Predictive assessment in pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy

Published data have shown inconsistent results about the pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy. This meta-analysis aimed to summarize published findings and provide more reliable association. A total of 53 eligible studies including 7433 patients were included. Patients bearing the favorable TrpTrp and TrpArg genotypes of Arg194Trp were more likely to better response rates to platinum-based chemotherapy compared to those with the unfavorable ArgArg genotype (TrpTrp+TrpArg vs. ArgArg: odds ratio (OR) = 2.02, 95% CI, 1.66–2.45). The GlnGln and GlnArg genotypes of Arg399Gln were significantly associated with the poorer response rates compared to those with the ArgArg genotype (GlnGln +GlnArg vs. ArgArg: OR = 0.68, 95% CI, 0.54–0.86). The GlnGln genotype might be more closely associated with shorter survival time and higher risks of death for patients (GlnGln vs. ArgArg: hazard ratio (HR) = 1.14, 95% CI, 0.75–1.75). Our cumulative meta-analyses indicated a distinct apparent trend toward a better response rate for Arg194Trp, but a poorer response rate in Arg399Gln. These findings indicate a predictive role of XRCC1 polymorphisms in clinical outcomes. The use of XRCC1 polymorphisms as predictive factor of clinical outcomes in personalized chemotherapy treatment requires further verification from large well-designed pharmacogenetics studies.


Predictive assessment in pharmacogenetics of
Note: OR: odds ratio; SE: standard error; Horizontal line represents mean effect size. Log OR stands for natural logarithm of OR. Log OR is plotted versus SE of Log OR for each enrolled study. Each circle point stands for a separate study for the indicated association between the XRCC1 Arg194Trp polymorphism and clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy. Note: OR: odds ratio; SE: standard error; Horizontal line represents mean effect size. Log OR stands for natural logarithm of OR. Log OR is plotted versus SE of Log OR for each enrolled study. Each circle point stands for a separate study for the indicated association between the XRCC1 Arg399Gln polymorphism and clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy.

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

P16
Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

P16-18
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

P16-18
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

P16-18
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).
P16-18, Figure  1,S3 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

P16-18,Figure1,S3
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.
P18, Figure S1,S2 Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). P18 Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

Section/topic # Checklist item Reported on page #
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.
P2-7, Figure  1,S3 Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. P2-7, Table 1, 2 Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). P2-13, Figure  S1,S2 Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

P13-16
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

P16
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. For more information, visit: www.prisma-statement.org.
Page 2 of 2