***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: Polymorphisms of glutathione S-transferase ( GST ) enzymes have been correlated with altered risk of several cancers , as well as altered response and toxicity from cancer chemotherapy . We report a low cost , highly reproducible and specific PCR-based high-throughput assay for genotyping different GSTs design ed for use in large clinical trials . In comparison to an alternative genotyping method ( single nucleotide extension ) , the sensitivity and specificity of the high throughput assay was shown to be 92 and 97 % , respectively , depending on the source of genomic DNA . Using the high-throughput assay , we demonstrate by multivariate analysis an increased risk of acute lymphoblastic leukemia , glial brain tumors , and osteosarcoma for patients carrying nonnull alleles of GSTM1 and /or GSTT1 Abstract — A model for childhood leukemia proposes that characteristic chromosomal translocations can arise in utero and that for most cases a second hit occurring postnatally will be necessary . Possible causal mechanisms for leukemias are environmental factors such as ionizing radiation from x rays and inherited susceptibility from polymorphisms in DNA repair genes . We performed a case-control study of childhood acute lymphoblastic leukemia measuring reported postnatal x rays in 701 cases aged 0–14 y and in as many population -based controls matched on age and sex . In addition we performed a case-only study in 207 cases to evaluate the interaction between x ray exposure and polymorphisms in DNA repair genes . There was an increase in risk of leukemia with number of x rays : the adjusted odds ratio for two or more x rays vs. none was 1.48 ( 95 % confidence interval : 1.11–1.97 ) . That risk was slightly higher among girls ( odds ratio = 1.67 ) . A polymorphism in the APE gene ( ex 5 ) involved in the base excision repair system was suggestive of an increased risk among boys and a reduced risk among girls . HMLH1 ( ex 8) , a mismatch repair gene , was associated with reduction of risk among girls . Results from the genetic data are still preliminary and must be interpreted with caution especially because of the relatively small number of genotyped cases . However , ionizing radiation from x rays as well as polymorphisms in DNA repair genes are plausible risk factors for childhood leukemia and should be studied more The aldo-keto reductase 1C3 ( AKR1C3 ) gene located on chromosome 10p15-p14 , a regulator of myeloid cell proliferation and differentiation , represents an important c and i date gene for study ing human carcinogenesis . In a prospect ively enrolled population -based case-control study of Han Chinese conducted in Kaohsiung in southern Taiwan , a total of 114 leukemia cases and 221 controls < 20 years old were recruited between November 1997 and December 2005 . The present study set out to evaluate the association between childhood leukemia and both maternal and offspring 's genotypes . To do so , we conducted a systematic assessment of common single-nucleotide polymorphisms ( SNPs ) at the 5 ' flanking 10 kb to 3 ' UTR of AKR1C3 gene . Gln5His and three tagSNPs ( rs2245191 , rs10508293 and rs3209896 ) and one multimarker ( rs2245191 , rs10508293 and rs3209896 ) were selected with average 90 % coverage of untagged SNPs by using the HapMap II data set . Odds ratios and 95 % confidence intervals were adjusted for age and gender . After correcting for multiple comparisons , we observed that risk of developing childhood leukemia is significantly associated with rs10508293 polymorphism on intron 4 of the AKR1C3 gene in both offspring alone and in the combined maternal and offspring genotypes ( nominal P < 0.0001 , permutation P < 0.005 ) . The maternal methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect modifier of the maternal intron 4 polymorphism of the AKR1C3 gene ( rs10508293 ) and the childhood leukemia risk . In conclusion , this study suggests that AKR1C3 polymorphisms may be important predictive markers for childhood leukemia susceptibility 
    Output:
    
The collected evidence suggests that genetic polymorphisms in CYP2E1 , GSTM1 , NQO1 , NAT2 , MDR1 , and XRCC1 are capable of modulating leukaemia risk , mainly when associated with environmental exposures , such as domestic pesticides and insecticides , smoking , trihalomethanes , alcohol consumption , and x-rays .
More recently , genome wide association studies identified significant associations between genetic polymorphisms in ARID5B e IKZF1 and acute lymphoblastic leukaemia , but only a few studies have replicated these results until now .
In conclusion , genetic susceptibility contributes to the risk of childhood leukaemia through the effects of gene-gene and gene-environment interactions