Smoking Not a Risk Factor for All RCC Subtypes

Bladder Cancer Prognosis Unaffected by Smoking Status
Bladder Cancer Prognosis Unaffected by Smoking Status

Tobacco smoking is a well recognized modifiable risk factor for renal cell carcinoma (RCC), but not for all RCC histologic subtypes, according to researchers. 

In a study of 816 patients undergoing nephrectomy, a team led by Eric C. Kauffman, MD, of the Roswell Park Cancer Institute in Buffalo, discovered that smoking is a risk factor for clear cell and papillary RCC (ccRCC and pRCC, respectively), but not chromophobe RCC (chRCC). Using propensity analyses adjusting for multiple variables, active smoking was independently associated with a significant 2.2 and 2.4-fold increased odds of ccRCC and pRCC, respectively, Dr. Kauffman's group reported in The Journal of Urology (2015;194:640-646). 

According the investigators, their study provides the first demonstration that smoking, the most important modifiable risk factor for RCC, increases the risk of certain common RCC subtypes but not others. “These findings underscore the distinct carcinogenic mechanisms underlying RCC subtypes, including a differential effect of tobacco carcinogens,” they concluded. “Important in this regard may be tobacco induced oxidative stress injury to the renal proximal tubule, the presumed origin of ccRCC and pRCC but not chRCC.” 

Dr. Kauffman and his colleagues said the new findings may be clinically useful in predicting renal tumor histologic subtype. Given the lower metastatic potential of chRCC compared with pRCC and ccRCC, knowledge of the histologic subtype “can aid in clinical risk stratification, including among older or sicker patients with early stage renal tumors who are debating surgical resection vs active surveillance.” 

The authors noted that the mechanisms by which tobacco might promote development of RCC are unclear. “Oxidative stress injury with smoking mediated by increases in local hypoxia and reactive oxygen species could explain the risk of ccRCC and pRCC and not chRCC,” they wrote. 

They pointed out that the association of smoking with angiogenesis might also contribute to ccRCC tumorigenesis. “Nicotine is known to increase endothelial cell number, capillary network formation, and angiogenic response in neoplasia, mediated in part by the vascular endothelial growth factor protein commonly up-regulated in ccRCC.” 

Dr. Kauffman's team acknowledged study limitations, including the retrospective study design and restriction to a single institution and geographic region. Additionally, they noted, smoking may be associated with confounding variables that affect RCC risk but were not measured, including a history of hypertension. 

Of the 816 patients in the study, 705 had nonfamilial RCC and 111 had benign pathology and 51% reported smoking (21% active smokers and 30% former smokers). 

The new study adds to a growing number of recent investigations characterizing the different RCC histologic subtypes and their associated risk factors. For example, researchers at Vanderbilt University Medical Center in Nashville, Tenn., studied RCC tumors from 1,532 patients who underwent nephrectomy and found a substantially higher proportion of patients with pRCC among black patients than white patients, according to a paper published online ahead of print in BJU International. Additionally, patients with chRCC were significantly more likely to be female. In a separate study of 487 RCC patients, also published in BJU International (2014;114:496- 502), researchers demonstrated that increased visceral fat was associated with ccRCC, and visceral fat area outweighed the effects of body mass index (BMI) and type 2 diabetes for predicting RCC pathology in multivariate analyses.

Additionally, a South Korean study of 2,769 patients with non-metastatic RCC demonstrated that higher BMI was associated with greater recurrence-free survival (RFS) and cancer-specific survival (CSS) rates among patients with ccRCC and lower RFS and CSS rates among those with chRCC, according to a findings published in Clinical Genitourinary Cancer (2015;13:461-468). The study found no association between BMI and RFS or CSS in patients with pRCC.

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