***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer . We attempted to determine whether single nucleotide polymorphisms in ERCC1 , GST , TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy .  Total genomic DNA was extracted from the whole blood of patients . The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1 , GST , TS and UGT1A1 . The response rate of FOLFOX  ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16 % , respectively . TTP and OS of first-line administration of FOLFOX ( N=35 ) were 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) , respectively . Only the GSTM1 positive genotype exhibited a significantly better time to progression ( P=0.023 ) . However , significant genotypic variation of TS , GST and ERCC1 , which was assumed to affect the activity of oxaliplatin , was not observed to affect RR , toxicity and overall survival . The response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed in 55.4 and 9.5 % of cases , respectively . TTP and OS of first-line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5 months ) . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia . However , significant genotypic variation of UGT1A1 , which was assumed to affect irinotecan toxicity , was not observed to affect RR , toxicity or survival . In this study , the GSTM1 positive genotype evidence d a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI The discovery of pharmacogenomic markers in colorectal cancer ( CRC ) could be setting -specific . FOLFOX4 is employed in the adjuvant and metastatic setting in CRC . This prospect i ve study is aim ed to vali date in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting ( that is , GSTP1-rs947894 , and -rs1138272 ; GSTM1-null genotype ; AGXT-rs4426527 , -rs34116584 and del-74 bp ) , and to discover additional markers . CRC patients ( n=144 ) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes .  Grade ⩾2 neurotoxicity was associated ( false discovery rate-adjusted q-value < 0.1 ) with single-nucleotide polymorphisms in ABCC1 ( rs2074087 : odds ratio=0.43(0.22–0.86 ) ) , and ABCC2 ( rs3740066 : 2.99(1.16–7.70 ) ; rs1885301 : 3.06(1.35–6.92 ) ; rs4148396 : 4.69(1.60–13.74 ) ; rs717620 : 14.39(1.63–127.02 ) ) . hMSH6-rs3136228 was associated with grade 3–4 neutropenia ( 3.23(1.38–7.57 ) , q-value=0.0937 ) . XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity ( 8.90(2.48–31.97 ) , q-value=0.0150 ) . The markers previously identified in metastatic CRC were not vali date d. We have identified new markers of toxicity in genes of transport and DNA repair . If vali date d in other studies , they could help to identify patients at risk of toxicity Purpose The aim of this study was to assess whether genetic polymorphisms in p53 , glutathione S-transferase P1 ( GSTP1 ) , GSTM1 , excision repair cross complementing group 1 ( ERCC1 ) and X-ray repair cross-complementing group 1 ( XRCC1 ) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy .  Methods The genetic polymorphisms in p53 , GSTP1,GSTM1 ( null ) , ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method .  Results Among the five studied polymorphisms , p53 codon 72 Pro/Pro , GSTP1 codon 105 Ile/Ile , and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival ( P < 0.05 ) ; and the prognostic effect was retained in the Cox multivariate analysis . Combination analysis with the three polymorphisms using the Kaplan – Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes ( P < 0.05 ) . No significant association was found between the GSTM1 ( null ) or the ERCC1 codon 118 genotypes and the clinical outcome ( P > 0.05 ) . Conclusion Testing for p53 Arg72Pro , GSTP1 Ile105Val , and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy . Selecting specific adjuvant treatments according to the individual genetic background may represent an innovative strategy that warrants prospect i ve studies Purpose : To explore the effect of dihydropyrimidine dehydrogenase ( DPD ) single nucleotide polymorphisms ( SNP ) and haplotypes on outcome of capecitabine . Experimental Design : Germline DNA was available from 568 previously untreated patients with advanced colorectal cancer participating in the CAIRO2 trial , assigned to capecitabine , oxaliplatin , and bevacizumab ± cetuximab . The coding region of dihydropyrimidine dehydrogenase gene ( DPYD ) was sequenced in 45 cases with grade 3 or more capecitabine-related toxicity and in 100 r and omly selected controls ( cohort ) . Most discriminating ( P < 0.1 ) or frequently occurring ( > 1 % ) nonsynonymous SNPs were analyzed in all 568 patients .  