Risk Factors For Renal Cell Carcinoma Research Articles

Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma

We performed a series of integrative analyses including transcriptome-wide association studies (TWASs) and proteome-wide association studies (PWASs) of renal cell carcinoma (RCC) to nominate and prioritize molecular targets for laboratory investigation. On the basis of a genome-wide association study (GWAS) of 29,020 affected individuals and 835,670 control individuals and prediction models trained in transcriptomic reference models, our TWAS across four kidney transcriptomes (GTEx kidney cortex, kidney tubules, TCGA-KIRC [The Cancer Genome Atlas kidney renal clear-cell carcinoma], and TCGA-KIRP [TCGA kidney renal papillary cell carcinoma]) identified 38 gene associations (false-discovery rate <5%) in at least two of four transcriptomic panels and identified 12 genes that were independent of GWAS susceptibility regions. Analyses combining TWAS associations across 48 tissues from GTEx identified associations that were replicable in tumor transcriptomes for 23 additional genes. Analyses by the two major histologic types (clear-cell RCC and papillary RCC) revealed subtype-specific associations, although at least three gene associations were common to both subtypes. PWAS identified 13 associated proteins, all mapping to GWAS-significant loci. TWAS-identified genes were enriched for active enhancer or promoter regions in RCC tumors and hypoxia-inducible factor binding sites in relevant cell lines. Using gene expression correlation, common cancers (breast and prostate) and RCC risk factors (e.g., hypertension and BMI) display genetic contributions shared with RCC. Our work identifies potential molecular targets for RCC susceptibility for downstream functional investigation.

The DDD score outperforms the RENAL score in predicting high-grade renal cell carcinoma.

To explore the relationship between Fuhrman grade of renal cell carcinoma (RCC) and the DDD score. We reviewed the records of 527 nonmetastatic RCC patients. Demographic, clinical, and pathologic characteristics were reviewed. Binary logistic regression was used to explore the independent risk factors for high-grade RCC (HGRCC). Sex, BMI (Body Mass Index), RNS, and DDD score were significantly correlated with HGRCC. Based on these independent risk factors, we constructed two predictive models integrating the RNS and DDD scores with sex and BMI to predict tumor grade. The calibration curves of the predictive model showed good agreement between the observations and predictions. The concordance indexes (C-indexes) of the predictive models were 0.768 (95% CI, 0.713-0.824), and 0.809 (95% CI, 0.759-0.859). Receiver operating characteristic (ROC) curves were performed to compare the predictive power of the nomograms, and the prediction model including the DDD score had better prognostic ability (p = 0.01). This study found that RNS, DDD score, BMI, and sex were independent predictors of HGRCC. We developed effective nomograms integrating the above risk factors to predict HGRCC. Of note, the nomogram including the DDD score achieves better prediction ability for HGRCC.

Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993–2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, ORcontinuous = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), Ptrend = 0.04; ORcontinuous = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [ORcontinuous = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.

Kidney Function and Risk of Renal Cell Carcinoma.

We evaluated the temporal association between kidney function, assessed by estimated glomerular filtration rate (eGFR), and the risk of incident renal cell carcinoma (RCC). We also evaluated whether eGFR could improve RCC risk discrimination beyond established risk factors. We analyzed the UK Biobank cohort, including 463,178 participants of whom 1,447 were diagnosed with RCC during 5,696,963 person-years of follow-up. We evaluated the temporal association between eGFR and RCC risk using flexible parametric survival models, adjusted for C-reactive protein and RCC risk factors. eGFR was calculated from creatinine and cystatin C levels. Lower eGFR, an indication of poor kidney function, was associated with higher RCC risk when measured up to 5 years prior to diagnosis. The RCC HR per SD decrease in eGFR when measured 1 year before diagnosis was 1.26 [95% confidence interval (95% CI), 1.16-1.37], and 1.11 (95% CI, 1.05-1.17) when measured 5 years before diagnosis. Adding eGFR to the RCC risk model provided a small improvement in risk discrimination 1 year before diagnosis with an AUC of 0.73 (95% CI, 0.67-0.84) compared with the published model (0.69; 95% CI, 0.63-0.79). This study demonstrated that kidney function markers are associated with RCC risk, but the nature of these associations are consistent with reversed causality. Markers of kidney function provided limited improvements in RCC risk discrimination beyond established risk factors. eGFR may be of potential use to identify individuals in the extremes of the risk distribution.

