Plasma homocysteine levels and genetic polymorphisms in folate metablism are associated with breast cancer risk in chinese women

Abstract

BackgroundFolate plays a pivotal role in DNA synthesis, repair, methylation and homocysteine (Hcy) metabolism. Therefore, alterations in the folate-mediated one-carbon metabolism may lead to abnormal methylation proliferation, increases of tumor/neoplasia and vein thrombosis/cardiovascular risk. The serine hydroxymethyhransferase (SHMT), methionine synthase (MS), methionine synthase reductase (MTRR) and cystathionine beta synthase (CBS) regulate key reactions in the folate and Hcy metabolism. Therefore, we investigated whether the genetic variants of the SHMT, MS, MTRR and CBS gene can affect plasma Hcy levels and are associated with breast cancer risk.MethodsGenotyping was performed by PCR-RFLP method. Plasma Hcy levels were measured by the fluorescence polarization immunoassay on samples of 96 cases and 85 controls.Results(a) The SHMT 1420 T, MS 2756G, MTRR 66G allele frequency distribution showed significant difference between case and controls (p < 0.01 ~ 0.05). (b) The concentration of plasma Hcy levels of SHMT 1420TT was significantly lower than that of the wild type, while the plasma Hcy levels of MS 2756GG, CBS 699TT/1080TT significantly higher than that of the wild type both in case and controls. The plasma Hcy levels of MTRR 66GG was significantly higher than that of wild type in cases. The plasma Hcy levels of the same genotype in cases were significantly higher than those of controls except SHMT 1420CC, MS 2756AA, MTRR 66GG; (c) Multivariate Logistic regression analysis showed that SHMT C1420T (OR = 0.527, 95% CI = 0.55 ~ 1.24), MS A2756G (OR = 2.32, 95% CI = 0.29 ~ 0.82), MTRR A66G (OR = 1.84, 95% CI = 0.25 ~ 1.66) polymorphism is significantly associated with breast cancer risk. And elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR = 4.45, 95% CI = 1.89-6.24 for the highest tertile as compared with the lowest tertile).ConclusionsThe current study results seem to suggest a possibility that SHMT C1420T mutation may be negatively correlated with breast cancer susceptibility; while MS A2756G and MTRR A66G mutation may be positively associated with breast cancer risk. SHMT C1420T, MS A2756G, MTRR A66G, CBS C1080T, CBS C699T locus mutation may be factors affecting plasma levels of Hcy. The plasma Hcy levels could be metabolic risk factor for breast cancer risk to a certain extent.

Clinical significance of SHMT1 rs1979277 polymorphism in Asian solid tumors: evidence from a meta-analysis

“…Several studies indicated that there was no association between the SHMT1 C1420T polymorphism and breast cancer risk (Lissowska et al, 2007;Xu et al, 2007;Yu et al, 2007;Bentley et al, 2010;Vainer et al, 2010;Naushad et al, 2012;Wu et al, 2014). However, Naushad et al (2011) and Mohammad et al (2011) proved that rs1979277 polymorphism reduces the risk of breast cancer, which were similar with our result.…”

“…Three articles were excluded because of a lack of usable data. Eventually, a total of 23 eligible studies involving 14,409 cases and 16,996 controls were included in the pooled analyses (Chen et al, 2004;Zhang et al, 2005;Koushik et al, 2006;Hazra et al, 2007;Lissowska et al, 2007;Moore et al, 2007;van den Donk et al, 2007;Wang et al, 2007;Xu et al, 2007;Yu et al, 2007;Guerreiro et al, 2008;Steck et al, 2008;Stevens et al, 2008;Bentley et al, 2010;Komlosi et al, 2010;Vainer et al, 2010;Curtin et al, 2011;Mohammad et al, 2011;Naushad et al, 2011Naushad et al, , 2012Weiner et al, 2012;Succi et al, 2014;Wu et al, 2014). The characteristics of the studies selected are summarized in Table 1.…”

Haplotypes of the MTHFR gene are associated with an increased risk of breast cancer in a Han Chinese population in Gansu province

“…Breast cancer is the major cause of cancer‐related deaths in women worldwide and is, by far, the second leading cause of death in Chinese women . Over the past few decades, a series of clinical studies showed that homocysteine is an independent risk factor for breast cancer, as well as other types of cancers, cardiovascular disease, and birth defects . Homocysteine is produced during one‐carbon metabolism, and its concentration in tissue is maintained at low levels via tight regulation .…”

“…Breast cancer is the major cause of cancer-related deaths in women worldwide (1) and is, by far, the second leading cause of death in Chinese women (2). Over the past few decades, a series of clinical studies showed that homocysteine is an independent risk factor for breast cancer, as well as other types of cancers, cardiovascular disease, and birth defects (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

Use of folic acid during pregravid preparation and pregnancy

“…Но сочетанное действие генетических и средовых факторов может иметь неблагоприятные последствия, условно объединяемые в три группы: онкологический риск, обусловленный недо-статочностью ДГФР и других энзимов фолатного цикла [13], гипергомоцистеинемия, связанная с недостаточно-стью МТГФР [14], и нарушения клеточного развития, об-условленные недостатком фолатов.…”