Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs,GSTM1,GSTT1andGSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles ofGSTM1,GSTT1, andGSTP1Ile105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients withGSTT1genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring theGSTP1IleVal or ValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the IleIle genotype. In multivariate Cox analysis, patients with theGSTP1105ValVal genotype had 3.87 more chance of presenting disease progression than those with the IleIle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related toGSTT1andGSTP1Ile105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT.

We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breast cancer. DNA from 742 sporadic breast cancer patients and 742 controls was analyzed using the polymerase chain reaction, followed by the restriction fragment length polymorphism technique. More patients had the CYP1A1 4889AG+GG genotype compared to controls (29.0% versus 23.2%, p=0.004). The G allele carriers had a 1.50-fold increased risk (95% CI: 1.14-1.97) of sporadic breast cancer compared to the other study participants. The frequency of the 4889AG+GG genotype among the Caucasian patients was higher than in the non-Caucasian patients (30.4% versus 20.2%, p=0.03) and controls (30.4% versus 23.2%, p=0.002). Caucasians and G allele carriers had a 1.61-fold increased risk (95% CI: 1.20-2.15) of sporadic breast cancer compared to other subjects. The CYP1A1 4889AG+GG genotype was more common among patients with a younger median age at first full-term pregnancy than among controls (33.8% versus 23.2%, p=0.001) and subjects whose first full-term pregnancies occurred at an older age (33.8% versus 26.1%, p=0.03). Women with the CYP1A1 4889AG+GG genotype and earlier first full-term pregnancies had a 1.87-fold (95% CI: 1.32-2.67) increased risk of sporadic breast cancer compared to the other study participants. Excess CYP1A1 4889AG+GG (39.8% versus27.1%, p=0.01) and 6235TC+CC (48.4% versus 35.9%, p=0.02) genotypes were also observed in patients with grade I and II tumors compared to patients with grade III tumors and controls (39.8% versus 23.2%, p=0.04; 48.4% versus 38.6%, p=0.04). The G and C allele carriers had a 2.44-fold (95% CI: 1.48-4.02) and 1.67-fold (95% CI: 1.03-2.69) increased risk, respectively, of developing grade I and II tumors compared to other subjects. The CYP1A1 A4889G and T6235C polymorphisms may alter the risk of sporadic breast cancer in Brazilian women.