Clinical and genetic risk factors for adverse metabolic outcomes in north American testicular cancer survivors

Mohammad Abu Zaid, Wambui G. Gathirua-Mwangi, Chunkit Fung, Patrick Monahan, Omar El-Charif, Annalynn M. Williams, Darren R. Feldman, Robert J. Hamilton, David J. Vaughn, Clair J. Beard, Ryan Cook, Sandra K. Althouse, Shirin Ardeshir-Rouhani-Fard, Paul C. Dinh, Howard D. Sesso, Lawrence Einhorn, Sophie D. Fossa, Lois B. Travis

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)257-265
Number of pages9
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2018

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Testicular Neoplasms
Survivors
Abdominal Obesity
Cardiovascular Diseases
HDL Lipoproteins
Hypertension
LDL Cholesterol
Testosterone
Fats
Hypogonadism
Nutrition Surveys
Hypertriglyceridemia
Cell Adhesion Molecules
HDL Cholesterol
Physical Examination
Single Nucleotide Polymorphism
Oxidoreductases
Body Mass Index
Multivariate Analysis
Odds Ratio

ASJC Scopus subject areas

  • Oncology

Cite this

Clinical and genetic risk factors for adverse metabolic outcomes in north American testicular cancer survivors. / Zaid, Mohammad Abu; Gathirua-Mwangi, Wambui G.; Fung, Chunkit; Monahan, Patrick; El-Charif, Omar; Williams, Annalynn M.; Feldman, Darren R.; Hamilton, Robert J.; Vaughn, David J.; Beard, Clair J.; Cook, Ryan; Althouse, Sandra K.; Ardeshir-Rouhani-Fard, Shirin; Dinh, Paul C.; Sesso, Howard D.; Einhorn, Lawrence; Fossa, Sophie D.; Travis, Lois B.

In: JNCCN Journal of the National Comprehensive Cancer Network, Vol. 16, No. 3, 01.03.2018, p. 257-265.

Research output: Contribution to journalArticle

Zaid, MA, Gathirua-Mwangi, WG, Fung, C, Monahan, P, El-Charif, O, Williams, AM, Feldman, DR, Hamilton, RJ, Vaughn, DJ, Beard, CJ, Cook, R, Althouse, SK, Ardeshir-Rouhani-Fard, S, Dinh, PC, Sesso, HD, Einhorn, L, Fossa, SD & Travis, LB 2018, 'Clinical and genetic risk factors for adverse metabolic outcomes in north American testicular cancer survivors', JNCCN Journal of the National Comprehensive Cancer Network, vol. 16, no. 3, pp. 257-265. https://doi.org/10.6004/jnccn.2017.7046
Zaid, Mohammad Abu ; Gathirua-Mwangi, Wambui G. ; Fung, Chunkit ; Monahan, Patrick ; El-Charif, Omar ; Williams, Annalynn M. ; Feldman, Darren R. ; Hamilton, Robert J. ; Vaughn, David J. ; Beard, Clair J. ; Cook, Ryan ; Althouse, Sandra K. ; Ardeshir-Rouhani-Fard, Shirin ; Dinh, Paul C. ; Sesso, Howard D. ; Einhorn, Lawrence ; Fossa, Sophie D. ; Travis, Lois B. / Clinical and genetic risk factors for adverse metabolic outcomes in north American testicular cancer survivors. In: JNCCN Journal of the National Comprehensive Cancer Network. 2018 ; Vol. 16, No. 3. pp. 257-265.
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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.",
author = "Zaid, {Mohammad Abu} and Gathirua-Mwangi, {Wambui G.} and Chunkit Fung and Patrick Monahan and Omar El-Charif and Williams, {Annalynn M.} and Feldman, {Darren R.} and Hamilton, {Robert J.} and Vaughn, {David J.} and Beard, {Clair J.} and Ryan Cook and Althouse, {Sandra K.} and Shirin Ardeshir-Rouhani-Fard and Dinh, {Paul C.} and Sesso, {Howard D.} and Lawrence Einhorn and Fossa, {Sophie D.} and Travis, {Lois B.}",
year = "2018",
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TY - JOUR

T1 - Clinical and genetic risk factors for adverse metabolic outcomes in north American testicular cancer survivors

AU - Zaid, Mohammad Abu

AU - Gathirua-Mwangi, Wambui G.

AU - Fung, Chunkit

AU - Monahan, Patrick

AU - El-Charif, Omar

AU - Williams, Annalynn M.

AU - Feldman, Darren R.

AU - Hamilton, Robert J.

AU - Vaughn, David J.

AU - Beard, Clair J.

AU - Cook, Ryan

AU - Althouse, Sandra K.

AU - Ardeshir-Rouhani-Fard, Shirin

AU - Dinh, Paul C.

AU - Sesso, Howard D.

AU - Einhorn, Lawrence

AU - Fossa, Sophie D.

AU - Travis, Lois B.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

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