Negative Association of the HLA-DQB1*02 Allele with Breast Cancer Development among Jordanians

  • Atoum, Manar Fayiz (Department of Medical Laboratory Sciences, Faculty of Allied Health, Hashemite University) ;
  • Tanashat, Reem Qasem (Department of Medical Laboratory Sciences, Faculty of Allied Health, Hashemite University) ;
  • Mahmoud, Sameer Al Haj (Department of Microbiology, Hashemite University)
  • Published : 2013.11.30


Background: In the literature, data concerning the relationship between breast cancer and HLA class II gene polymorphisms are limited, so the aim of this study was to determine if HLA-DQB1 and HLA-DRB1 MHC class-II alleles may confer susceptibility or resistance to the disease among Jordanian females. Materials and Methods: This case control study enrolled 56 Royal Hospital breast cancer patients and 60 age matched healthy controls, all of whom provided blood samples (2011-2013). A questionnaire was filled after signing a consent form and DNA was extracted, nucleic acids being amplified for assessment of HLA-DQB1 and HLA-DRB1 alleles by muliplex INNO-LiPA and allele typing carried out by reverse hybridization. Comparison of HLA-DQB1 and HLA-DRB1 allele distributions was carried out with paired t-test and chi-square statistics. Risk factors were assessed by odd ratios with 95% confidence intervals. Results: A significant negative correlation was observed between $HLADQB1^*$ 02 alleles and breast cancers (p=0.013). No significant associations were observed among $HLADQB1^*$ 03, 04, 05 and 06 or among $HLA-DRB1^*$ 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15. Conclusions: $HLADQB1^*$ 02 alleles may provide positive protection against breast tumor risk among Jordanians, but not $HLADQB1^*$ 03, 04, 05 and 06 or $HLA-DRB1^*$ 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15 alleles.


