Clinical and genetic risk factors for adverse metabolic outcomes in North American testicular cancer survivors Journal Article


Authors: Zaid, M. A.; Gathirua-Mwangi, W. G.; Fung, C.; Monahan, P. O.; El-Charif, O.; Williams, A. M.; Feldman, D. R.; Hamilton, R. J.; Vaughn, D. J.; Beard, C. J.; Cook, R.; Althouse, S. K.; Ardeshir-Rouhani-Fard, S.; Dinh, P. C. Jr; Sesso, H. D.; Einhorn, L. H.; Fossa, S. D.; Travis, L. B.; for the Platinum Study Group
Article Title: Clinical and genetic risk factors for adverse metabolic outcomes in North American testicular cancer survivors
Abstract: Background: Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. Patients and Methods: TCS were aged <55 years at diagnosis and received first-line chemotherapy. Patients underwent physical examination, and had lipid panels, testosterone, and soluble cell adhesion molecule-1 (sICAM-1) evaluated. A single nucleotide polymorphism in rs523349 (5-?-reductase gene, SRD5A2), recently implicated in MetS risk, was genotyped. Using standard criteria, MetS was defined as ?3 of the following: hypertension, abdominal obesity, hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol level, and diabetes. Matched controls were derived from the National Health and Nutrition Examination Survey. Results: We evaluated 486 TCS (median age, 38.1 years). TCS had a higher prevalence of hypertension versus controls (43.2% vs 30.7%; P<.001) but were less likely to have decreased HDL levels (23.7% vs 34.8%; P<.001) or abdominal obesity (28.2% vs 40.1%; P<.001). Overall MetS frequency was similar in TCS and controls (21.0% vs 22.4%; P=.59), did not differ by treatment (P=.20), and was not related to rs523349 (P=.61). For other CVD risk factors, TCS were significantly more likely to have elevated low-density lipoprotein (LDL) cholesterol levels (17.7% vs 9.3%; P<.001), total cholesterol levels (26.3% vs 11.1%; P<.001), and body mass index ?25 kg/m2 (75.1% vs 69.1%; P=.04). On multivariate analysis, age at evaluation (P<.001), testosterone level ?3.0 ng/mL (odds ratio [OR], 2.06; P=.005), and elevated sICAM-1 level (ORhighest vs lowestquartile, 3.58; P=.001) were significantly associated with MetS. Conclusions and Recommendations: Metabolic abnormalities in TCS are characterized by hypertension and increased LDL and total cholesterol levels but lower rates of decreased HDL levels and abdominal obesity, signifying possible shifts in fat distribution and fat metabolism. These changes are accompanied by hypogonadism and inflammation. TCS have a high prevalence of CVD risk factors that may not be entirely captured by standard MetS criteria. Cancer treatment–associated MetS requires further characterization. © JNCCN—Journal of the National Comprehensive Cancer Network
Keywords: adult; cancer chemotherapy; controlled study; aged; major clinical study; single nucleotide polymorphism; hypertension; cancer patient; comparative study; disease association; prevalence; health survey; smoking; creatinine; risk factor; cancer survivor; body mass; dna; cardiovascular risk; diabetes mellitus; clinical evaluation; medical record; high density lipoprotein cholesterol; metabolic syndrome x; physical activity; physical examination; abdominal obesity; hypogonadism; genetic risk; testis cancer; germ cell tumor; dna extraction; lipid metabolism; testosterone; hypertriglyceridemia; steroid 5alpha reductase; luteinizing hormone; metabolic equivalent; human; male; article; north american; total cholesterol level; cell adhesion molecule 1
Journal Title: Journal of the National Comprehensive Cancer Network
Volume: 16
Issue: 3
ISSN: 1540-1405
Publisher: Harborside Press  
Date Published: 2018-03-01
Start Page: 257
End Page: 265
Language: English
DOI: 10.6004/jnccn.2017.7046
PROVIDER: scopus
PUBMED: 29523664
PMCID: PMC6345519
DOI/URL:
Notes: Publisher-provided DOI does not resolve (as of 7/24/2018) -- Article -- Export Date: 2 April 2018 -- Source: Scopus
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  1. Darren Richard Feldman
    342 Feldman