X-Ray Cross-Complementing 1 gene polymorphisms, not X-Ray Cross-Complementing 3 or cytochrome P450, might predispose to pancreatic cancer

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 XRCC122163 C/T (Arg194Trp), XRCC124011 G/A (Arg399Gln), XRCC316064 C/T (Thr241Met) or CYP1A14889 A/G (Ile462Val) polymorphisms and PC; (2) verify any correlation between the serum levels of vitamins A and E and PC cancer diagnosis, staging, grading and survival. Patients and Methods: We studied 91 PC patients and 29 chronic pancreatitis (CP). Survival was available for 44 PC. The genetic polymorphisms were analysed by RFLP. Serum vitamins A and E were measured by an HPLC procedure. Results: XRCC122163 C/T, XRCC316064 C/T and CYP1A14889 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, XRCC122163 CT was significantly correlated with PC (Fisher’s exact test: p 0.05). Vitamins A and E levels did not significantly differ between PC and CP. Vitamin A was significantly lower in stage III-IV (556 53 nmol/L, mean SE) than stage I-II PC (896 112)(t 3.08, p 0.01). The lowest serum levels of vitamin E were in PC 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: XRCC122163 CT genotype seems involved in favouring PC in subjects with less than 60 yrs; these effects might be consequent to an altered protein efficiency in DNA repair; the antioxidant vitamins A and E might partly counteract tumor growth and spread.