Renal Abscess Complicated by Renal Vein Thrombosis Mimicking Clinical Stage T3a Renal Cell Carcinoma

Renal abscesses accompanied by a renal vein thrombosis (RVT) may have a similar appearance to clinical stage T3a renal cell carcinoma (RCC) on computed tomography (CT) imaging. RVTs are rare clinical findings that more commonly occur in adults with malignant renal tumors or nephrotic syndrome. A 71-year-old woman with risk factors for both renal infection and RCC was found to have a heterogeneous mass with irregular borders and areas of contrast enhancement on CT imaging. A two-week course of antibiotic and anti-coagulant treatment was prescribed with close follow-up. Urine culture eventually grew greater than 100,000 colonies of Escherichia coli. Repeat imaging after six weeks revealed resolution of the mass and the RVT. This patient's case emphasizes that although the findings of RVT and renal mass more commonly point to the diagnosis of malignancy, infections many present in a similar manner but require substantially different treatment. Close follow-up with repeat imaging is imperative to differentiate malignancy from infection or other causes.

Effect of smoking, hypertension and lifestyle factors on kidney cancer - perspectives for prevention and screening programmes.

Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated.

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018).

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n=453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.

MiT/TFE Family Renal Cell Carcinoma.

The microphthalmia-associated transcription factor/transcription factor E (MiT/TFE) family of transcription factors are evolutionarily conserved, basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors, consisting of MITF, TFEB, TFE3, and TFEC. MiT/TFE proteins, with the exception of TFEC, are involved in the development of renal cell carcinoma (RCC). Most of the MiT/TFE transcription factor alterations seen in sporadic RCC cases of MiT family translocation renal cell carcinoma (tRCC) are chimeric proteins generated by chromosomal rearrangements. These chimeric MiT/TFE proteins retain the bHLH-Zip structures and act as oncogenic transcription factors. The germline variant of MITF p.E318K has been reported as a risk factor for RCC. E 318 is present at the SUMOylation consensus site of MITF. The p.E318K variant abrogates SUMOylation on K 316, which results in alteration of MITF transcriptional activity. Only a few cases of MITF p.E318K RCC have been reported, and their clinical features have not yet been fully described. It would be important for clinicians to recognize MITF p.E318K RCC and consider MITF germline testing for undiagnosed familial RCC cases. This review outlines the involvement of the MiT/TFE transcription factors in RCC, both in sporadic and hereditary cases. Further elucidation of the molecular function of the MiT/TFE family is necessary for better diagnosis and treatment of these rare diseases.

HYPERTENSION AND RENAL CELL CARCINOMA

Advances in tumour diagnosis and treatment, particularly targeted drugs, have considerably improved renal cell carcinoma (RCC) survival while increasing the incidence of hypertension (HTN). As a result, identifying risk factors and enhancing therapeutic treatment for RCC and HTN patients are critical challenges. This study looked at both preclinical and clinical risk factors for HTN-RCC comorbidity. Obesity, smoking, and other lifestyle choices may be risk factors for both RCC and HTN. Second, RCC and HTN medications can interact with one another. Then, HTN treatment and RCC comorbidity reduction were addressed. Additionally discussed current study flaws and potential directions Finally, the goal of this study is to expand cardio-oncology knowledge and to help patients who are at high risk of or suffering from RCC and HTN.

