[Association of murine double minute 2 and P53 polymorphisms with breast cancer susceptibility].

OBJECTIVE: To investigate the combined effects between the two polymorphisms murine double minute 2 (MDM2) rs2279744 T→G and P53 rs1042522 G→C on the genetic susceptibility of breast cancer. METHODS: A total of 600 female patients with diagnosed breast cancer were consecutively recruited from the Yuhang district, Hangzhou city during March 2001 to May 2009. In the same period as the cases were collected, 600 healthy women living in Yuhang district, Hangzhou city were selected from a nutritional survey conducted. Peripheral blood lymphocytes were obtained from the study subjects and the demographic information were collected through questionnaires. PCR-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping MDM2 rs2279744 T→G and P53 rs1042522 G→C. Logistic regression analysis was used to analyze the combined effects of the two polymorphisms on breast cancer risk. RESULTS: The frequency of MDM2 rs2279744 GG, TG and TT genotypes were 31.5% (189/600), 45.5% (273/600), 23.0% (138/600) in case group and 19.0% (114/600), 49.2% (295/600), 31.8% (191/600) in control group. The frequency of P53 rs1042522 GG, GC and CC genotypes were 23.1% (139/600), 50.2% (301/600), 26.7% (160/600) in case group and 30.5% (183/600), 51.3% (308/600), 18.2% (109/600) in control group. Logistic regression analysis showed that carriers with rs2279744 TG, GG genotypes had a significant increased risk for developing breast cancer compared with rs2279744 TT carriers (OR = 1.31, 95%CI: 0.97 - 1.73 for TG; OR = 2.24, 95%CI: 1.61 - 3.09 for GG). When comparing with rs1042522 GG carriers, carriers with rs1042522 GC, CC genotypes had a significant increased risk for developing breast cancer (OR = 1.34, 95%CI: 0.94 - 1.68 for GC; OR = 1.89, 95%CI: 1.35 - 2.68 for CC). The united analysis of this two polymorphisms showed that compared with individuals carrying rs2279744 TT and rs1042522 GG (the frequency were 4.8% (29/600) in case group and 11.5% (69/600) in control group), carries with rs2279744 TG/GG and rs1042522 GC/GG genotypes (the frequency were 95.2% (571/600) in case group and 88.5% (531/600) in control group) showed significant higher risk in the susceptibility to breast cancer (OR = 2.30, 95%CI: 1.39 - 3.82 for TG/GC + GG; OR = 2.14, 95%CI: 1.29 - 3.55 for TT + GC/CC; OR = 2.86, 95%CI: 1.80 - 4.53 for TG/GG + GC/CC). The combination of MDM2 rs2279744 T→G and P53 rs1042522 G→C contributed to a significantly higher risk of breast cancer than did any one of the variant (P = 0.046). The risk of susceptibility to breast cancer was much higher when this two polymorphisms both variant. CONCLUSIONS: The MDM2 rs2279744 T→G and P53 rs1042522 G→C may be risk factor for breast cancer. Significant combined effects between the two polymorphisms may contribute to the genetic susceptibility to breast cancer.

Lamivudine prophylaxis reduces the incidence and severity of hepatitis in hepatitis B virus carriers who receive chemotherapy for lymphoma.

BACKGROUND: Hepatitis B virus (HBV) infection is a common disease in China. Severe hepatitis is a well recognized complication in HBV carriers with malignant disease who receive cytotoxic chemotherapy. The objective of the current study was to assess the value of antiviral lamivudine for reducing the incidence and severity of hepatitis in HBV carriers with lymphoma who receive chemotherapy. METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group was comprised of 40 patients who received oral lamivudine at a dose of 100 mg daily before and until at least 8 weeks after they discontinued chemotherapy. The historic control group was comprised of 116 patients who received chemotherapy without lamivudine. The incidence and severity of hepatitis and other adverse clinical outcomes were compared between the two groups. Significant prognostic factors for the development of hepatitis were determined based on data derived from the control group. RESULTS: The two groups were comparable in most clinical baseline characteristics, including gender distribution, age, tumor types, primary treatment, hepatitis Be antigen status, and the use of anthracyclines or/and prednisone. In the prophylactic lamivudine group, there was significantly less incidence of hepatitis (17.5% vs. 51.7% in the control group; P = 0.000); less severe hepatitis (according to World Health Organization [WHO] criteria) (10% with Grade 1, 5% with Grade 2, and 2.5% with Grade 3 hepatitis vs. 3.4% with Grade 1, 12.1% with Grade 2, 12.9% with Grade 3, and 23.3% with Grade 4 hepatitis in the control group; P = 0.000); and less disruption of chemotherapy (10.0% vs. 37.1% in the control group; P = 0.001). The overall mortality as a result of hepatitis in the prophylactic lamivudine group was lower compared with that in the control group, but the difference was not statistically significant (0.0% vs. 5.2%; P = 0.163). In the control group, the factor associated with a greater risk of developing hepatitis was the use of prednisone. In the prophylactic lamivudine group, 1 of 40 patients (2.5%) developed hepatitis that was attributable to HBV reactivation. Further examination demonstrated that this single patient had a variation of HBV with YMDD mutations after the use of lamivudine for 9.2 months. CONCLUSIONS: The results of the current study confirmed previous reports that lamivudine prophylaxis significantly reduced the incidence and severity of hepatitis in HBV carriers who were receiving chemotherapy for lymphoma. The chemotherapy disruption rate as a result of severe hepatitis also was decreased significantly.