Association between methylenetetrahydrofolate reductase tagging polymorphisms and susceptibility of hepatocellular carcinoma: a case–control study

Abstract

Polymorphisms in one-carbon metabolism genes may influence the susceptibility to hepatocellular carcinoma (HCC). In the present study, we studied methylenetetrahydrofolate reductase (MTHFR) tagging polymorphisms in 584 HCC cases and 923 controls. Polymerase chain reaction was harnessed to detect MTHFR genotype. Overall, our results showed that genotype distribution of MTHFR rs4846048 and rs4845882 polymorphisms was not different between HCC patients and controls. MTHFR rs9651118 and rs1801133 loci were protective factors for HCC (rs9651118: CT vs. TT: adjusted odds ratio (OR) = 0.67, 95% confidence interval (CI): 0.49–0.90, P=0.008 and TC/CC vs. TT: adjusted OR = 0.70, 95% CI: 0.53–0.93, P=0.015; rs1801133: GA vs. GG: adjusted OR = 0.72, 95% CI: 0.54–0.97, P=0.031, AA/GA vs. GG: adjusted OR = 0.76, 95% CI: 0.57–0.99, P=0.045). However, MTHFR rs3753584 locus was a candidate for susceptibility to HCC (CT vs. TT: adjusted OR = 1.67, 95% CI: 1.20–2.32, P=0.003 and TC/CC vs. TT: adjusted OR = 1.59, 95% CI: 1.15–2.20, P=0.005). Results of haplotype analysis suggested that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Trs9651118 was associated with the risk of HCC (OR = 1.55, 95% CI: 1.16–2.07, P=0.003). The power of our study also confirmed these associations (the value of power >0.80). In summary, our findings suggested that MTHFR rs3753584, rs9651118 and rs1801133 polymorphisms may affect the risk of HCC in Chinese Han population. In future, our findings should be further validated in additional case–control studies.

Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 (MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients

“…No significant difference was noted between those who were homozygous or heterozygous. To the best of our knowledge, polymorphisms in this gene have not previously been reported to be associated with skin cancer although the CC variant has been shown to be protective against the development of breast cancer, 8 lung cancer 9 and gastro intestinal cancer 10 in certain ethnic groups.…”

Methylenetetrahydrofolate reductase C677T (Ala>Val, rs1801133 C>T) polymorphism decreases the susceptibility of hepatocellular carcinoma: a meta-analysis involving 12,628 subjects

“…In addition, Cui et al also suggested that this polymorphism could increase the risk of HCC [20]. However, some case-control studies indicated that the rs1801133 polymorphism in MTHFR gene might decrease the susceptibility of HCC [21,25]. And most studies reported that this SNP in MTHFR gene could not alter the risk of HCC.…”

“…Others pooled-analyses reported that MTHFR rs1801133 polymorphism was associated with an increased risk of HCC [45][46][47][48]. Compared with these early meta-analyses, our analysis included more large sample size studies [21,25]. It is worth mentioning that these more recent case-control studies have recruited more participants and reported that rs1801133 polymorphism was a protective factor for the development of HCC.…”

“…The publication year covered from 2004 to 2019. These investigations were performed in different populations: three were conducted in mixed populations [28,29], four were carried out in Caucasians [26,27], and twelve involved Asians [19][20][21][22][23][24][25]. The MTHFR rs1801133 genotypes are summarized in Table 2.…”

Associations of the <em>MTHFR</em> rs1801133 polymorphism with gastric cancer risk in the Chinese Han population

“…It was found that rs1801133 was associated with the risk of colorectal cancer (19,20), ovarian cancer (17), gastric cancer (21) and liver cancer (22). To further verify whether rs1801133 is associated with the risk of gastric cancer, a case-controlled study was performed using individuals recruited from Zhenjiang (Jiangsu, China).…”