| Patients receiving tamoxifen have shorter recurrence-free survival |
rs3740065 is a SNP in the ATP-binding cassette, sub-family C (CFTR/MRP), member 2 ABCC2 gene.
A study of 282 hormone receptor-positive, invasive breast cancer Japanese patients receiving tamoxifen found a significant association with shorter recurrence-free survival (p = .00017; hazard ratio 10.64, CI: 1.44 - 78.88) in rs3740065(T;T) patients; the hazard ratio for carriers of one (T) allele was 3.5 (CI: 0.5-26).[PMID 20124171
] Curiously, no significant difference in plasma levels of the tamoxifen metabolites endoxifen or 4-hydroxytamoxifen were seen.
This same study of tamoxifen users concluded that rs3740065(T;T) patients who also had two CYP2D6 risk alleles had a 45 fold higher risk of recurrence than patients with zero or one (out of the possible four) risk alleles. The overall average recurrence risk was 5x for carriers of a total of two risk alleles, and 20x for carriers of a total of three risk alleles.[PMID 20124171]
A nearby SNP, rs11190303, also showed significant association to recurrence-free survival; it was shown to be strongly linked to rs3740065 (r2 with LD of 0.79).[PMID 20124171]
[PMID 23222202] Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia.
] Curiously, no significant difference in plasma levels of the tamoxifen metabolites endoxifen or 4-hydroxytamoxifen were seen.