Incidental Diagnosis and Treatment of Renal Cell Carcinoma in a Kidney Pre-Transplant Recipient

Introduction:Renal cell carcinoma (RCC) accounts for 80–90% of all kidney cancers with peak age incidence between 60–70 years. The three commonest symptoms are haematuria, flank pain and flank mass. The best treatment option for chronic kidney disease is renal transplantation. Chronic kidney disease is one of the risk factors for RCC. Most cases are diagnosed after renal transplantation; diagnosis during work up for renal transplantation in an asymptomatic patient is rare, especially in environment where patients hardly receive cure for kidney cancer because most cases are diagnosed late, at the advanced stage of the disease. Case Presentation: A 62-year-old male on management for chronic kidney disease who was diagnosed with right renal tumour during work up for renal transplantation. He had right radical nephrectomy with histology report revealing localized RCC (clear cell variant). He is currently on observation for 2 years before transplantation. Conclusion: Diagnosis of RCC in an asymptomatic patient during work up for renal transplantation is rare. The prognosis of this disease is improved significantly if diagnosed and treated before renal transplantation.

The Incidence of Renal Cell Carcinoma Is Increased in Patients With Obstructive Sleep Apnea

Background and Objective Many studies have indicated that obstructive sleep apnea (OSA) is linked to the development of cancer. However, there have been few studies about the link between OSA and renal cell carcinoma (RCC). This study investigated the relationship between OSA and RCC by analyzing the data from the Korea National Health Insurance Service.Methods 198574 patients (≥ 20 years of age) newly diagnosed with OSA from 2007 to 2014 were included and 992870 control groups were selected through propensity score matching according to sex and age. The average follow-up period was 4.6 years. The primary outcome was newly diagnosed RCC. The hazard ratio for RCC in patients with OSA was compared to that in the control group.Results The incidence of RCC was significantly higher among patients with OSA than among controls (hazard ratio, 1.65; 95% confidence interval, 1.41–1.93).Conclusions OSA may be a potential risk factor for RCC.

Epidemiology and Prevention of Renal Cell Carcinoma.

Simple SummaryThe incidence of renal cell carcinoma (RCC) rises globally with the highest rates in developed countries. This indicates not only the impact of advanced imaging, but also an increased prevalence of modifiable risk factors such as smoking, obesity, and hypertension. This review will summarize the epidemiology and genetic variation of RCC, primary prevention-involving risk factors, and secondary prevention through early detection with a focus on biomarkers.With 400,000 diagnosed and 180,000 deaths in 2020, renal cell carcinoma (RCC) accounts for 2.4% of all cancer diagnoses worldwide. The highest disease burden developed countries, primarily in Europe and North America. Incidence is projected to increase in the future as more countries shift to Western lifestyles. Risk factors for RCC include fixed factors such as gender, age, and hereditary diseases, as well as intervening factors such as smoking, obesity, hypertension, diabetes, diet and alcohol, and occupational exposure. Intervening factors in primary prevention, understanding of congenital risk factors and the establishment of early diagnostic tools are important for RCC. This review will discuss RCC epidemiology, risk factors, and biomarkers involved in reducing incidence and improving survival.

Family History of Cancers Increases Risk of Renal Cell Carcinoma in a Chinese Population.

PurposeTo explore the impact of family history (FH) on renal cell carcinoma (RCC) and its pathological subtype clear cell RCC (ccRCC) in a Chinese population; a significant association has previously been determined not only in familial cancer syndrome but also in sporadic cases in western populations.MethodsConsecutive patients with kidney tumors from October 2017 to May 2021 at a tertiary hospital in Shanghai were enrolled in the study. Demographic and clinical information was collected, including age, gender, FH (positive or negative, types of cancers, degree of relatives, etc.), pathological diagnosis, and Fuhrman grades.ResultsA positive FH of any cancer was observed in 26.5% of the RCC patients, while only 16.8% patients with benign kidney tumor were found to have a positive FH. A strong correlation was observed between FH of any cancers in first-degree relatives and RCC (odds ratio [OR]=4.60, 95% confidence interval [CI]: 1.95–10.85, P=5.50×10−5) or ccRCC (OR=4.63, 95% CI: 1.95–11.02, P=9.63×10−5). In subgroup analysis, FH of digestive cancers was significantly associated with RCC (OR=4.42, 95% CI: 1.35–14.51, P=0.005) or ccRCC (OR=4.14, 95% CI: 1.25–13.75, P=6.84×10−4). Similar results were found in multivariate analyses. However, no significant association was observed between FH and age at onset.ConclusionFH was an independent risk factor for RCC and ccRCC in this Chinese population. FH of any cancer in first-degree relatives and FH of digestive cancers were found to be the most significant risk factors for kidney cancers.

