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Significant association of TOX3/LOC643714 locus-rs3803662 and breast cancer risk in a cohort of Iranian population

  • Amir Tajbakhsh
  • Fahimeh Afzal Javan
  • Mahdi Rivandi
  • Atefeh Moezzi
  • Soheila Abedini
  • Mahla Asghari
  • Zahra Farjami
  • Hosein Soltanian
  • Fatemeh Homaei Shandiz
  • Mohammad Mahdi Kooshyar
  • Alireza Pasdar
Original Article
  • 17 Downloads

Abstract

Genome-wide association studies normally focus on low penetrance and moderate to high-frequency single nucleotide polymorphisms (SNPs), which lead to genetic susceptibility to breast cancer. In this regard, the T allele of rs3803662 has been associated with breast cancer risk and with lower expression level of TOX3. We aimed to assess the risk of breast cancer associated with this polymorphism in an Iranian population. Using Tetra Primer ARMS PCR, rs3803662 was analyzed in a total of 943 individuals (430 cases and 513 healthy controls form North East of Iran). Allele frequencies and genotype distribution were analyzed in case and control samples to find out any association using the Chi-squared test and Logistic regression. All cases were pathologically confirmed; all controls were mainly healthy individuals. Genotype frequencies were found to be in agreement with HWE in controls and cases. TOX3-rs3803662 SNP was associated with breast cancer risk in our study (T vs. C allele contrast model: OR 1.36, 95% CI 1.12–1.64, Pvalue = 0.002; TT vs. CT + TT dominant model: OR 0.67, 95% CI 0.51–0.87, Pvalue = 0.003; TT vs. CT + CC recessive model: OR 1.54, 95% CI 1.02–2.30, Pvlue = 0.036). Moreover, after adjusting for age, BMI, history of previous cancer and also family history of cancer, all results, except for the recessive model, were remained significant. TOX3-rs3803662, may confer some degrees of risk of breast cancer in Iranian population. This finding is in line with similar results in other populations. It highlights the importance of TOX3 pathway in tumorigenesis.

Keywords

TOX3/ TNRC9 Cancer risk Breast carcinoma Outcomes 

Abbreviations

SNPs

Single nucleotide polymorphisms

CREB

CAMP response element binding protein

CRE

CREB-binding protein

ER

Estrogen-responsive

MD

Mammographic density

ARMS

Amplification refractory mutation system

HWE

Hardy–Weinberg equilibrium

OR

Odds ratio

CI

Confidence interval

LOH

Loss of heterozygosity

GWASs

Genome-wide association studies

Ca2+

Calcium

EGFR

Epidermal growth factor receptor

FOXF2

Forkhead box 2

PgR

Progesterone receptor

TNBC

Triple-negative breast cancer

FFPE

Formalin-fixed, paraffin-embedded

SCC

Squamous cell carcinoma

BCS

Breast conservative surgery

MRM

Modified radical mastectomy.

Notes

Acknowledgements

This manuscript was based on PhD thesis of Mr. Amir Tajbakhsh and was supported by the Mashhad University of science (Grant Number: 940789).

Funding

This study was supported by Mashhad University of Medical Sciences (Grant No. 940789).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Amir Tajbakhsh
    • 1
    • 2
    • 3
  • Fahimeh Afzal Javan
    • 1
    • 2
  • Mahdi Rivandi
    • 1
    • 2
  • Atefeh Moezzi
    • 1
    • 2
  • Soheila Abedini
    • 2
    • 6
  • Mahla Asghari
    • 2
    • 6
  • Zahra Farjami
    • 1
    • 2
  • Hosein Soltanian
    • 2
  • Fatemeh Homaei Shandiz
    • 4
  • Mohammad Mahdi Kooshyar
    • 5
  • Alireza Pasdar
    • 1
    • 6
    • 7
  1. 1.Department of Modern Sciences & Technologies, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  2. 2.Student Research Committee, Department of Modern Sciences & Technologies, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  3. 3.Young Researchers and Elite Club, Yasooj BranchIslamic Azad UniversityYasoojIran
  4. 4.Solid Tumor Treatment Research CenterMashhad University of Medical UniversityMashhadIran
  5. 5.Department of Haematology-Oncology, Imam Reza HospitalMashhad University of Medical SciencesMashhadIran
  6. 6.Department of Medical Genetics, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  7. 7.Division of Applied Medicine, Faculty of MedicineUniversity of AberdeenAberdeenUK

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