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Assessing Colorectal Cancer Susceptibility in Kashmir, India: Insights from Xenobiotic Metabolism Gene Variants and Family Cancer History—A Comprehensive Case–Control Study

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Abstract

A family history of cancer(FHC) is a known risk factor for CRC with both genetic and other factors. A case–control study was conducted to assess the association between FHC and CRC risk in Kashmir, India, with a detailed analysis of epidemiological data and information on multiple gene polymorphisms. We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 246 histopathologically confirmed CRC cases and 246 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The study participants diagnosed with colorectal cancer (CRC) exhibited a robust correlation with a positive family history of CRC. In terms of gender-based analysis, it was observed that males with CRC and a family history of CRC had an odds ratio of 16.45 (95% CI; 2.14–126.26), whereas females exhibited an odds ratio of 4.11 (95% CI; 0.84–20.03). Furthermore, individuals with affected parents showed an almost fivefold increase (OR = 4.70, 95% CI: 0.98–1.06), underscoring the substantial association. Our study unveiled significant correlations between Xenobiotic gene variants and the risk of colorectal cancer (CRC). Among individuals without a family history (FH-), those with the CYP2A6a gene variant (*1A/*6 and *6/*6 genotypes) exhibited a substantial 2.03-fold increase in CRC risk (OR = 2.03, 95% CI = 1.17–3.51, p-value = 0.011). Turning to the CYP2A6b gene variant, FH- individuals carrying *1/*4 and *4/*4 genotypes demonstrated a modestly increased CRC risk (OR = 1.51, 95% CI = 0.98–2.39, p-value = 0.069), suggesting a potential association. On the similar pattern, among FH + individuals, the GSTT1− genotype displayed a notably increased CRC risk (OR = 5.1, 95% CI = 0.61–42.38, p-value = 0.014). FH- individuals with the GSTM1− genotype showcased a substantially increased CRC risk (OR = 3.98, 95% CI = 2.52–6.23, p-value = 0.001), whereas the association lacked statistical significance in FH + individuals (OR = 2.22, 95% CI = 0.56–8.76, p-value = 0.258). Our study revealed that FHC was strongly associated with the elevated risk of having CRC in Kashmir. The prevalence of genetic factors were also found in this association.

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Acknowledgements

We are highly indebted to all the study participants who willingly participated in this study.

Funding

This study was financially supported by an Intramural grant of SKIMS, Srinagar India, under Order No. SIMS/ACAD/608 of 2019.

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Author notes

  1. Tahseen Bilal Rather and Kulsum Akhtar have contributed equally as 3rd author.

Authors and Affiliations

  1. Department of Clinical Biochemistry, SKIMS, Srinagar, 190011, India

    Gowhar Rashid, Gulzar A. Bhat, Tahseen Bilal Rather, Kulsum Akhtar, Ishrat Parveiz & Syed Mudassar

  2. Department of Medical Lab Technology, Amity Medical School, Amity University, Gurugram, Haryana, India

    Gowhar Rashid

  3. Department of Medical Oncology, SKIMS, Srinagar, India

    Syed Nisar Ahmad

  4. Department of Radiation Oncology, SKIMS, Srinagar, India

    Malik Tariq Rasool

  5. Department of Hospital Administration, SKIMS, Srinagar, India

    Farooq Ahmad Jan

  6. The Medical Research Division, Department of Internal Medicine, The National Research Centre, Cairo, Egypt

    Wael Hafez

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Contributions

GR, has done the main experimental work and played a role in designing the study as well as drafting the manuscript; GAB, revised the manuscript; TBR, KA and IP helped in data collection and methodology design; SNA, MTR and FAJ provided access for sample and data collection; AAM and WH helped in data analysis; SM, gave the concept and designed the study. She also provided all the Laboratory support required in accomplishing the study.

Corresponding author

Correspondence to Syed Mudassar.

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Ethical approval

Prior to the blood sample collection, written consent was taken from all the patients and they were also apprised about the ongoing study which was approved by the Ethical Clearance Committee of SKIMS (SIMS 1131/IEC-SKIMS/2021–06).

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Rashid, G., Bhat, G.A., Rather, T.B. et al. Assessing Colorectal Cancer Susceptibility in Kashmir, India: Insights from Xenobiotic Metabolism Gene Variants and Family Cancer History—A Comprehensive Case–Control Study. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-024-01196-x

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