Genetic polymorphisms in themethylenetetrahydrofolate reductase andthymidylate synthase genes and risk of hepatocellular carcinoma

Abstract

H epatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer deaths. 1 The overall 5-year survival for patients with HCC is less than 10%.Only 30% of patients with HCC are considered candidates for surgical resection; however, the recurrence rate after surgery is approximately 40% to 50%. 2 The major risk factors for HCC vary somewhat with its geographical distribution. Chronic infection with hepatitis B virus (HBV) is by far the most important risk factor for HCC in humans and is the primary cause of this cancer in highrisk areas, including China and Africa. 3,4 Chronic infection with hepatitis C virus (HCV) is another risk factor for HCC and has an increasingly prominent role in the development of HCC in countries such as the United States where rates of infection with HBV are relatively low. 5 Other environmental risk factors for HCC include dietary aflatoxin, which plays a prominent role in highrisk areas such as China and Africa; excessive alcohol intake; cigarette smoking; diabetes; and obesity. [6][7][8] Given that only a minority of people exposed to these risk factors eventually develop HCC, other cofactors (environmental and/or genetic) are likely to be involved in the development of HCC in humans.Experimental studies have shown that diets deficient in methyl groups (folate, methionine, and choline) can induce HCC in rodents 9,10 along with an increased level of uracil in DNA and accumulated DNA strand breaks in the P53 gene of the hepatocytes. [11][12][13] Thymidylate is a

Polymorphisms of Thymidylate Synthase in the 5′- and 3′-Untranslated Regions and Gastric Cancer

“…A study conducted by Kuramochi et al suggested that the status of the TS 5 0 -UTR polymorphism was an independent predictive marker for survival benefit from 5-FU-based therapy in esophageal adenocarcinoma patients [31]. A case-control study conducted by Yuan et al showed that individuals with TS 3 0 UTR ins6/del6 or del6/del6 allele had a statistically significant 50% reduction in risk of hepatocellular carcinoma [32]. A case-control study conducted by Wang et al showed that individuals with TS 5 0 UTR 3Rc/3Rc genotype had a statistically significant increased risk of pancreatic cancer [33].…”

Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review

“…For decades of years, there were a lot of studies explored the relationship of polymorphisms of candidate gene and HCC (Yuan et al 2007;Tanabe et al 2008;Akkiz et al 2009;Imaizumi et al 2009;Ognjanovic et al 2009). Because liver is the largest metabolic organ in human body, the candidate SNPs studied mainly related to the genes encoding carcinogen-metabolising enzymes, such as cytochrome P450 superfamily (CYPs) (Rossi et al 2003;Silvestri et al 2003;Yuan et al 2008), UDP-glucuronosyltransferases (UGTs) (Vogel et al 2001;Wang et al 2004), and hemochromatosis (HFE) (Shi et al 2005;Ropero et al 2007;Ezzikouri et al 2008a, b).…”

Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA

“…The design of the Los Angeles HCC Study has been described previously (12,21). Briefly, cases were newly diagnosed HCC patients of black, Hispanic or non-Hispanic white Americans residing in Los Angeles County who were between 18 and 74 years of age at diagnosis from January 1984 through December 2001.…”