Linkage disequilibrium and haplotypes of five TP53 polymorphisms in oesophageal cancer patients

The aim of present study was to evaluate the linkage disequilibrium (LD) of p.R72P, PIN3 Ins16bp, p.P47S, p.R213R and r.13494g[a polymorphism of TP53 and their haplotypes association with oesophageal cancer risk in patients from Punjab, northwest India. A total of 466 samples, including 233 oesophageal cancer patients and 233 healthy individuals were analysed. Data analysis revealed the gender specific association. In female group, arginine–proline (RP) genotype (P = 0.08) and P allele (P = 0.07) of p.R72P polymorphism was marginally associated with increased risk of oesophageal cancer. A1A2 genotype (P = 0.06) and A2 allele (P = 0.07) of PIN3 Ins16bp polymorphism was marginally associated with decreased risk of oesophageal cancer in male group. A1A2–GA genotype combination (P = 0.04) of PIN3 and r.13494g[a polymorphisms was significantly associated with decreased risk of oesophageal cancer in male group. In female group, PP–GA genotype combination (P = 0.02) of p.R72P and r.13494g[a polymorphisms and RP–A1A1–GG genotype combination (P = 0.04) of p.R72P, PIN3 and r.13494g[a polymorphisms was significantly associated with increased risk of oesophageal cancer. We observed moderate LD between two intronic polymorphisms PIN3 Ins16bp and r.13494g[a (D0 = 0.90; r 2 = 0.68). Haplotype analysis revealed that none of the haplotype combination was associated with oesophageal cancer risk when both the genders were considered. Stratification on the basis of gender showed that P-A2-P-A-A haplotype of p.R72P, PIN3 Ins16bp, p.P47S, p.R213R and r.13494g[a polymorphisms was marginally associated with reduced oesophageal cancer risk in male group (P = 0.08). Replication of these findings in independent cohorts may be insightful for the role of TP53 in oesophageal cancer pathogenesis.

Chromosomal instability in the lymphocytes of breast cancer patients.

Genomic instability in the tumor tissue has been correlated with tumor progression. In the present study, chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) of breast tumor patients were studied to assess whether chromosomal instability (CIN) in PBLs correlates with aggressiveness of breast tumor (i.e., disease stage) and has any prognostic utility. Cultured blood lymphocyte metaphases were scored for aberrations in 31 breast cancer patients and 20 healthy age and sex-matched controls. A variety of CAs, including aneuploidy, polyploidy, terminal deletions, acentric fragments, double minutes, chromatid separations, ring chromosome, marker chromosome, chromatid gaps, and breaks were seen in PBLs of the patients. The CAs in patients were higher than in controls. A comparison of the frequency of metaphases with aberrations by grouping the patients according to the stage of advancement of disease did not reveal any consistent pattern of variation in lymphocytic CIN. Neither was any specific chromosomal abnormality found to be associated with the stage of cancer. This might be indicative of the fact that cancer patients have constitutional CIN, which predisposes them to the disease, and this inherent difference in the level of genomic instability might play a role in disease progression and response to treatment.

SCE Analysis In Treated And Unteated Leprosy Patients.

Spontaneow sister chromatid exchange (SCE) frequency was studied in fifteen leprosy patients and twelve age matched controls. The mean SCH/cell was 10.23 + 4.1 in controls. The three untreated patients had mean SCE/cell value of 20.3 + 1.41. Among patients under treatment, five patients in initial stage of disease and treatment duration between one to nine months, the mean SCE/cell value was 29.78 + 4.244. In the seven patients with advanced stage of disease and treatment duration between 20 to 50 months, the mean SCE/cell value was 31.87 + 7.31. The results indicate a clastogenic effect of leprosy on peripheral leucocytes, which was increased due to anti-leprosy treatment.