Presence of the human leukocyte antigen class II gene DRB1*1101 predicts interferon gamma levels and disease recurrence in melanoma patients.
BACKGROUND
Increased interferon gamma (IFN-gamma) levels are an independent predictor of melanoma recurrence. Human leukocyte antigen (HLA) class II genes can regulate cytokine production; we investigated whether these genes would predict IFN-gamma levels and recurrence in melanoma patients.


METHODS
Of 591 patients who presented with localized melanoma, 579 underwent identification of HLA class II alleles; 233 melanoma patients and 90 controls underwent determination of plasma IFN-gamma levels. HLA class II genes were examined for association with IFN-gamma levels and disease recurrence.


RESULTS
After a median follow-up of 60 months, melanoma patients with IFN-gamma levels above the mean control value were more likely to have developed disease recurrence compared with patients with levels below the mean. The HLA class II gene HLA-DRB1*1101 was the strongest predictor of recurrence, and HLA-DRB1*1101-positive melanoma patients had increased levels of IFN-gamma compared with patients lacking the gene.


CONCLUSIONS
Among patients with localized melanoma, both HLA-DRB1*1101 and increased IFN-gamma levels were associated with an increased risk for recurrence; HLA-DRB1*1101-positive patients had relatively increased levels of IFN-gamma. HLA class II genes may mediate cytokine production in melanoma patients, and this mechanism may help determine the risk of disease recurrence.
Lee
Jeffrey E
JE
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. jelee@notes.mdacc.tmc.edu
Abdalla
Joseph
J
Porter
Geoffrey A
GA
Bradford
Loretta
L
Grimm
Elizabeth A
EA
Reveille
John D
JD
Mansfield
Paul F
PF
Gershenwald
Jeffrey E
JE
Ross
Merrick I
MI
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics*; D011379:Prognosis; D013781:Texas / Q000453:epidemiology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007371:Interferon-gamma