HLA-DQB1;HLA-DRB1;alleles;breast cancer;susceptibility


  1. Alfonso C, Karlsson L (2000). Nonclassical MHC class II molecules. Annu Rev Immunol, 18, 113-42.
  2. Amar A, Kwon OJ, Motro U, et al (1999). Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel. Hum Immunol, 60, 723-30.
  3. Atoum M, Hourani H, Shoter A, et al (2010). TNM staging and classification (familial and non-familial) of breast cancer in Jordanian females. Indian J Cancer, 47, 194-8.
  4. Bustin SA, Li SR, Phillips S, Dorudi S (2001). Expression of HLA class II in colorectal cancer: evidence for enhanced immunogenicity of microsatellite-instability-positive tumours. Tumour Biol, 22, 294-8.
  5. Cantu De Leon D, Perez-Montiel D, Villavicencio V, et al (2009). Hgh resolution human leukocyte antigen (HLA) classes I and class II typing in Mexican mestizo women with sporadic breast cancer: case-control study. BMC Cancer, 9, 48.
  6. Chaudhuri S, Cariappa A, Tang M, et al (2000). Genetic susceptibility to breast HLADQB03032 and HLA DRB1*111 may represent protective alleles. Proc Natl Acad Sci USA, 97, 11451-4.
  7. Chen PC, Tsai EM, Er TK, et al (2007). HLA-DQA1 and DQB1 allele typing in southern Taiwanese women with breast cancer. Clin Chem Lab Med, 45, 611-4.
  8. De Vreese K, Barylski R, Pughe F, et al (2004). Performance characteristics of updated INNO- LiPA assays for molecular typing of human leukocyte antigen A (HLA-A), HLA-B, and HLA-DQB1 alleles. Clin Diagn Lab Immunol, 11, 430-2.
  9. De Vreese KR, Ramanakumar AV, Koushik A, et al (2012). Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix. Int J Cancer, 131, 312-9.
  10. Downs-Holmes C, Silverman P (2011). Breast cancer: overview and updates. Nurse Pract, 36, 20-6.
  11. El-Akawi ZJ, Al-Hattab DM, Migdady Y MA (2010). Frequency of HLA-DQA1*0501 and DQB1*0201 alleles in patients with coeliac disease, their first-degree relatives and controls in Jordan. Ann Trop Paediatr, 30, 305-9.
  12. Ghaderi A, Talei A, Gharesi-Fard B, et al (2001). HLA-DBR 1 alleles and the susceptibility of Iranian patients with breast cancer. Pathol Oncol Res, 7, 39-41.
  13. Goa J, Lin Y, Qiu C, et al (2003). Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects. Chin Med J (Engl), 116, 1078-82.
  14. Gun FD, Ozturk OG, Polat A, Polat G (2012). HLA class II allele frequencies in Turkish breast cancer patients. Med Oncol, 29, 466-71.
  15. Harrath AB, Loueslati BY, Troudi W, et al (2006). HLA class II polymorphism: protective or risk factors to breast cancer in Tunisia. Pathol Oncol Res, 12, 79-81.
  16. Horton R, Wilming L, Rand V, et al (2004). Gene map of the extended human MHC. Nat Rev Genet, 5, 889-99.
  17. Huang HS, Peng JT, She JY, et al (1995). HLA-encoded susceptibility to insulin-dependent diabetes mellitus is determined by DR and DQ genes as well as their linkage disequilibria in a Chinese population. Hum Immunol, 44, 210-9.
  18. Jiang J, Li N, Shen Y, et al (2013). Genetic variants in HLA-DP/DQ contribute to risk of cervical cancer: A two-stage study in Chinese women. Gynecol Oncol, 129, 401-5.
  19. Lee JE, Lowy AM, Thompson WA, et al (1996). Association of gastric adenocarcinoma with the HLA class II gene DQB10301. Gastroenterology, 111, 426-32.
  20. Kubler K, Arndt PF, Wardelmann E, et al (2006). HLA-class II haplotype associations with ovarian cancer. Int J Cancer, 119, 2980-5.
  21. Lavado R, Benavides M, Villar E, et al (2005). The HLA-B7 allele confers susceptibility to breast cancer in Spanish women. Immunol Lett, 101, 223-5.
  22. Levine F, Erlich H, Mach B, et al (1985). Deletion mapping of HLA and chromosome 6p genes. Proc Natl Acad Sci USA, 82, 3741-5.
  23. Liang J, Chen P, Hu Z, et al (2008). Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women. Carcinogenesis, 29, 2341-6.
  24. Mahmoodi M, Nahvi H, Mahmoudi M, et al (2012). HLA-DRB1,DQA1 and DQB1 allele and haplotype frequencies in female patients with early onset breast cancer. Pathol Oncol Res, 18, 49-55.
  25. Ragoussis J, Loemer KB, Pohla H, et al (1985). A physical map including a new class I gene (cda12) of the human major histocompatibility complex (A2/B13 haplotype) derived from a monosomy 6 mutant cell line. Genomics, 4, 301-8.
  26. Redondo M, Garcia J, Villar E, et al (2003). Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis. Hum Pathol, 34, 1283-9.
  27. Scanlan MJ, Gout I, Gordon CM, et al (2001). Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. Cancer Immun, 30, 1-4.
  28. Watanabe A MA, Oda JM, Amarante MK, Cesar Voltarelli J (2010). Regulatory T cells and breast cancer: implications for immunopathogenesis. Cancer Metastasis Rev, 29, 569-79.
  29. Wolkersdorfer T, Fussel M, Kiesslich T, et al (2011). MHC class II genotype- and MHC class I and II phenotype-related parameters in sporadiccolorectal cancer. Oncol Rep, 26, 1165-71.
  30. Yang XX, Pan HZ, Li PY, et al (2011). HLA class II variants in Chinese breast cancer patients. Asian Pac J Cancer Prev, 12, 3075-9.
  31. Zaloudik J, Moore M, Ghosh AK, et al (1988). DNA content and MHC class II antigen expression in malignant melanoma: clinical course. J Clin Pathol, 41, 1078-84.