title: Association of HLA-G +3142 C>G polymorphism and breast cancer in Tunisian population.
abstract: HLA-G is highly expressed in cancer. Also, it is associated to its progression. Here, we explored the relationship between two HLA-G polymorphisms with breast cancer (BC) and tried to make a correlation with sHLA-G levels. We genotyped 104 patients with BC and 83 controls (CTRL) for HLA-G 14-bp insertion/deletion (Ins/Del) and HLA-G +3142 C>G polymorphisms. The mutations were identified with PCR and PCR-RFLP. The sHLA-G dosage was performed on plasma samples by a specific ELISA. A significant association with BC was found concerning the G allele in the +3142 C>G polymorphism (p = 0.0004). The G/G genotype is the protective genotype (1 % in BC patients vs. 13.1 % in CTRL, OR 0.065, 95 % CI 0.008-0.523). No statistically significant differences were observed for the 14-bp Ins/Del polymorphism between BC patients and controls frequencies. The protection by G/G genotype of +3142 C>G polymorphism is maintained in young patients (<50 years, p = 0.0006) and in early-diagnosed BC patients (<50 years, p = 0.0033). In addition, an association was found between the haplotypes inferred by both HLA-G polymorphisms and BC susceptibility. Indeed, the (DelG) haplotype is found as the protective haplotype against BC (OR 0.269, 95 % CI 0.081-0.895, p = 0.023). The ELISA dosage of sHLA-G revealed increased levels in BC compared to CTRL (p < 0.0001). We demonstrated also that sHLA-G is closely associated with advanced stages of BC without significance. sHLA-G is increased in TNM IV and SBR III subgroups. It is also enhanced in patients with a tumor size over 20 mm and in triple-negative patients. Taken together, our findings demonstrate, for the first time, the association of HLA-G +3142 C>G polymorphism with BC susceptibility in Tunisian population. Our results revealed also a potential implication of sHLA-G in advanced stages of BC.
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia. ines.zidi@techemail.com.
authors.forename: Inès
authors.initials: I
authors.lastname: Zidi
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Dziri
authors.affiliation: Department of Medical Oncology, Salah Azaiz Institute, Tunis, Tunisia.
authors.forename: Nour
authors.initials: N
authors.lastname: Zidi
authors.affiliation: Department of Medical Oncology, Salah Azaiz Institute, Tunis, Tunisia.
authors.forename: Refaat
authors.initials: R
authors.lastname: Sebai
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia.|Department of Anatomopathology, Salah Azaiz Institute, Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Boujelebene
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia.
authors.forename: Amna
authors.initials: A
authors.lastname: Ben Hassine
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia.
authors.forename: Hamza
authors.initials: H
authors.lastname: Ben Yahia
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia.
authors.forename: Ahmed Baligh
authors.initials: AB
authors.lastname: Laaribi
authors.affiliation: Laboratoire Microorganismes et Biomolécules Actives, Département de Biologie, Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092, Tunis, Tunisia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Babay
authors.affiliation: Department of Medical Oncology, Salah Azaiz Institute, Tunis, Tunisia.
authors.forename: Hela
authors.initials: H
authors.lastname: Rifi
authors.affiliation: Department of Medical Oncology, Salah Azaiz Institute, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Mezlini
authors.affiliation: LR 11-IPT-06: Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Pasteur Institute of Tunis, Tunis, Tunisia.
authors.forename: Hanene
authors.initials: H
authors.lastname: Chelbi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D012306:Risk; D017384:Sequence Deletion / Q000235:genetics; D014416:Tunisia
chemical_list: D059951:HLA-G Antigens
keywords: +3142 C>G; 14-bp Insertion/deletion; Breast cancer; HLA-G gene; Polymorphism