Role of enterocyte-specific gene polymorphisms in response to adjuvant treatment for stage III colorectal cancer.

Suenaga, Mitsukuni; Cao, Shu; Zhang, Wu; Matsusaka, Satoshi; Okazaki, Satoshi; Berger, Martin D.; Miyamoto, Yuji; Schirripa, Marta; Barzi, Afsaneh; Yamamoto, Noriko; Yamaguchi, Toshiharu; Lenz, Heinz-Josef (2020). Role of enterocyte-specific gene polymorphisms in response to adjuvant treatment for stage III colorectal cancer. (In Press). Pharmacogenetics and genomics Lippincott Williams & Wilkins 10.1097/FPC.0000000000000416

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OBJECTIVES

The enterocyte subtype of colorectal cancer (CRC) responds favorably to oxaliplatin-based adjuvant treatment for stage III CRC. We examined the clinical significance of single-nucleotide polymorphisms (SNPs) in enterocyte-related genes MS4A12 and CDX2 in response to adjuvant treatment for stage III CRC.

PATIENTS AND METHODS

A total of 350 patients with stage III CRC were included: 274 received adjuvant treatment with surgical resection (discovery cohort) and 76 received surgery alone (control cohort). In the discovery cohort, 68 patients received FOLFOX and 206 received oral fluoropyrimidine. SNPs were analyzed by PCR-based direct sequencing.

RESULTS

In the discovery cohort, the MS4A12 rs4939378 G/G variant was associated with lower 5-year survival than any A allele [70% vs. 90%, univariate: hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.03-5.06, P = 0.035; multivariate: HR 2.58, 95% CI 1.15-5.76, P = 0.021]. Patients with the CDX2 rs3812863 G/G variant had better overall survival than those with any A allele, although this was not significant in multivariate analysis (5 year-survival: 95% vs. 82%, univariate: HR 0.34, 95% CI 0.12-0.97, P = 0.034; multivariate: HR 0.39, 95% CI 0.13-1.11, P = 0.078). The SNPs did not show significant association with overall survival in the control cohort, and significant interaction was observed between MS4A12 genotypes and groups (P = 0.007).

CONCLUSION

Our findings suggest that MS4A12 and CDX2 gene polymorphisms may predict outcome in stage III CRC. However, the clinical significance of SNPs for response to oxaliplatin may differ by tumor stage.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1744-6872

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

26 Aug 2020 15:07

Last Modified:

26 Aug 2020 15:07

Publisher DOI:

10.1097/FPC.0000000000000416

PubMed ID:

32732498

BORIS DOI:

10.7892/boris.146079

URI:

https://boris.unibe.ch/id/eprint/146079

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