Case Control Study
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World J Gastroenterol. Sep 14, 2014; 20(34): 12212-12216
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12212
Polymorphisms of MTHFR and susceptibility to oesophageal adenocarcinoma in a Caucasian United Kingdom population
Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang
Richard Keld, Manyi Thian, Chia Hau, Jamil Sajid, Narveen Kumar, Yeng Ang, Department of Gastroenterology, Royal Albert Edward Infirmary, Wigan, Lancashire WN1 2NN, United Kingdom
Yeng Ang, Faculty of Human and Medical Sciences, University of Manchester, Manchester, Salford M6 8HD, United Kingdom
Author contributions: Keld R and Ang Y contributed to the ideas; Keld R, Thian M, Hau C, Sajid J, Kumar N and Ang Y performed the research; Keld R, Thian M and Ang Y wrote the paper.
Supported by Endowment funds of the Wrightington, Wigan and Leigh NHS Foundation Trust; Ang Y received support from Comprehensive Local Research Network of Greater Manchester and Cheshire, United Kingdom (flexibility and sustainability grant)
Correspondence to: Yeng Ang, Consultant Gastroenterologist and Honorary Senior Lecturer, Faculty of Human and Medical Sciences, University of Manchester, Manchester, Stott Lane, Salford M6 8HD, United Kingdom. yeng.ang@srft.nhs.uk
Telephone: +44-161-2065798 Fax: +44-161-2065798
Received: January 10, 2014
Revised: March 20, 2014
Accepted: May 12, 2014
Published online: September 14, 2014
Processing time: 251 Days and 14.3 Hours
Abstract

AIM: To identify if methylene tetra-hydrofolatereductase (MTHFR) C677T polymorphisms are associated with oesophageal adenocarcnomas in a Caucasian population and to test whether folic acid and homocysteine levels are linked with cancer risk.

METHODS: A case control study comprising of 58 non cancer and 48 cancer patients, MTHFR C667T genotyping was made and serum folate, homocysteine and vitamin B12 levels were made. Tumour stage, differentiation and survival was recorded. A P value of less than 0.05 was taken to be significant. The χ2 used to compare discrete variables and the Mantel-Cox was used to compare survival. A P value less than 0.05 was deemed to be significant.

RESULTS: MTHFR polymorphisms is associated with an increased risk of several cancers. A link between MTHFR C677T polymorphisms and oesophageal squamous cell carcinoma and gastric cardia adenocarcinoma has been demonstrated in at risk Chinese populations. In a Western European population the role of the MTHFR gene has not previously been investigated in the setting of oesophageal adenocarcinoma. No association between folic acid levels and cancer patients was found. The unstable MTHFR 667 TT genotype occurred in 11% cancers and 7% controls, but statistical significance was not reached, homocysteine levels and folic acid levels were not affected, cancer patients with TT genotype displayed a trend for a shorter survival 7 mo vs 20 mo. Serum vitamin B12 levels were higher in the cancer group. The MTHFR 667 TT genotype is much lower than previous population studies.

CONCLUSION: We conclude that serum folic acid and MTHFR polymorphisms are not associated with an increased risk of oesophageal adenocarcinoma, although cancers with unstable TT genotype may indicate a more aggressive disease course.

Keywords: Polymorphisms of 5,10-methylenetetrahydrofolate reductase; Oesophageal adenocarcinoma; Caucasian population; Helicobacter pylori; Polymorphism

Core tip: Our paper is the first Western population study and shows that methylene tetra-hydrofolatereductase (MTHFR) C677T polymorphisms is not associated with risk of oesophageal adenocarcinoma in contrast to Chinese and perhaps Far East populations. This highlights the difference in terms of the biology, genetics and epigenetics between Western and Eastern cancer populations and adds to our understanding of the etiology of oesophagogastric cancers.