SNPs and haplotypes were associated with toxicity , capecitabine dose modifications , and survival . Results : A total of 29 SNPs were detected in the case – cohort analysis , of which 8 were analyzed in all 568 patients . Of the patients polymorphic for DPYD IVS14 + 1G > A , 2846A > T , and 1236G > A , 71 % ( 5 of 7 ) , 63 % ( 5 of 8) , and 50 % ( 14 of 28 ) developed grade 3 to 4 diarrhea , respectively , compared with 24 % in the overall population . All patients polymorphic for IVS14 + 1G > A developed any grade 3 to 4 toxicity , including one possibly capecitabine-related  death . Because of toxicity , a mean capecitabine dose reduction of 50 % was applied in IVS14 + 1G > A and 25 % in 2846A > T variant allele carriers . Patients were categorized into six haplotype groups : one predicted for reduced ( 10 % ) , and two for increased risks ( 41 % and 33 % ) for severe diarrhea . Individual SNPs were not associated with overall survival , whereas one haplotype was associated with overall survival [ HR ( 95 % CI ) = 0.57 ( 0.35–0.95 ) ] . Conclusions : DPYD IVS14 + 1G > A and 2846A > T predict for severe toxicity to capecitabine , for which patients require dose reductions . Haplotypes assist in selecting patients at risk for toxicity to capecitabine . Clin Cancer Res ; 17(10 ) ; 3455–68 . © 2011 AACR PURPOSE The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin , folinic acid , and fluorouracil palliative chemotherapy .  MATERIAL S AND METHODS Consecutive patients were prospect ively enrolled onto medical oncology units in Central Italy . Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion . Peripheral blood sample s were used for genotyping 12 polymorphisms in thymidylate synthase , methylenetetrahydrofolate reductase , xeroderma pigmentosum group D ( XPD ) , excision repair cross complementing group 1 ( ERCC1 ) , x-ray cross complementing group 1 , x-ray cross complementing protein 3 , glutathione S-transferases ( GSTs ) genes . The primary end point of the study was to investigate the association between genotypes and progression-free survival ( PFS ) . RESULTS In 166 patients , ERCC1 - 118 T/T , XPD-751 A/C , and XPD-751 C/C genotypes were independently associated with adverse PFS . The presence of two risk genotypes ( ERCC1 - 118 T/T combined with either XPD-751 A/C or XPD-751 C/C ) occurred in 50 patients ( 31 % ) . This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84 % and 95 % CI of 1.47 to 5.45 ( P = .002 ) . Neurotoxicity was significantly associated with GSTP1 - 105 A/G. Carriers of the GSTP1 - 105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1 - 105 A/G and GSTP1 - 105 A/A genotypes . CONCLUSION A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer . These findings deserve confirmation in additional prospect i ve studies PURPOSE To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Peripheral blood sample s from 175 prospect ively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy  were used for genotyping 13 polymorphisms in nine genes ( TS , MTHFR , XPD , ERCC1 , XRCC1 , XRCC3 , GSTPI , GSTTI , GSTMI ) . Genotypes were correlated to response and survival . RESULTS The overall response rate was 41 % , the median progression-free survival ( PFS ) was 24 weeks ( range , 4 to 50 weeks ) , and the median overall survival ( OS ) was 39 weeks ( range , 8 to 72 + weeks ) . Chemoresistance and poor survival were significantly associated with TS 5'-UTR 3G-genotype ( 2R/3 G , 3C/3 G , 3G/3 G ) and GSTP1 105 A/A homozygous genotype . Sixty-one patients ( 35 % ) did not show any of these risk genotypes ( group 0 ) , 57 patients ( 32.5 % ) showed one of the two risk genotypes ( group 1 ) , and 57 patients ( 32.5 % ) showed both risk genotypes ( group 2 ) . Median PFS and OS in group 0 patients were 32 weeks ( range , 8 to 50 weeks ) and 49 weeks ( range , 18 to 72 + weeks ) , respectively . Group 1 and group 2 patients showed significantly worse PFS ( median , 26 weeks [ range , 6 to 44 weeks ] and 14 weeks [ range , 4 to 38 weeks ] , respectively ) and worse OS ( median , 39 weeks [ range , 10 to 58 weeks ] and 28 weeks [ range , 8 to 56 weeks ] ) , respectively , than group 0 patients . This adverse effect was retained in multivariate analysis . CONCLUSION Specific polymorphisms may influence clinical outcomes of AGC patients . Selecting palliative chemotherapy on the basis 
    Output:
    
Subgroup analyses suggested that neurotoxicity was associated with GSTM1 polymorphism in the Asian population , neutropenia was associated with GSTM1 polymorphism in palliative chemotherapy and older patients ( mean age > 60 years ) , and tumor response was associated with GSTT1 polymorphism in gastric cancer and responders defined by complete and partial responses .