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Background: Multiple studies have suggested that subjects with glutathione S-transferase P1 (GSTP1)-mutations are at high risk for urinary bladder cancer (UBC).
Methods: In the present study, we evaluated the mutations in GSTP1 and mitochondrial D-loop genes in two unrelated familial bladder cancer patients belonging to Karbi Anglong Assam tribe. Mitochondrial D-loop and nuclear GSTP1 polymorphic region were amplified and sequenced for all the family members and patients. Two SNPs in the GSTP1 gene for amino acid substitutions at codons 105 (Ile →Val) and 114 (Val →Ala) were genotyped by PCR-RFLP-based methods.
Results: mtDNA D-loop sequence variations were found and there were A and C insertions common at positions 235 and 309, respectively for both the families. Two sequence differences were identified in urinary bladder cancer samples in GSTP1 gene. These two heteroplasmic mutations were found at positions 11qG3037G/A and 11qC3038C/A in patient, father, mother, brother and son, but not in the sister and wife samples in family 2. The GSTP1, 105Ile >Val is most susceptible to inherited UBC risk for these ethnic families. The samples from families 1 and 2, including healthy subjects were placed in macrohaplogroup L3e, except the wife (macrohaplogroup F1c1a) of patient in family 1, and the wife and son (haplogroup M) of the patient in family-2.
Conclusion: A strong familial nuclear GSTP1 sequence variation and mitochondrial control region was observed in this study for familial urinary bladder cancer. This could afford early recognition of patients at risk of developing micro- or macroscopic, pathological lesions as well as the introduction of preventive measures for familial bladder cancer.
Keywords: Glutathione S-transferase; Urinary bladder cancer; mtDNA D-loop; Karbi-Anglong; Haplogroup; Heteroplasmy