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

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.