Abstract:Purpose
Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between gene-nutrient interactions and the risk of non-Hodgkin lymphoma (NHL).
Methods
We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and gene-nutrient interactions in relation to NHL risk among 518 incident cases and 597 population-… Show more
“…Among all the identified single nucleotide polymorphisms (SNPs) in this gene, C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131), likely associated with reduced enzyme activity, have been widely investigated in a variety of diseases, such as psychiatric disorders11, congenital anomalies12, colorectal cancer13, and so on. Numerous studies have focused on the relationship between these two polymorphisms and NHL risk1415161718192021222324252627282930313233343536373839, but the conclusions remain controversial. The discrepancies among studies may be ascribed to the relatively small sample size in each investigation as well as ethnicity difference.…”
Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies.
“…Among all the identified single nucleotide polymorphisms (SNPs) in this gene, C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131), likely associated with reduced enzyme activity, have been widely investigated in a variety of diseases, such as psychiatric disorders11, congenital anomalies12, colorectal cancer13, and so on. Numerous studies have focused on the relationship between these two polymorphisms and NHL risk1415161718192021222324252627282930313233343536373839, but the conclusions remain controversial. The discrepancies among studies may be ascribed to the relatively small sample size in each investigation as well as ethnicity difference.…”
Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies.
“…Additionally, 6 studies were conducted in Caucasian patients; the remaining 2 studies were conducted in patients from mixed ethnic groups. All studies were population-based designed; 7 studies of genotype distribution in the controls were in line with HWE except the study conducted by Li et al [ 28 ]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…After excluding the study by Li et al [ 28 ] because the genotype frequencies in the controls deviated from HWE, we conducted further analysis and determined that the positive result was converted into a negative one. No significant association was found in the stratification analysis by tumor subtype.…”
BackgroundSerine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship.MethodsThe meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association.ResultsEight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01–1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00–1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00–1.21).ConclusionSHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.
“…Also, reasons for nonparticipation may have differed between cases and controls and self-selection of systematically different controls may have taken place, which could have led to spurious findings. Moreover, results from two large population-based case-control studies that investigated gene-nutrient interactions among determinants of one-carbon metabolism on the risk of NHL, suggested that the NHL risk associated with one-carbon metabolizing pathway genes seems to be contingent upon the dietary intakes of nutrients related to one-carbon metabolism (47,48). These intriguing new results require replication in future epidemiologic studies.…”
Background: Previous epidemiologic research suggests a protective role of one-carbon nutrients in carcinogenesis. Folate, however, may play a dual role in neoplasms development: protect early in carcinogenesis and promote carcinogenesis at a later stage. We prospectively examined associations between intake of total folate, methionine, riboflavin, vitamin B6, and risk of lymphoid and myeloid neoplasms (including subtypes) and investigated whether alcohol modified the effects of folate.Methods: The Netherlands Cohort Study consists of 120,852 individuals who completed a baseline questionnaire in 1986, including a 150-item food-frequency questionnaire. After 17.3 years of follow-up, 1,280 cases of lymphoid and 222 cases of myeloid neoplasms were available for analysis.Results: Intakes of folate, methionine, and riboflavin were not associated with lymphoid or myeloid neoplasms. For vitamin B6, a statistically significantly increased myeloid neoplasms risk was observed (highest vs. lowest quintile: HR ¼ 1.87; 95% confidence intervals, 1.08-3.25). When analyzing by lymphoid and myeloid neoplasms subtypes, no clear associations were observed for most subtypes, with just a few increased risks for some subtypes and nutrients. Some risks became nonsignificant after excluding early cases. No interaction between alcohol and folate was observed.Conclusions: We observed a few significant positive associations; however, some of these would be expected to arise due to chance alone. Furthermore, some risks became nonsignificant after excluding early cases. Therefore, we conclude that there is no association between one-carbon nutrient intake and risk of lymphoid and myeloid neoplasms.Impact: This study contributes substantially to the limited and inconclusive evidence on the association with one-carbon nutrients. Cancer Epidemiol Biomarkers Prev; 23(10); 2153-64. Ó2014 AACR.
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