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Germ line polymorphisms as predictive markers for pre-surgical radiochemotherapy in locally advanced rectal cancer: a 5-year literature update and critical review

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Abstract

Purpose

Locally advanced rectal cancer is currently treated with pre-surgical radiotherapy and chemotherapy. Approximately one-half of patients obtain a relevant shrinkage/disappearance of tumour, with major clinical advantages. The remaining patients, in contrast, show no benefit and possibly need alternative treatment. To provide the best therapeutic option for each individual patient, predictive markers have been widely researched. This review was undertaken to evaluate recent progress made in this field.

Methods

A systematic literature search was performed using PubMed and Scopus database, focused on germ line gene polymorphisms as biomarkers and response and toxicity as outcomes. Because an exhaustive previous review was available describing findings up to 2008, we restricted our analysis to the last 5 years.

Results

Ten original research articles were found, reporting promising results for some candidate genes in drug metabolism (TYMS, MTHFR), DNA repair (XRCC1, OGG1, CCND1) and inflammation (SOD2, TGFB1)/immunity (IL13) pathways, but with no firm conclusion. All the studies had small sample size and were defined as exploratory. This review highlights pivotal molecular, clinical, genetic and statistical issues in the investigation of genetic polymorphisms as outcome predictors for rectal cancer and offers suggestions for future development.

Conclusions

What emerges is a clear need for new proposals, especially in view of the increasing evidence for tumour-host and gene-gene interactions during anticancer treatment, together with stronger adherence to proper methodological requirements.

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Abbreviations

5-FU:

5-Fluorouracil

5-MTHF:

5-Methyl-tetrahydrofolate

5,10-MTHF:

5,10-Methylenetetrahydrofolate

CART:

Classification and regression tree

CT:

Chemotherapy

DFS:

Disease-free survival

GWAS:

Genome-wide association studies

MAF:

Minor allele frequency

MTHFR:

Methylenetetrahydrofolate reductase

OGG1:

Oxoguanine DNA glycosylase

OS:

Overall survival

q-RT-PCR:

Quantitative, retro-transcription polymerase chain reaction

RC:

Rectal cancer

RCT:

Radiochemotherapy

RR:

Response rate

RT:

Radiotherapy

SNP:

Single nucleotide polymorphism

SOD:

Superoxide dismutase

TGF:

Transforming growth factor

TNF-α:

Tumour necrosis factor alpha

TYMS/TS:

Thymidylate synthase gene/protein

UTR:

Untranslated region

XRCC1:

X-ray cross-complementing group 1

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Further reading

  1. PubMed, U.S. National Institute of Health, National Library of Medicine. http://www.ncbi.nlm.nih.gov/pubmed. Accessed 10 July 2014

  2. Scopus, Elsevier. http://www.scopus.com. Accessed 27 Sep 2014

  3. Vanderbilt University, Department of Biostatistic. Power and sample size calculation. http://biostat.mc.vanderbilt.edu/wiki/Main/PowerSampleSize. Accessed 15 Aug 2014

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Acknowledgments

We thank Dr. Eros Ferrazzi for the critical analysis, Dr. Felice Pasini for support to this paper, Dr. Stephen D. Skaper for linguistic input and Roberta Sato for search on web database. This work was supported in part by 5x1000 funds from Lega Italiana per la Lotta contro i Tumori.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Largo Meneghetti, 2, 35131, Padua, Italy

    Elisa Pezzolo & Pietro Giusti

  2. Department of Oncology, Azienda ULSS 18-Rovigo, S. Maria della Misericordia Hospital, Viale Tre Martiri, 140, 45100, Rovigo, Italy

    Elisa Pezzolo, Yasmina Modena & Milena Gusella

  3. Neuroscience Institute, National Research Council, Via Giustiniani 2, 35128, Padua, Italy

    Barbara Corso

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  1. Elisa Pezzolo
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  2. Yasmina Modena
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Correspondence to Milena Gusella.

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Pezzolo, E., Modena, Y., Corso, B. et al. Germ line polymorphisms as predictive markers for pre-surgical radiochemotherapy in locally advanced rectal cancer: a 5-year literature update and critical review. Eur J Clin Pharmacol 71, 529–539 (2015). https://doi.org/10.1007/s00228-015-1824-0

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