Kidney Carcinoma – Key Facts About the Disease With the Highest Incidence Worldwide in the Czech Republic
The incidence of renal carcinoma is increasing every year. About a quarter of the cases are still diagnosed in the metastatic stage, yet early treatment can save lives. Below, we briefly summarize data on the incidence, etiology, and risk factors of this malignant disease based on a literature review from 1945–2015. These findings may be significant for prevention and screening in high-risk individuals.
Introduction
Kidney carcinoma is the 12th most common cancer worldwide. It accounts for 3% of all malignancies diagnosed in adults. It occurs more frequently in men and in developed countries, namely Europe, North America, and Australia. The highest incidence is in the Czech Republic (24.1/100,000 population in men and 10.5/100,000 in women in 2012).
Renal cell carcinoma (RCC) accounts for 80–85% of all kidney malignancies. The most common histological type is clear cell carcinoma (75% of RCC cases), formerly known as Grawitz's tumor. Other types of RCC include papillary (10%), chromophobe (5%), and collecting duct carcinoma (medullary, < 1%), which is highly aggressive. Wilms' tumor (nephroblastoma), typical in children, accounts for only 1% of all kidney malignancies.
Clinical Symptoms
In the literature, “typical” symptoms of renal carcinoma are often described, including micro- or macroscopic hematuria, lumbar pain, and a palpable abdominal mass. However, these are observed in < 10% of patients. Due to the retroperitoneal location of the kidney, the disease can remain asymptomatic for a long time. Paraneoplastic symptoms such as hypercalcemia, hypertension, polycythemia, amyloidosis, liver function disorder (Stauffer’s syndrome), fever, or weight loss may also indicate the disease.
Renal carcinoma is often diagnosed (> 60% of cases) as an incidental finding, for example, during an ultrasound examination of the abdomen. In 20–30% of cases, the disease is detected at a metastatic stage. In such cases, the median survival is 13 months, and the 5-year survival rate is < 10% despite advances in medicine.
Risk Factors
Risk factors for renal carcinoma include smoking, obesity, insufficient physical activity, exposure to nephrotoxic substances, medications (phenacetin analgesic), radioactive radiation, and comorbidities such as hypertension, diabetes mellitus, or dyslipidemia. In observational studies, up to half of renal carcinomas were associated with obesity (with a BMI > 30 kg/m2), with the risk increasing by 20–30% for every 5 kg/m2.
The etiology of RCC also involves circulating vitamin D-binding protein levels, vitamin D3, and polymorphisms of the vitamin D receptor. Cytochrome P450 polymorphisms, especially related to the CYP1A1 isoenzyme, which plays a crucial role in the metabolism of carcinogenic polycyclic aromatic hydrocarbons, also play a role. Nutritional factors such as ochratoxins and citrinin are significant. These mycotoxins, used in agriculture, can contaminate food and accumulate in the human body, where they exert nephrotoxic, hepatotoxic, and immunological effects.
Another significant risk factor is genetic predisposition. Clear cell carcinoma is associated with a mutation in the VHL gene (von Hippel-Lindau). Papillary carcinoma can be caused by a mutation in the MET gene or hereditary leiomyomatosis (mutation of the fumarate hydratase gene), while chromophobe carcinoma can result from a mutation of the tumor suppressor gene for folliculin (Birt-Hogg-Dubé syndrome).
We distinguish between hereditary and sporadic forms of RCC. Hereditary forms are more often multifocal, bilateral, and diagnosed at a younger age. Extrarenal neoplasms (such as uterine tumors, pancreatic cysts, adrenal pheochromocytoma, etc.) are also more common.
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Source: Petejová N., Martínek A. Renal cell carcinoma: review of etiology, patophysiology and risk factors. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016; 160 (2): 183–194, doi: 10.5507/bp.2015.050.
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