Obesity in Relation to Renal Cell Carcinoma Incidence and Survival in Three Prospective Studies

To disentangle the “obesity paradox” in renal cell carcinoma (RCC), we examined associations of body mass index (BMI) and weight change with RCC risk and survival in the Health Professionals Follow-up Study (HPFS) and Nurses’ Health Study (NHS) 1 and 2. We estimated cohort-specific and summary covariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for RCC incidence, as well as RCC-specific survival among cases in the pooled HPFS and NHS data. Cumulative average BMI was associated with a higher risk of total RCC (summary HR 2.16, 95% CI 1.77–2.63 for BMI ≥30 vs 18–<25 kg/m2; p trend <0.001) and fatal RCC (HR 2.03, 95% CI 1.37–3.01; p trend <0.001). Prediagnosis BMI was not associated with RCC death. However, first postdiagnosis BMI (HR 0.51, 95% CI 0.29–0.89; p trend 0.006) and prediagnosis to postdiagnosis weight change (HR 0.52, 95% CI 0.29–0.91; p trend 0.001) were significantly inversely associated with RCC death. These results support obesity as a risk factor for total and fatal RCC. They undermine the obesity paradox by suggesting that weight loss around diagnosis, and not low BMI itself, is associated with worse prognosis. Patient summaryWe studied obesity in kidney cancer and found that obesity is associated with getting and dying from the disease. Body mass index at diagnosis is not an ideal factor for predicting prognosis, as patients who have lost weight are likely to have more aggressive cancer.

Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Previous studies have suggested that components of one‐carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case‐control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5′‐phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these associations were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared to high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development.

