title: MTHFR 677C>T polymorphism and the risk of breast cancer: evidence from an original study and pooled data for 28031 cases and 31880 controls.
abstract: BACKGROUND
  Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent.
  
  
  RESULTS
  We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067).
  
  
  CONCLUSIONS
  677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer.
authors: Division of Endocrinology, Central Drug Research Institute, Lucknow, India; Department of Pathology, King George's Medical University, Lucknow, India.
authors: Singh
authors: S
authors: Pooja
authors: Centre for Genetics and Inherited Diseases (CGID), Taibah University, Al- Madinah, Kingdom of Saudi Arabia; Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
authors: Justin
authors: J
authors: Carlus
authors: Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
authors: Deepa
authors: D
authors: Sekhar
authors: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
authors: Amirtharaj
authors: A
authors: Francis
authors: Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
authors: Nishi
authors: N
authors: Gupta
authors: Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
authors: Rituraj
authors: R
authors: Konwar
authors: All India Institute of Medical Sciences, Bhopal, India.
authors: Sandeep
authors: S
authors: Kumar
authors: Department of Surgery, King George's Medical University, Lucknow, India.
authors: Surender
authors: S
authors: Kumar
authors: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
authors: Kumarasamy
authors: K
authors: Thangaraj
authors: Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
authors: Singh
authors: S
authors: Rajender
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D055815:Young Adult
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)