Differences in risk factors for molecular subtypes of clear cell renal cell carcinoma Journal Article
| Authors: | Purdue, M. P.; Rhee, J.; Moore, L.; Gao, X.; Sun, X.; Kirk, E.; Bencko, V.; Janout, V.; Mates, D.; Zaridze, D.; Petruzella, S.; Hakimi, A. A.; Linehan, W. M.; Chanock, S. J.; Brennan, P.; Furberg, H.; Troester, M.; Rothman, N. |
| Article Title: | Differences in risk factors for molecular subtypes of clear cell renal cell carcinoma |
| Abstract: | The ccA and ccB molecular subtypes of clear cell renal cell carcinoma (ccRCC) have well-characterized prognostic relevance. However, it is not known whether they possess distinct etiologies. We investigated the relationships between these subtypes and RCC risk factors within a case-control study conducted in Eastern Europe. We analyzed risk factor data for ccA (n = 144) and ccB (n = 106) cases and 1476 controls through case-only and case-control comparisons to assess risk factor differences across subtypes using logistic and polytomous regression models. We also performed a meta-analysis summarizing case-only results from our study and three patient cohorts. Patients with ccB tumors had poorer survival than those with ccA tumors and were more likely to be male (case-only odds ratio [OR] 2.68, 95% confidence interval [CI] 1.43-5.03). In case-control analyses, body mass index was significantly associated with ccA tumors (OR 2.45, 95% CI 1.18-5.10 for ≥35 vs <25 kg/m2) but not with ccB tumors (1.52, 0.56-4.12), while trichloroethylene was associated with ccB but not ccA (OR 3.09, 95% CI 1.11-8.65 and 1.25, 0.36-4.39 respectively for ≥1.58 ppm-years vs unexposed). A polygenic risk score of genetic variants identified from genome-wide association studies was associated with both ccA and, in particular, ccB (OR 1.82, 1.11-2.99 and 2.87, 95% CI 1.64-5.01 respectively for 90th vs 10th percentile). In a meta-analysis of case-only results including three patient cohorts, we still observed the ccB excess for male sex and the ccA excess for obesity. In conclusion, our findings suggest the existence of etiologic heterogeneity across ccRCC molecular subtypes for several risk factors. © 2021 Union for International Cancer Control. This article has been contributed to by US Government employees and their work is in the public domain in the USA. |
| Keywords: | adult; cancer survival; controlled study; aged; middle aged; major clinical study; overall survival; case control study; cancer staging; cancer grading; disease association; cohort analysis; genetic association; genetic variability; genome-wide association study; risk factors; obesity; risk factor; cancer mortality; risk assessment; body mass; disease severity; sex difference; epidemiology; clear cell renal cell carcinoma; molecular pathology; case-control study; human; male; female; article; trichloroethylene; clear cell renal cell carcinoma molecular subtype; clear cell renal cell carcinoma molecular subtype cca; clear cell renal cell carcinoma molecular subtype ccb |
| Journal Title: | International Journal of Cancer |
| Volume: | 149 |
| Issue: | 7 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2021-10-01 |
| Start Page: | 1448 |
| End Page: | 1454 |
| Language: | English |
| DOI: | 10.1002/ijc.33701 |
| PUBMED: | 34058014 |
| PROVIDER: | scopus |
| PMCID: | PMC8628648 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2021 -- Source: Scopus |
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