Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals

Kamalesh Dattaram Mumbrekar, Hassan Venkatesh Goutham, Bejadi Manjunath Vadhiraja, Satish Rao Bola Sadashiva

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it. Methods: By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity. Results: The rs2267437 polymorphisms in XRCC6 was associated (P = 0.0326) with increased DSB induction while rs1805388 in LIG4 (P = 0.0240) was associated with increased radioresistance. Further, multiple risk alleles decreased the DSB repair capacity in an additive manner. Polymorphisms in candidate DSB repair genes can act individually or in combination to the efficacy of DSB repair process, resulting in variation of cellular radiosensitivity. Conclusions: Current study suggests that γ-H2AX assay may fulfil the role of a rapid and sensitive biomarker that can be used for epidemiological studies to measure variations in radiosensitivity. DSB repair gene polymorphisms can impact the formation and repair of DSBs. Impact: γ-H2AX foci analysis as well as DSBs repair gene polymorphisms can be used to assess cellular radiosensitivity, which will be useful in population risk assessment, disease prediction, individualization of radiotherapy and also in setting the radiation protection standards.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalDNA Repair
Volume40
DOIs
Publication statusPublished - 01-04-2016

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Lymphocytes
Radiation Tolerance
Polymorphism
Repair
Genes
Phenotype
Radiotherapy
Assays
Radiation protection
Radiation Protection
Automatic teller machines
Biomarkers
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione
Risk assessment
Single Nucleotide Polymorphism
Epidemiologic Studies
Alleles
Genotype
Population
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals",
abstract = "Background: A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it. Methods: By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity. Results: The rs2267437 polymorphisms in XRCC6 was associated (P = 0.0326) with increased DSB induction while rs1805388 in LIG4 (P = 0.0240) was associated with increased radioresistance. Further, multiple risk alleles decreased the DSB repair capacity in an additive manner. Polymorphisms in candidate DSB repair genes can act individually or in combination to the efficacy of DSB repair process, resulting in variation of cellular radiosensitivity. Conclusions: Current study suggests that γ-H2AX assay may fulfil the role of a rapid and sensitive biomarker that can be used for epidemiological studies to measure variations in radiosensitivity. DSB repair gene polymorphisms can impact the formation and repair of DSBs. Impact: γ-H2AX foci analysis as well as DSBs repair gene polymorphisms can be used to assess cellular radiosensitivity, which will be useful in population risk assessment, disease prediction, individualization of radiotherapy and also in setting the radiation protection standards.",
author = "Mumbrekar, {Kamalesh Dattaram} and Goutham, {Hassan Venkatesh} and Vadhiraja, {Bejadi Manjunath} and {Bola Sadashiva}, {Satish Rao}",
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Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals. / Mumbrekar, Kamalesh Dattaram; Goutham, Hassan Venkatesh; Vadhiraja, Bejadi Manjunath; Bola Sadashiva, Satish Rao.

In: DNA Repair, Vol. 40, 01.04.2016, p. 27-34.

Research output: Contribution to journalArticle

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T1 - Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals

AU - Mumbrekar, Kamalesh Dattaram

AU - Goutham, Hassan Venkatesh

AU - Vadhiraja, Bejadi Manjunath

AU - Bola Sadashiva, Satish Rao

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N2 - Background: A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it. Methods: By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity. Results: The rs2267437 polymorphisms in XRCC6 was associated (P = 0.0326) with increased DSB induction while rs1805388 in LIG4 (P = 0.0240) was associated with increased radioresistance. Further, multiple risk alleles decreased the DSB repair capacity in an additive manner. Polymorphisms in candidate DSB repair genes can act individually or in combination to the efficacy of DSB repair process, resulting in variation of cellular radiosensitivity. Conclusions: Current study suggests that γ-H2AX assay may fulfil the role of a rapid and sensitive biomarker that can be used for epidemiological studies to measure variations in radiosensitivity. DSB repair gene polymorphisms can impact the formation and repair of DSBs. Impact: γ-H2AX foci analysis as well as DSBs repair gene polymorphisms can be used to assess cellular radiosensitivity, which will be useful in population risk assessment, disease prediction, individualization of radiotherapy and also in setting the radiation protection standards.

AB - Background: A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it. Methods: By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity. Results: The rs2267437 polymorphisms in XRCC6 was associated (P = 0.0326) with increased DSB induction while rs1805388 in LIG4 (P = 0.0240) was associated with increased radioresistance. Further, multiple risk alleles decreased the DSB repair capacity in an additive manner. Polymorphisms in candidate DSB repair genes can act individually or in combination to the efficacy of DSB repair process, resulting in variation of cellular radiosensitivity. Conclusions: Current study suggests that γ-H2AX assay may fulfil the role of a rapid and sensitive biomarker that can be used for epidemiological studies to measure variations in radiosensitivity. DSB repair gene polymorphisms can impact the formation and repair of DSBs. Impact: γ-H2AX foci analysis as well as DSBs repair gene polymorphisms can be used to assess cellular radiosensitivity, which will be useful in population risk assessment, disease prediction, individualization of radiotherapy and also in setting the radiation protection standards.

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