Sex‐specific analysis of renal cell carcinoma histology and survival in Japan: A population‐based study 2004 to 2016

Abstract

Background and aims In Western countries, sex differences in renal cell carcinoma (RCC) histology and survival have been previously described: compared with men, clear cell subtype is more common but overall prognosis is better among women. The goal of the present study was to examine sex differences in RCC histology and survival in Japan, using a large‐scale population‐based data set. Methods With the use of a population‐based cancer registry in Japan (2004‐2016), patients with primary RCC were followed for 5 years (median follow‐up time 2.1 years). We distinguished histological subtypes of clear cell, papillary, and chromophobe from “others” subtype. Sex‐specific prevalence ratio (PR) for each histological subtype was estimated by Poisson regression with robust variance, adjusted for age and year of diagnosis. Sex‐specific survival rates were estimated by Cox proportional hazard regression, adjusted for age, year of diagnosis, histological subtypes, and other prognostic variables, with multiple imputation. Results The prevalence of clear cell and “others” subtypes was similar between men and women among all the 5265 study subjects during the 12 years of study (clear cell, male 88.6% vs female 87.1%; “others“, male 5.3% vs female 5.3%). However, papillary subtype was less common among women than men (male 4.6% vs female 2.8%; PR = 0.63; 95% CI, 0.45‐0.88), while chromophobe subtype was more common among women (male 1.6% vs female 4.8%; PR = 3.18; 95% CI, 2.26‐4.47). Although “others” subtype (but not papillary/chromophobe subtypes) independently predicted prognosis (HR = 1.74; 95% CI, 1.32‐2.30), no sex differences were observed in RCC survival. Conclusion We did not observe a statistically significant difference in the prevalence of clear cell subtype between men and women in Japan, which differs from the pattern previously described in Western countries. Sex differences in RCC histology may not affect RCC survival in this population.

Gene Expression and Co-expression Networks Are Strongly Altered Through Stages in Clear Cell Renal Carcinoma

“…In the case of Figure 6 , the fact that chromosome Y is the only one with a higher cis- rate in control network than in ccRC stages may imply that, for this chromosome and its genes, local co-expression is crucial to maintain a proper functionality. It is widely known that two thirds of all ccRC cases correspond to men (Aron et al, 2008 ; Woldrich et al, 2008 ; Qu et al, 2015 ; Zaitsu et al, 2020 ). Since Chr Y is directly linked to gender, one may argue that an imbalance in the cis-/trans- proportion may be implicated in gender-bias on clear cell renal carcinoma.…”

Gender-Related Approach to Kidney Cancer Management: Moving Forward

“…Compared with ccRCC cases, patients with pRCC were significantly less likely to be female (odds ratio (OR): 0.60; 95% confidence interval (CI): 0.43-0.83), while patients with chRCC were significantly more likely to be female (OR: 2.32; 95% CI: 1.44-3.74). Despite the lower number of RCCs in Asia, a recent Japanese retrospective study [14] on 5265 patients with RCC (72.6% male, 27.4% female) confirmed the different distribution of histological subtypes between men and women. While the prevalence of ccRCC/"others" subtypes was similar between genders, pRCC was more prevalent among men, as compared to women (4.6% vs. 2.8%; p = 0.004), and chRCC was less prevalent among men, as compared to women (1.6% vs. 4.8%; p < 0.001).…”

“…Not all studies present a higher cancer-specific survival and overall survival in women rather than in men. Specifically, Zaitsu et al [14] analyzed a cohort of 5265 patients with RCC and equally distributed grades and stages (high grade:~10%, p = 0.85; late stage:~26%, p = 0.40). In the survival analysis, the five-year OS rate was 72% for both males and females, without statistically significant differences between genders, even after stratifying by histological subtypes.…”

Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence

“…This difference may be clinically important, as it might partially explain the more favorable outcomes of RCC among females (considering the less aggressive behavior of chromophobe RCC) [12,105,116]. A recent Japanese retrospective study confirmed these findings [127]. Similarly, the sex-stratified analysis by Bhindi et al, found that the percentages of both malignant histology as well as aggressive histology were consistently higher for males [115].…”