Breast cancer (BC) is one of the common malignant tumors of women in the world. The incidence rate of this cancer increased in frequency in the last years in Iraq. Several human leukocyte antigen (HLA) are associated with susceptibility or protection in BC, the particular allele varies depending on the racial groups. Many etiological agents are proposed to play a role in BC pathogenecity, one of these factors is cytokines. Permanent synthesis and release of these cytokines leads to augmentation of their serum concentration
that might be utilized as a marker of immunity status and immune system activation,in prognosis and monitoring of the course of cancer. This is a prospective study was carried out to investigate the possible
association of human leukocyte antigen class I and II alleles with BC and to evaluate the serum levels of some cytokines with disease activity. A total of 45 female patients with BC were studied, their ages range
from 28-73 years with a mean age of 48.1 ± 5.2 years. Fifteen point five percent (15.5%) of patients had positive family history of BC. Two control groups were included in this study for comparison. The first group included (23) apparantly healthy individuals who were age and sex matched with patients and (12) patients with benign breast lesions 6 cases with fibrocystic disease and 6 with fibroadenoma) were chosen as
second control group. Blood samples were collected from patients and controls, DNA was extracted, and then HLA genotyping was performed by polymerase chain reaction-specific sequence primers (PCR- SSP).
Laboratory investigations including PCR-SSP test of HLA- typing for both patient and control groups had been done to observe the possible association of some HLA-alleles with BC. Moreover, enzyme-linked
immunosorbent assay (ELISA) test was carried out for estimation the serum levels of innate (IL-1_, IL-8, TNF_), Th1 (IFN_ and IL-12), and Th2 (IL-6, IL-10) cells-related cytokines in all studied groups. The present study was showed a significant association of HLAA* 03010101-07, 09-11N, 13-16 allele and BC patients as compared with healthy and control patients (P= 0.041, P=0.04) respectively. In addition, the frequency of HLA B and Cw alleles in patients showed no statistically significant differences when compared with the both control groups. Another interesting finding was the frequency of DR*010101, 0102, 0201-0204, 04-13 and DQB1*0401, 02 alleles showed significant low frequency in patients when compared with healthy control (P=0.047 for both alleles), suggesting that both alleles may confer protective effects against disease.
Furthermore, statistical analysis showed no positive association of HLA-alleles with tumor grading and with aging (prmenopause and postmenopause groups), this might in part, resulted from the limited number
of investigated patients in this study. In addition, the comparison between BC cases with negative estrogen/
progesterone receptors and that with positive receptors according to HLAalleles frequency was shown a significantly higher frequency of only A*03010101-07,09-11N,13-16 allele among the first group as compared with the later P= <0.05. Regarding statistical analysis of serum cytokines levels: a significant
elevation was noticed in the median serum level of innate and Th2-cells related cytokines (IL-1_, IL-8, TNF_, IL-6 and IL-10) in patients as compared with control groups, this elevation was significantly associated
with poor prognostic factors including advanced stage and ER/PR-negative status, which may be a clue for their prognostic value in BC. On the other hand, there was a decrease in the median of serum level of Th1-cells related cytokines (INF_ and IL-12) in patients as compared with control groups, in addition there was no association between the decrease in cytokines (INF_ and IL-12) serum levels and the certain prognostic factors including advanced stage and ER&PR status.The serum levels of ILs-(1, 6 and 10) were significantly higher in*03010101-07, 09-11N, 13-16 allele positive patients as compared with negatives. Where as the levels of ILs-(1 and 10) were significantly higher in Cw*04010101-0102, 03-09N, 10-13 and B*5208 allele positive patients respectively as compared with negatives. In conclusion, these data suggest that HLA- A*03010101-07, 09-11N, 13-16 allele may be considered as a risk factor in BC, while HLA–
DR*010101, 0102, 0201-0204, 04-13 and DQB1*0401, 02 alleles may confer protective effects against the disease. In addition, present data suggest that innate and Th2-cells related cytokines could be involved with aggressive behavior of BC, these findings would lend support to the concept of immune surveillance as a critical component involved in tumorigenesis.