INCIDENTAL SOLE CONTRALATERAL PLEURAL METASTASIS FROM RENAL CELL CARCINOMA SEVEN YEARS POST NEPHRECTOMY

TOPIC: Disorders of the Pleura TYPE: Medical Student/Resident Case Reports INTRODUCTION: Renal cell carcinoma (RCC) accounts for 3% of all adult male cancers, and half of them are incidental findings on imaging [1]. 18% of patients have synchronous metastasis at RCC diagnosis, and 85% have metachronous metastasis within five years after surgery. A better prognosis is seen with a metachronous metastasis occurring after a long disease-free interval [2] CASE PRESENTATION: A 68-year-old male presented to an outside emergency department with generalized weakness, fatigue, and loss of appetite for a week's duration with no respiratory complaints. He was a former smoker who quit 40 years back. He had significant asbestos exposure as a sandblaster and changing railroad brake shoes. His initial blood work revealed an acute kidney injury with a serum creatinine of 14.8 mg/dL with no leukocytosis. Computed tomography (CT) abdomen revealed an obstructive right ureteropelvic junction stone (1.4 x 1 cm) with moderate hydronephrosis. Chest x-ray and CT revealed multiple right pleural soft tissue masses (largest measuring 7.7 x 3.1 x 3.5 cm) with no effusion concerning for malignancy (Figure A). Past medical history was significant for left clear cell RCC grade 3/4 with no invasion (T1bNxMx) treated by left radical nephrectomy seven years ago. His obstruction was relieved by urological intervention. A nuclear positron emission tomography showed hypermetabolic right pleural masses and a right paratracheal lymph node (Figure B). A CT-guided biopsy returned positive for metastatic RCC (Figure C1-C2). His creatinine improved, and he was discharged with an oncology follow-up DISCUSSION: The risk of RCC metastasis via hematogenous or lymphatic spread increases if it is locally advanced (stage 3-4), higher nuclear grade, and clear cell histology [2]. The lung is the frequent site of metastasis (45%), and pleural lesions occur in 12% along with lung spread [3]. Isolated pleural spread without an effusion is rare. Dormant metastasis uses Batson's venous plexus draining into thoracic veins (bronchial and intercostal) and reaches the pleura rather than by lung parenchyma direct extension [2]. Most reported cases of solitary pleural spread are symptomatic with effusion. Our patient was asymptomatic with incidental contralateral pleural metastasis without pleural effusion seven years postresection with a rare combination of pleural and paratracheal lymph node spread. 5-15% of patients recur with a distant spread questioning the current five-year surveillance strategy [4] CONCLUSIONS: Metastatic RCC to the pleura is a rare finding. This diagnosis should be considered in patients with RCC history, even if the presentation is many years after initial diagnosis and treatment. Postnephrectomy, the surveillance should be based on an individual's RCC risk factors REFERENCE #1: Ohnishi H, Abe M, Hamada H, et al. Metastatic renal cell carcinoma presenting as multiple pleural tumours. Respirology. 2005;10(1):128-31 REFERENCE #2: Brufau BP, Cerqueda CS, Villalba LB, Izquierdo RS, González BM, Molina CN. Metastatic renal cell carcinoma: radiologic findings and assessment of response to targeted antiangiogenic therapy by using multidetector CT. Radiographics. 2013;33(6):1691-716 REFERENCE #3: Saitoh H. Distant metastasis of renal adenocarcinoma. Cancer. 1981;48(6):1487-91 DISCLOSURES: No relevant relationships by Mohammed Alnijoumi, source=Web Response No relevant relationships by Cliff Chen, source=Web Response No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response

Redox-sensitive signaling pathways in renal cell carcinoma.

Renal cell carcinoma (RCC) is one of the most lethal urological cancers, highly resistant to chemo and radiotherapy. Obesity and smoking are the best-known risk factors of RCC, both related to oxidative stress presence, suggesting a significant role in RCC development and maintenance. Surgical resection is the treatment of choice for localized RCC; however, this neoplasia is hardly diagnosable at its initial stages, occurring commonly in late phases and even when metastasis is already present. Systemic therapies are the option against RCC in these more advanced stages, such as cytokine therapy or a combination of tyrosine kinase inhibitors with immunotherapies; nevertheless, these strategies are still insufficient. A field poorly analyzed in this neoplasia is the status of cell signaling pathways sensible to the redox state, which have been associated with the development and maintenance of RCC. This review focuses on alterations reported in the following redox-sensitive molecules and signaling pathways in RCC: mitogen-activated protein kinases, protein kinase B (AKT)/tuberous sclerosis complex 2/mammalian target of rapamycin C1, AKT/glycogen synthase kinase 3/β-catenin, nuclear factor κB/inhibitor of κB/epidermal growth factor receptor, and protein kinase Cζ/cut-like homeodomain protein/factor inhibiting hypoxia-inducible factor (HIF)/HIF as potential targets for redox therapy.

