Pancreas cancer predisposition: role of genes XRCC1, XRCC3 and CYP1A1 polymorphisms

Background: An individual predisposition to cancer might be searched in polymorphisms of genes involved in DNA repair, as X-Ray Cross-Complementing (XRCCs), or involved in carcinogens activation, as Cytochrome p450 (CYP1A1). Our aims were to: 1. ascertain whether there was any association between the XRCC1+22163 C/T (Arg194Trp), XRCC1+24011 G/A (Arg399Gln), XRCC3+16064 C/T (Thr241Met) or CYP1A1+4889 A/G (Ile462Val) polymorphisms and pancreatic cancer; 2. verify any correlation between the serum levels of vitamins A and E and cancer diagnosis, staging, grading and survival. Patients and Methods: We studied 91 pancreatic cancer patients (CP) and 29 with chronic pancreatitis ( PC). Survival was available for 44 CP. The genetic polymorphisms were analysed by RFLP. Serum vitamins A and E were measured by an HPLC procedure. Results: XRCC1+22163 C/T, XRCC1+24011 G/A, XRCC3+16064 C/T and CYP1A1+4889 A/G were not correlated with diagnosis. None polymorphism was correlated with tumor stage, tumor grade, or the onset of metastases after surgery. Survival was influenced only by stage (Log rank=12.4, p<0.01). In patients with less, not in those with more than 60 yrs, XRCC1+22163 CT was significantly correlated with CP (Fisher's exact test: p<0.05). On the contrary the genotype XRCC+22163 CC/XRCC+24011 AA was less frequently detected in patients with CP respect finding in patients with PC (Fisher's exact test: p<0.01). Vitamins A and E levels did not significantly differ between CP and PC. Vitamin A was significantly lower in stage III-IV (556 +/- 53 nmol/L, mean +/- SE) than stage I-II CP (896 +/- 112)(t=3.08, p<0.01). The lowest serum levels of vitamin E were in CP patients who developed liver or local metastases after surgery ( 10.71 +/- 1.4 umol/L, mean +/- SE), with respect to those who developed lung metastases (22.2 +/- 2.9)(F=8.41, p<0.01). Conclusions: XRCC1+22163 CT genotype seems involved in favouring CP in subjects with less than 60 yrs; XRCC+22163 CC/XRCC+24011 AA genotype seems to be a protective factor for CP development. These effects might be consequent to an altered protein efficiency in DNA repair. Finaly, the antioxidant vitamins A and E might partly counteract tumor growth and spread.