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Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population

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Abstract

Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non­smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.

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Acknowledgements

This study was sponsored by Pakistan Academy of Sciences (Grant No. 5-9/PAS awarded to RQ) and Radboud University Medical Center, Nijmegen, The Netherlands.

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Authors and Affiliations

  1. Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan

    Syeda Hafiza Benish Ali, Raja Khurram, Maleeha Azam & Raheel Qamar

  2. Pakistan Atomic Energy Commission General Hospital, Islamabad, 44000, Pakistan

    Kashif Sardar Bangash & Khursheed Anwar

  3. Nishtar Medical College & Hospital, Multan, 60000, Pakistan

    Abdur Rauf

  4. Department of Urology, Mayo Hospital, Lahore, 54000, Pakistan

    Muhammad Younis

  5. Department of Urology, Shifa International Hospital, Islamabad, 44000, Pakistan

    Muhammad Athar Khawaja & Saeed Akhter

  6. Department of Radiology, The Children’s Hospital & The Institute of Child Health, Lahore, 54000, Pakistan

    Abid Ali Qureshi

  7. Department for Health Evidence and Department of Urology, Radboud University Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Lambertus A. Kiemeney

  8. Al-Nafees Medical College & Hospital Isra University, Islamabad, 45600, Pakistan

    Raheel Qamar

  9. Pakistan Academy of Sciences, Islamabad, 44000, Pakistan

    Raheel Qamar

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  1. Syeda Hafiza Benish Ali
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  2. Kashif Sardar Bangash
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  3. Abdur Rauf
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  11. Lambertus A. Kiemeney
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Ali, S.H.B., Bangash, K.S., Rauf, A. et al. Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population. Familial Cancer 16, 577–594 (2017). https://doi.org/10.1007/s10689-017-9991-z

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