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Is physical activity related to renal cell carcinoma? A systematic review

1Department of Epidemiology, Student Research Committee, School of Public Health, Iran University of Medical science, Tehran, Iran 2Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 3Department of Obstetrics and Gynecology, Iran University of Medical Sciences, Tehran, Iran 4Department of Pathology and Laboratory Medicine, Iran University of Medical Sciences, Firoozgar Hospital, Tehran, Iran


Introduction
Ninety percent of all cancers related to kidney is renal cell carcinoma (RCC), and it was increasing in recent years worldwide (1). Hypertension, cigarette and obesity are some important modifiable risk factors for developing RCC (2). According to the studies, regular physical activity may prevent RCC by losing weight and treating hypertension, since, there is a negative relationship between physical activity and RCC (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). There are some researches without unanimous results regarding the relationship between physical activity and developing RCC (5,14). A potential way to reduce developing RCC and its consequences can be influenced by the modification of lifestyle factors such as diet, exercise and smoking (15). The risk of RCC depends on ethnicity while, black Americans develop more than white Americans (2,16). Considering that the certain relationship between RCC and physical activity is controversial and crucial, this study reviewed the relationship between renal cell carcinoma and physical activity.

Selection of articles
The references of articles were imported to Endnote. The duplicates were removed. Using the title of selected articles, irrelevant studies assessed by two independent investigators were removed. The selected articles carried out on humans and published in English.

Data extraction
Information dealing with the studies were the author's name, year, design of the study, participants number and the conclusion of each article, in such a way that were extracted by two independent investigators. The differences in the extraction were solved by a third independent investigator.

Results
There were 37 742 subjects participated in the selected articles for systematic review of 11 published papers including five standard case-control, three cohorts and three population-based case-control design (Table 1). Figure 1 shows the steps of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Discussion
The first study by Chiu et al in 2006 was conducted in the United States about the relationship between obesity with risk of RCC and the moderating effect of physical activity. This research was a population-based case-control study that was performed on 406 patients and 2434 controls. Non-occupational physical activity had an inverse relationship with the risk of RCC among women (OR = 2.5; 95% CI = 1.2-5.2) while there was a moderating effect of physical activity with body mass index on the RCC (3). The second study by Pan et al was conducted in 2006. The report was a population-based case-control study aimed to study the effects of energy intake, overweight, and low physical activity on the risk of RCC and nonrenal cell cancer in Canada during 1994-1997. In this study, 810 cases and 3160 controls were investigated. The role of recreational physical activity needs to be further investigated (4). Tavani et al in 2007 conducted a study to investigate the relationship between RCC and suitable physical activity in Italy. In this case-control study, 767 cases with 1534 controls from 1992 to 2004 were studied. The results showed that, compared with the lowest level of occupational physical activity, the ratio of the risk of RCC for the highest activity level at age 12 was 0.65 (95% CI: 0.49-0.87), for 15-19 years, 0.67 (95% CI: 0.53-0.84 ) for 30-39 years was 0.74 (95% CI: 0.59-0.93) and for 50-59 years it was 0.71 (95% CI: 0.55-0.92). Additionally, no significant relationship was found between leisure time physical activities (5). The fourth study by George et al, in 2011 was done to assess the effect of long-term sitting on the risk of RCC on elderly persons. The study was a cohort and conducted from 1996 to 2006. There was no relationship between long-term sitting and risk of RCC in both men and women (HR = 1.11, 95% CI: 0.87, 1.41) (6).
Shu et al conducted a study regarding the balance of energy, polymorphism in the mammalian target of rapamycin (mTOR) pathway, and the risk of RCC. In this case-control study, 577 non-Hispanic white cases versus 593 healthy controls were studied. The results of the study showed that low physical activity is highly linked with an increase of cancer by 4.08 times (7). In the study of Sormunen et al, the relationship between suitable physical activity and the risk of cancer was investigated in Finnish athletic males in a cohort study. In this cohort, 2448 athletes and 1712 referents were followed up for cancer during 1986-2010. The results showed that the standardized incidence ratio among athletes for kidney cancer was 0.23 (95% CI: 0.06-0.57). The study concluded that athlete males were clearly less likely to have cancer than nonathletic males (8). Likewise, in the study of Williams et al, the reduced risk of kidney cancer due to walking and running was studied. In this study, the data of National Runners' Health Study cohort was reviewed for 54,956 people. The results of the study showed that walking and running can reduce the incidence of kidney cancer independently of other risk factors (9).
Accordingly, Xiao et al reviewed the relationship between physical activity and RCC among whites and blacks in the United States. In this population-based case-control study, frequency matching was performed for 1217 cases and 1235 controls by age, gender, and race. The results of the study showed that physical activity may be has a reverse relationship with RCC risk in white women, but in this study, no such relationship was found for blacks (10). Another study by Melkonian et al was conducted to evaluate the number of mitochondrial DNA copies in peripheral blood leukocytes and the risk of clear cell RCC (ccRCC). In this case-control study, 608 cases and 629 controls were matched based on age and gender frequency for the relationship between mitochondrial DNA copy number (mtDNAcn) and the risk of ccRCC. The results of this study showed that mtDNAcn is associated with a high risk of ccRCC in young people, women, nonsmoking people, those with low activity, and people without a history of hypertension (11).
Cannioto et al conducted a study on the relationship between physical inactivity and the risk of RCC in 2017. In this hospital-based case-control study, 160 patients with kidney cancer and 208 patients with bladder cancer were evaluated. Patients were matched based on age with 766 frequency-matched controls. They found a direct relationship between RCC with lifetime recreational physical inactivity (12). Peters et al in Canada conducted a study, using the National Enhanced Cancer Surveillance System (NECSS) data in 2018. In this study, 727 cases of kidney cancer (83% of RCCs) and 2547 controls were analyzed. Physical activity has a negative relationship with kidney cancer (13).

Conclusion
According to the results, physical inactivity has a positive relationship with RCC. On the other hand, physical activity has a reverse relationship with RCC. It is essential to do an exercise program for those who are on the risk of RCC such as those who live in the family with familial aggregation of cancer especially kidney cancer.

Authors' contribution
Study concept and design: NM, BH and RV. Search strategy: BH and RV. Extraction of data: NM, PH, GD and BB. Interpretation of data: RV, BB and GD. Draft of the manuscript: RV and NM. Final revision: BH and BB. Study supervision: BH and NM.

Conflicts of interest
There is no conflict of interest in this review study.

Ethical considerations
Ethical issues (including plagiarism, data fabrication, double publication) have been completely observed by the authors.

Funding/Support
None.