer

Background:As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC.Methods:The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses.Results:Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02).Conclusion:Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.

A Functional Variant in the MTOR Promoter Modulates Its Expression and Is Associated with Renal Cell Cancer Risk

BackgroundThe mTOR signaling pathway plays a crucial role in the carcinogenesis of renal cell cancer (RCC). We sought to investigate the influence of genetic variations in the mTOR pathway-related genes on the risk of RCC.MethodsWe genotyped 8 potentially functional polymorphisms in AKT1, AKT2, PTEN and MTOR genes using the TaqMan method in a case-control study of 710 RCC patients and 760 cancer-free subjects. Unconditional logistic regression, adjusted for potential confounding factors, was used to assess the risk associations. We then examined the functionality of the important polymorphisms.ResultsOf the 8 polymorphisms, after adjusting for multiple comparisons, we found a significant association between one variant (rs2295080) in the promoter of MTOR and reduced RCC risk (P = 0.005, OR = 0.74, 95%CI = 0.59–0.91, TG/GG vs. TT). Another variant (rs701848) in the 3′UTR region of PTEN was associated with increased RCC risk (P = 0.014, OR = 1.45, 95%CI = 1.08–1.96, CC vs. TT); however, the association was not significant after adjusting for multiple comparisons. Furthermore, we observed lower MTOR mRNA levels in the presence of the rs2295080G allele in normal renal tissues. The luciferase reporter assay showed that the rs2295080G allele significantly decreased luciferase activity. No other significant association between the selected polymorphisms and RCC risk was observed.ConclusionsOur results suggest that the functional MTOR promoter rs2295080 variant affects RCC susceptibility by modulating the endogenous MTOR expression level. The risk effects and the functional impact of the MTOR rs2295080 variant need further validation.

Prospective evaluation of analgesic use and risk of renal cell cancer.

Epidemiologic data suggest that analgesic use increases the risk of renal cell cancer (RCC), but few prospective studies have been published. We investigated the association between analgesic use and RCC in 2 large prospective studies. We examined the relationship between analgesic use and RCC risk in the Nurses' Health Study and the Health Professionals Follow-up Study. Use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen was ascertained in 1990 in the Nurses' Health Study and in 1986 in the Health Professionals Follow-up Study, and every 2 years thereafter. We evaluated baseline and duration of use of analgesics. During follow-up of 16 years among 77,525 women and 20 years among 49,403 men, we documented 333 RCC cases. Aspirin and acetaminophen use were not associated with RCC risk. However, regular use of nonaspirin NSAIDs was associated with an increased RCC risk; the pooled multivariate relative risk was 1.51 (95% confidence interval, 1.12-2.04) at baseline. The absolute risk differences for users vs nonusers of nonaspirin NSAIDs were 9.15 per 100 000 person-years in women and 10.92 per 100,000 person-years in men. There was a dose-response relationship between duration of nonaspirin NSAID use and RCC risk; compared with nonregular use, the pooled multivariate relative risks were 0.81 (95% confidence interval, 0.59-1.11) for use less than 4 years, 1.36 (0.98-1.89) for 4 to less than 10 years, and 2.92 (1.71-5.01) for use for 10 or more years (P < .001 for trend). Our prospective data suggest that longer duration of use of nonaspirin NSAIDs may increase the risk of RCC.

International renal cell cancer study. VII. Role of diet.

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.

International renal cell cancer study. VII. role of diet

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 β 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. © 1996 Wiley-Liss, Inc.