SULT1A1 rs9282861 polymorphism-a potential modifier of efficacy of the systemic adjuvant therapy in breast cancer?
BACKGROUND
Sulfotransferase 1A1 (SULT1A1) participates in the elimination of 4-hydroxy-tamoxifen (4-OH-TAM), which is one of the major active metabolites of tamoxifen (TAM). Homozygous SULT1A1 variant allele genotype has been associated with lower catalytic activity and thermostability of the enzyme. Previous clinical studies suggest that the SULT1A1 rs9282861 polymorphism may influence the survival of breast cancer patients treated with TAM in the adjuvant setting. We investigated the effect of rs9282861 genotypes on the survival of Finnish breast cancer patients treated with adjuvant chemotherapy or TAM.


METHODS
The rs9282861 genotypes of 412 Finnish breast cancer patients with early breast cancer were identified by using PCR-RFLP method. Seventy six patients were treated with adjuvant cyclophosphamide based chemotherapy only, 65 patients received adjuvant TAM, and four patients were treated with both adjuvant chemotherapy and TAM. Overall long-term survival (OS), breast cancer specific survival (BCSS), and relapse-free survival (RFS) by rs9282861 genotypes were evaluated by the Kaplan-Meier method and Cox regression analysis.


RESULTS
The multivariate analysis of 145 patients receiving either adjuvant TAM or chemotherapy showed a statistically significantly improved OS in patients with the rs9282861 homozygous variant AA genotype (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.29-0.88, P = 0.015). In the separate analyses of patients receiving only chemotherapy or adjuvant TAM, there were no statistically significant differences in survival.


CONCLUSIONS
In this prospective study, we observed a previously unreported association between the SULT1A1 rs9282861 genotype and OS of breast cancer patients treated with adjuvant chemotherapy or TAM. This novel finding suggests that the rs9282861 polymorphism modifies the long-term clinical outcome of patients receiving adjuvant TAM or chemotherapy.
Cancer Center, Kuopio University Hospital, P,O,BOX 1777, 70211 Kuopio, Finland. maria.tengstrom@kuh.fi
Maria
M
Tengström
Arto
A
Mannermaa
Veli-Matti
VM
Kosma
Ari
A
Hirvonen
Vesa
V
Kataja
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015239:Arylsulfotransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D055815:Young Adult
D000970:Antineoplastic Agents; D013629:Tamoxifen; D003520:Cyclophosphamide; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human