Reserch of the gene polymorphism TOX3 / LOC643714 and the risk of breast cancer development in persons exposed to ionizing radiation after Chornobyl disaster

Probl Radiac Med Radiobiol. 2017 Dec:22:450-462.
[Article in English, Ukrainian]

Abstract

Objective: The objective of this work was to identify and compare the polymorphism of the rs3803662 polymorphism of the TOX3/LOC643714 gene in breast cancer patients who have undergone ionizing radiation due to the Chornobyl accident and in patients without ionizing radiation (IR) in the history.

Materials and methods: The determination of the rs3803662 polymorphism of the TOX3/LOC643714 gene was per formed by polymerase chain reaction (PCR) in 83 patients with breast cancer: 42 subjects who were exposed to ion izing radiation due to the Chornobyl accident, 41 people without ionizing radiation in history and 17 controls in Ukraine without cancer pathology. In order to compare the obtained data on spontaneous and radiation associated breast cancer and to calculate the differences in the frequencies of alleles and the risk of oncopathology, data from literature on control groups of the populations of the Russian Federation, Sweden, and the United Kingdom were used.

Results: Comparing with the literature data and the group of exposed subjects, the homozygous carriers of the minor alleles of the TOX3/LOC643714 ТТ gene revealed an increased risk of developing breast cancer: OR = 2.89, p = 0.02 (CI 95% 1.17 7,16). In subjects without the influence of IR in history, the carrier of homozygous minor axis of the gene TOX3/LOC643714 ТТ is also associated with the risk of breast cancer: OR = 3.83, p = 0.0002 (CI 95% 0.82-14.14). In the homozygous carriers of the minor alleles of the TOX3 / LOC643714 gene exposed to IR, there was no increase in the risk of developing breast cancer (OR = 0.65, p = 0.46, CI 95% 0.21-2.04) compared with the con trol group of Ukrainian population.

Conclusions: The carrier of homozygous minor alleles of the TOX3/LOC643714 gene is not a risk factor for the devel opment of breast cancer under conditions of exposure to ionizing radiation in the study group of the Ukrainian population.

Meta. Metoiu roboty bulo: vyznachyty ta porivniaty osoblyvosti polimorfizmu rs3803662 gena TOX3/LOC643714 u khvorykh na rak molochnoï zalozy (RMZ), iaki zaznaly diï ionizuiuchoï radiatsiï vnaslidok avariï na Chornobyl's'kiy̆ AES, ta u khvorykh bez vplyvu ionizuiuchogo vyprominiuvannia (IV) v anamnezi.Materialy i metody. Vyznachennia polimorfizmu rs3803662 gena TOX3/LOC643714 provodyly shliakhom polimeraznoï lantsiugovoï reaktsiï (PLR) u 83 khvorykh na RMZ: 42 osib, iaki zaznaly diï ionizuiuchoï radiatsiï vnaslidok avariï na Chornobyl's'kiy̆ AES, 41 osoby bez vplyvu ionizuiuchogo vyprominennia v anamnezi ta 17 osib kontrol'noï grupy zhyteliv Ukraïny bez onkopatologiï. Dlia porivniannia otrymanykh danykh shchodo spontannogo i radiatsiy̆no asotsiy̆ova nogo RMZ ta rozrakhunku vidminnostey̆ chastot aleliv i ryzyku vynyknennia onkopatologiï vykorystovuvaly dani literatury shchodo kontrol'nykh grup populiatsiy̆ Rosiy̆s'koï Federatsiï, Shvetsiï, Velykoï Brytaniï.Rezul'taty. Pry porivnianni z danymy literatury ta grupoiu osib, iaki zaznaly vplyvu IV, u gomozygotnykh nosiïv minornykh aleliv gena TOX3/LOC643714 TT vyiavleno zbil'shennia ryzyku rozvytku RMZ: OR = 2,89, p = 0,02 (CI 95 % 1,17–7,16).U osib bez vplyvu IV v anamnezi nosiy̆stvo gomozygotnykh minornykh aleliv gena TOX3/LOC643714 TT takozh asotsiiuiet'sia z ryzykom vynyknennia RMZ: OR = 3,83, r = 0,0002 (CI 95 % 0,82–14,14). U gomozygotnykh nosiïv minor nykh aleliv gena TOX3/LOC643714, iaki zaznaly vplyvu IV, ne vyiavleno zbil'shennia ryzyku rozvytku RMZ (OR = 0,65, p = 0,46, CI 95 % 0,21–2,04) porivniano z kontrol'noiu grupoiu ukraïns'koï populiatsiï.Vysnovky. Nosiy̆stvo gomozygotnykh minornykh aleliv gena TOX3/LOC643714 ne ie faktorom ryzyku rozvytku RShchZ za umov vplyvu ionizuiuchogo vyprominiuvannia v doslidzheniy̆ grupi ukraïns'koï populiatsiï.

Keywords: accident at the Chornobyl Nuclear Power Plant; breast cancer; genetic polymorphism; TOX3/LOC643714.

MeSH terms

  • Adult
  • Alleles
  • Apoptosis Regulatory Proteins
  • Breast Neoplasms / etiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Chernobyl Nuclear Accident*
  • Female
  • Gene Expression
  • Gene Frequency
  • Genotype
  • High Mobility Group Proteins
  • Homozygote
  • Humans
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Radiation Dosage
  • Radiation Exposure / adverse effects*
  • Receptors, Progesterone / genetics*
  • Risk Factors
  • Survivors
  • Trans-Activators
  • Ukraine

Substances

  • Apoptosis Regulatory Proteins
  • High Mobility Group Proteins
  • Receptors, Progesterone
  • TOX3 protein, human
  • Trans-Activators