985Sex differences in the incidence of renal cell carcinoma: results from the EPIC cohort study

Abstract Background Incidence of renal cell carcinoma (RCC) is two-fold higher in men compared with women. This ratio has been remarkably stable, both geographically and over time. We investigated whether established risk factors for RCC can explain the higher incidence in men. Methods 230,399 participants in the EPIC cohort study with complete data for BMI, history of hypertension, and smoking variables were included. Cox regression models with age as the time-scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for sex. Results We identified 690 incident RCC cases. The marginal HR [95% CI] for men versus women was 2.30 [1.98, 2.69]. There was no strong evidence for interactions between hypertension, BMI, or smoking status and sex. Adjusting for BMI, hypertension and smoking variables did not materially affect the estimate (HR: 2.18 [1.85, 2.56]), accounting for only 10% of the observed excess risk. In contrast, smoking factors alone could account for 88% of the observed excess risk of lung cancer for men (marginal HR: 2.19 [2.02, 2.38]; adjusted HR: 1.14 [1.04, 1.25]) Conclusions The two-fold higher incidence of RCC in men compared with women cannot be explained by established risk factors. Key messages Whilst obesity, hypertension, and smoking are established risk factors for RCC, they cannot account for the greater incidence among men compared with women. This indicates the presence of as yet unknown factors to which men are more susceptible than women.

Racial Diversity Among Histology of Renal Cell Carcinoma at an Urban Medical Center

Non-Hispanic blacks (NHB) with renal cell carcinoma (RCC) are more likely to have papillary RCC (pRCC) than non-Hispanic whites (NHW). Data on histologic subtypes in RCC in Hispanics (H) are also sparse. Previous studies have shown that pRCC is more prevalent in NHB than in NHW, but they analyzed predominantly NHW populations. The Montefiore-Einstein Center for Cancer Care (MECC) serves a predominantly NHB and H population in the Bronx, NY. We investigated histologic subtype specific associations with established RCC risk factors in this population. The MECC tumor registry was used to identify patients≥ 18 years of age treated with partial or radical nephrectomy between January 2000 and December 2015. An institutional software program and individual chart review were used to obtain demographic data (including self-reported race, age, and sex), pathology data, and RCC risk factors (hypertension, diabetes, renal function, weight). Data were modeled by multinomial logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 1010 RCC cases were identified. Of these, 232 (23.0%) occurred in NHW, 383 (37.9%) NHB, 181 (17.9%) H, and 214 (21.2%) other. A total of 530 cases (52.5%) were clear cell (ccRCC) histology, 257 (25.4%) pRCC, 100 (9.9%) chromophobe (cRCC), and 123 (12.2%) other. Individuals with pRCC compared to ccRCC were more likely to be NHB than NHW (OR, 4.41; 95% CI, 2.81-6.93) but were less likely to be female (OR, 0.50; 95% CI, 0.35-0.72). Individuals with pRCC were also less likely to be H than NHW (OR, 0.52; 95% CI, 0.27-0.99). Patients with cRCC were also more likely to be NHB than NHW (OR, 2.23; 95% CI, 1.06-4.67). In the MECC data set, histology of RCC varies by race, confirming earlier reports that non-ccRCC is more common in NHB than NHW. We also report that pRCC is less common in H than NHW.

Association of Processed Meats and Alcohol Consumption with Renal Cell Carcinoma: A Worldwide Population-Based Study

The link between diet and renal cell carcinoma (RCC) is still unclear. The purpose of this study was to evaluate the association of diet with RCC’s incidence and mortality rates worldwide. We conducted an ecological study including 170 countries, whose data on age-standardized (AS) incidence and mortality rates of RCC, dietary factors, and potentially confounding factors such as obesity, insufficient physical activity, tobacco smoking, hypertension, diabetes, and human development index (HDI) were collected and available on May 2020 from the Global Cancer Observatory, the Global Dietary Database, the Global Health Observatory data repository, the Diabetes Atlas 9th edition and the Human Development Report 2019. Univariable and multivariable linear regression analyses were performed to determine the association of dietary factors with incidence and mortality rates of RCC adjusted for the effects of population age and potentially confounding factors. Intake of processed meats and consumption of alcohol were both positively associated with AS incidence rates of RCC (β = 0.11, P < 0.001 and β = 0.1, P = 0.044, respectively). We suggest that high consumption of processed meats and/or alcohol is a risk factor for RCC. However, they were not associated with mortality. Further research is needed at an individual level. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2020.1856388.