Interaction between lifestyle factors and the XRCC1, XPD, and XRCC3 genetic variations modulates the risk for sporadic colorectal cancer

Background: Genetic variations, such as those affecting DNA repair genes, could represent susceptibility factors for sporadic colorectal cancer (CRC) as a result of their interaction with environmental factors. Materials and

methods: 80 female and 70 males patients diagnosed with sporadic CRC in the Surgical Clinic III Cluj were genotyped for Arg399Gln-XRCC1, Lys751Gln-XPD and Met241Thr-XRCC3 using PCR-RFLP methods. We also genotyped 100 females and 62 males, who formed the control group. Genotyping results were related to environmental risk factors, smoking habit and diet. Results: Male patients carriers of the Arg399Gln, Lys751Gln, Met241Thr had a 4.09 (95%CI[0.96-19.98],p=0.05)-fold, 5.95(95%CI[1.08-43.22],p=0.03)-fold and 3.73(95%CI[0.86- 18.53],p=0.05)- fold significantly increased risk to develop sporadic CRC if they smoked. A significantly increased risk for CRC was observed in females and males with high daily fried red meat intake, carriers of the Arg399Gln (OR 2.77 95%CI [1.34-6.82],p=0.015 and OR 8.64 95%CI[2.67-29.14],p<0.001), Lys751Gln (OR 4.12 95%CI[1.37-12.74],p=0.007 and OR 5.06 95%CI[1.4-19.02],p=0.006), Met241Thr (OR5.92 95%CI[2.21- 16.23],p<0.001 and OR 5.64 95%CI[1.52-21.7],p=0.022). Female patients with high fried red meat intake had a significantly higher risk to develop early-onset sporadic CRC if they were carriers of the Arg399Gln-XRCC1 (OR 5.14 95%CI[0.99-28.3],p=0.047), Thr241Met-XRCC3 (OR 6.67 95%CI[1.05-46.67],p=0.025) and Lys- 751Gln-XPD (OR 4.7 95%CI[0.99-23.32],p=0.034). Conclusions: In Romanians, the association between the mutated genotypes and environmental risk factors modulates the risk for sporadic CRC. Smoking in association with the Arg399Gln-XRCC1 genetic variation influences the early onset of sporadic colorectal cancer in females. Diet rich in fried red meat intake associated with Arg399Gln-XRCC1, Lys751Gln-XPD and Thr241Met- XRCC3 genetic variations significantly influences the early onset of sporadic colorectal cancer in females.