HLA alleles and lung cancer in a Turkish population

Özbek, Nilgün; Bırınci, Asuman; Karaoglanoglu, Ozden; Çoban, Ahmet Yılmaz; Okumus, Baris; Cakir, Saban; Durupinar, Belma

doi:10.5144/0256-4947.2004.106

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Вместе с тем выявленные взаимосвязи АТ к химическим канцерогенам и стероидным гормонам могут быть детерминированы не только генами цитокинов, но и генами ферментов их биотрансформации, так как последние действительно ассоциированы с РЛ за счет образования реактивных метаболитов указанных соединений [1, 8, 26, 32] и их аддуктов с макромолекулами организма [27,34]. Коль скоро в иммунологическом распознавании гаптенов в составе аддуктов, очевидно, принимают участие молекулы HLA, целесообразно исследовать искомые взаимо связи с генетическим полиморфизмом главного комплекса гистосовместимости, для которого тоже доказаны ассоциации с РЛ [28,30,43]. По-видимому, полное раскрытие механизмов образования АТ к химическим канцерогенам и эндогенным стероидам достижимо при исследовании межгенных взаимодействий ферментов их метаболизма, HLA и цитокинов.…”

Section: Discussionunclassified

Antibodies to Benzo[a]pyrene, Estradiol and Progesterone and Gene Polymorphisms of Cytokines: Associations With Lung Cancer in Men

Глушков¹,

Поленок²,

Гордеева³

et al. 2018

Med. immunol.

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Previous studies have revealed associations of antibodies, specific to chemical carcinogens and steroid hormones with lung cancer in men. However, the mechanisms of their formation and action were remained unclear. In particular, the relationships between antibodies and gene polymorphisms of cytokines were unknown. The purpose of this study was to identify possible associations between occurrence of A class antibodies, specific to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es and IgA-Pg), and frequency of genetic polymorphisms of IL1RN VNTR, IL1В (rs1143634, rs16944), IL4 VNTR, IL6 (rs1800795), IL10 (rs1800896), TNFA (rs1800629, rs361525) genes in healthy male smokers and lung cancer patients. We have examined 381 men with non-small cell lung cancer and 158 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies was performed. Analysis of polymorphic loci of IL1RN (VNTR, intron 2), IL4 (VNTR, intron 3) was performed by means of conventional PCR; IL1В (rs1143634, rs16944), IL6 (rs1800795) SNPs were detected by RFLP, and IL10 (rs1800896), TNFA (rs1800629, rs361525) genotyping was carried out with TaqMan Real-time PCR. Results of the study have shown that the proportion of cases with high level of IgA-Pg and low levels of both IgA-Bp and IgA-Es among the lung cancer patients was lower than in healthy men (OR = 0.31, p < 0.0001). Vice versa, the ratio of cases with high levels of both IgA-Bp and IgA-Es and low levels of IgA-Pg was higher in lung cancer patients (OR = 3.6, p < 0.0001). No relationships were revealed between the levels of antibodies, and rates of genetic polymorphisms for the studied cytokines in both groups of men. At the same time, the detected associations of IgA-Bp, IgA-Es and IgA-Pg with lung cancer proved to be significant only in carriers of certain cytokine genotypes, e.g., in AG IL10 heterozygotes (OR = 5.1, p < 0.0001). In conclusion, these results provide indirect evidence that IgA-Bp and IgA-Es could stimulate initiation and promotion of lung carcinogenesis. On the contrary, IgA-Pg could inhibit the promotion of carcinogenesis. Immunoassay of these antibodies combined with molecular biology studies of IL10 gene variants are recommended for the lung cancer risk assessment.

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Section: Discussionunclassified

Antibodies to Benzo[a]pyrene, Estradiol and Progesterone and Gene Polymorphisms of Cytokines: Associations With Lung Cancer in Men

Глушков¹,

Поленок²,

Гордеева³

et al. 2018

Med. immunol.

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“…Кроме того, обнаружена высокая частота носительства аллеля HLA-DRB1*04 у пациентов с папиллярным раком щитовидной железы по сравнению со здоровой когортой [20]. Вариабельность генов главного комплекса гистосовместимости также может быть ассоциирована с развитием других новообразований: рака шейки матки [21], желудка [22], а также играть роль в определении прогноза при раке легких [23] и меланоме кожи [24].…”

Section: роль генов системы Hla: от аутоиммунных заболеваний до Covid-19unclassified

The role of HLA genes: from autoimmune diseases to COVID-19

Troshina

Yukina

Nuralieva

et al. 2020

Probl Endokrinol (Mosk)

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Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II — to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm» in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.

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“…As far as NSCLC, the significant association between a prolonged survival and the expression of HLA-Aw19 or HLA-B5 was first reported in 1975 [16]. Since then, many reports have discussed that several HLA alleles influenced the survival of lung cancer patients [17][18][19][20][21][22][23][24]. However, these studies analyzed a relatively small number of patients.…”

Section: Introductionmentioning

confidence: 98%