Dataset Information

Investigation of Cytotoxic T-lymphocyte antigen-4 polymorphisms in non-small cell lung cancer: a case-control study.

ABSTRACT: The objective of this case-control study was to extensively explore the relationship of Cytotoxic T-lymphocyte antigen-4 (CTLA-4) tagging polymorphisms with susceptibility to non-small-cell lung cancer (NSCLC). We recruited 521 sporadic NSCLC cases and 1,030 non-cancer controls. The genotypes of CTLA-4 rs16840252 C>T, rs231775 G>A, rs3087243 G>A and rs733618 T>C polymorphisms were evaluated using a custom-by-design 48-Plex SNPscan Kit. Our findings revealed there was no statistically significant difference in CTLA-4 genotypes distribution among NSCLC patients and non-cancer controls. Similar findings were observed in the logistic regression analyses. However, the stratified analyses suggested CTLA-4 rs733618 vatiants were correlated with the development of NSCLC in ? 60 years subgroup (TC vs. TT: adjusted OR = 1.45, 95% CI = 1.04-2.02, P = 0.030) and even drinking subgroup (TC vs. TT: adjusted OR = 2.27, 95% CI = 1.11-4.60, P = 0.024 and TC/CC vs. TT: adjusted OR = 2.26, 95% CI = 1.15-4.43, P = 0.018). In conclusion, the present case-control study highlights that the CTLA-4 rs733618 T>C polymorphism was associated with the development of NSCLC in ? 60 years and even drinking subgroups. A fine-mapping study with functional assessment is necessary to confirm or refute our findings.

SUBMITTER: Chen S

PROVIDER: S-EPMC5652731 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Investigation of <i>Cytotoxic T-lymphocyte antigen-4</i> polymorphisms in non-small cell lung cancer: a case-control study.

Chen Shuchen S Wang Yafeng Y Chen Yu Y Lin Jihong J Liu Chao C Kang Mingqiang M Tang Weifeng W

Oncotarget 20170904 44

The objective of this case-control study was to extensively explore the relationship of <i>Cytotoxic T-lymphocyte antigen-4</i> (CTLA-4) tagging polymorphisms with susceptibility to non-small-cell lung cancer (NSCLC). We recruited 521 sporadic NSCLC cases and 1,030 non-cancer controls. The genotypes of CTLA-4 rs16840252 C>T, rs231775 G>A, rs3087243 G>A and rs733618 T>C polymorphisms were evaluated using a custom-by-design 48-Plex SNPscan Kit. Our findings revealed there was no statistically sign ...[more]

PMID: 29100337

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Project description:Background: Immune checkpoint inhibitors (ICIs), either as monotherapy or in combination with chemotherapy, have improved the therapeutic outcome for non-small cell lung cancer (NSCLC). However, the efficacy of combination therapies, such as programmed cell death 1(PD-1)/its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, in targeting different pathways remains unclear. We performed a meta-analysis to determine whether the addition of a CTLA-4 inhibitor to PD-1/PD-L1 therapy improves the efficacy of PD-1/PD-L1 monotherapy in NSCLC. Methods: We systematically searched various electronic databases for suitable trials. Only randomized controlled trials (RCTs) comparing the clinical efficacy of PD-1/PD-L1 with and without CTLA-4 were included in the analyses. The meta-analysis software RevMan 5.3 was used for statistical analyses. Results: A total of seven RCTs were retrieved. The results suggested that the combination of CTLA-4 and PD-1/PDL-1 inhibitors did not show enhanced efficacy over PD1/PDL-1 inhibitor monotherapy as determined by overall survival (OS) (HR = 0.98, 95% CI = 0.84-1.14, p = 0.79), progression-free survival (PFS) (HR = 0.92, 95% CI = 0.81-1.06, p = 0.25), and objective response rate (ORR) (HR = 1.08, 95% CI = 0.96-1.21, p = 0.19). Furthermore, the combination immunotherapy was associated increased toxicity as evidenced by increased incidence of any type adverse events (AEs) (RR = 1.06, 95% CI = 1.00-1.13, p = 0.03), grade ≥3 immune-mediated AEs (RR = 1.58, 95% CI = 1.36-1.82, p < 0.05), and treatment discontinuation (RR = 1.83, 95% CI = 1.46-2.28, p < 0.05). Conclusion: Combining anti-CTLA-4 with anti-PD-1/PD-L1 therapy did not improve the therapeutic efficacy, and was associated with greater toxicity than anti-PD-1/PD-L1 monotherapy in patients with advanced NSCLC. Further investigation of the combination immunotherapy in specific subsets of patients is warranted to identify and define the patient-specific benefits of this combination. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023435399.

Dataset Information

Investigation of Cytotoxic T-lymphocyte antigen-4 polymorphisms in non-small cell lung cancer: a case-control study.

Publications

Investigation of <i>Cytotoxic T-lymphocyte antigen-4</i> polymorphisms in non-small cell lung cancer: a case-control study.

Similar Datasets

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