Journal
FAMILIAL CANCER
Volume 15, Issue 2, Pages 201-214Publisher
SPRINGER
DOI: 10.1007/s10689-015-9849-1
Keywords
Xenobiotic metabolizing pathway; CYP1A1; GSTP1; Breast cancer; Mutations; SSCP
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In first part of this study, a systematic review was designed to explore the involvement of CYP1A1 and GSTP1 genes in breast cancerogenesis. Based on systematic review, we designed a study to screen CYP1A1 and GSTP1 genes for mutation and their possible association with breast carcinogenesis. A total of 400 individuals were collected and analyzed by PCR-SSCP. After sequence analysis of coding region of CYP1A1 we identified eleven mutations in different exons of respective gene. Among these eleven mutations, similar to 3 folds increased breast cancer risk was found associated with Asp82Glu mutation (OR 2.99; 95 % CI 1.26-7.09), with Ser83Thr mutation (OR 2.99; 95 % CI 1.26-7.09) and with Glu86Ala mutation (OR 3.18; 95 % CI 1.27-7.93) in cancer patients compared to controls. Furthermore, similar to 4 folds increase in breast cancer risk was found associated with Asp347Glu, Phe398Tyr and 5178delT mutations (OR 3.92; 95 % CI 1.35-11.3) in patients compared to controls. The sequence analysis of GSTP1 resulted in identification of total five mutations. Among these five mutations, similar to 3 folds increase in breast cancer risk was observed associated with 1860G>A mutation, with 1861-1876delCAGCCCTCTGGAGTGG mutation (OR 2.70; 95 % CI 1.10-6.62) and with 1861C>A mutation (OR 2.97; 95 % CI 1.01-8.45) in cancer patients compared to controls. Furthermore, similar to 5 folds increase in breast cancer risk was associated with 1883G>T mutation (OR 4.75; 95 % CI 1.46-15.3) and similar to 6 folds increase in breast cancer risk was found associated with Iso105Val mutation (OR 6.43; 95 % CI 1.41-29.3) in cancer patients compared to controls. Our finding, based on systematic review and experimental data suggest that the polymorphic CYP1A1 and GSTP1 genes may contribute to risk of developing breast cancer.
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