This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane‐ and cisplatin‐treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first‐line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP‐binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S‐transferase M1 (GSTM1), glutathione S‐transferase P1 (GSTP1), glutathione S‐transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X‐ray Cross Complementing group 3 (XRCC3), X‐ray Cross Complementing group 4 (XRCC4), X‐ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5‐fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 ± 0.19 months and 11.9 ± 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20–0.92; P = 0.03) and progression‐free survival (HR = 0.51; 95% CI, 0.26–1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11–2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane‐ and cisplatin‐treated patients.(Cancer Sci 2010; 101: 1247–1254)

Summary: Polymorphisms in the genes coding folate‐metabolizing enzymes affect the risk of some forms of cancer. We investigated the association between these polymorphisms and non‐Hodgkin lymphoma (NHL) risk in a population‐based study (583 cases and 1700 controls). The MTHFR 677TT and CT genotypes were associated with reduced risk for NHL [odds ratios (OR) = 0·79; 95% confidence intervals (CI) = 0·65–0·98 for 677CT and 0·61; 0·45–0·82 for 677TT] and diffuse large B‐cell lymphoma (DLBCL) (OR = 0·68; 0·51–0·88 for 677CT; OR = 0·56; 0·38–0·83 for 677TT). The MTHFR 1298CC genotype was associated with increased risk for NHL (OR = 1·71; 1·07–2·75) and T‐cell lymphoma (OR = 3·05; 1·53‐6·11). The MTRR 66GG genotype was associated with increased risk for DLBCL (OR = 1·56; 1·03‐2·38) and the TYMS 2R2R genotype was associated with increased risk for T‐cell lymphoma (OR = 2·83; 1·33–6·01). Using subjects with 3RG3RG as a reference group, TYMS 2R2R was associated with increased risk for T‐cell lymphoma (OR = 2·46; 1·04–5·79). Interestingly, we observed a reduced association between the TYMS 2R3RG genotype and DLBCL (OR = 0·61; 0·38–0·99). These results suggest that MTHFR, MTRR and TYMS polymorphisms may play a significant role in the risk for NHL.