Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis

Abstract

Folate-pathway gene polymorphisms have been implicated in several cancers and investigated inconclusively in relation to prostate cancer. We conducted a systematic review, which identified nine case-control studies (eight included, one excluded). We also included data from four genome-wide association studies and from a casecontrol study nested within the UK population-based Prostate Testing for Cancer and Treatment study. We investigated by meta-analysis the effects of eight poly-

The MTHFR C677T Polymorphism and Prostate Cancer Risk: New Findings from a Meta-analysis of 7306 Cases and 8062 Controls

“…The relatively low incident rate of prostate cancer in Asian population (American Cancer Society, 2011) and small sample sizes in the recent Asian studies could be the very reason why the protective effect of the polymorphism was diluted in overall studies; it is supported by the sensitivity tests which removed three European studies (Kimura et al, 2000;Heijmans et al, 2003;Collin et al, 2009) respectively from overall studies and detected such protective effect again. However, we still doubt whether it is proper to pool all studies together here to evaluate the association between a polymorphism and prostate cancer risk without the consideration of gene background, living habits and baseline metabolism profile of population in studies.…”

“…We identified two meta-analysis (Bai et al, 2009;Collin et al, 2009) published in 2009 concerning similar topic as we did during the literature search; both of them examined the effect of MTHFR SNP C677T on prostate cancer risk, but no consistent conclusion was achieved. Collin found no effect of MTHFR C677T or any of the other alleles under all models while Bai stated that "the 677T allele was more likely to exert a protective effect on prostate cancer risk (OR = 0.81, 95% CI: 0.68-0.98) with a recessive genetic model".…”

“…We included 15 independent studies (Kimura et al, Heijmans et al, 2003;Cicek et al, 2004;Singal et al, 2004;Van et al, 2006;Johansson et al, 2007;Reljic et al, 2007;Marchal et al, 2008;Stevens et al, 2008;Collin et al, 2009;Muslumanoglu et al, 2009;Cai et al, 2010;Safarinejad et al, 2010;Wu et al, 2010;Kucukhuseyin et al, 2011) published during 2000 to 2011 with a total of 7306 cases and 8062 controls in our meta-analysis. According to the background of control population, 6 were hospital-based case-control studies (Kimura et al, 2000;Singal et al, 2004;Marchal et al, 2008;Muslumanoglu et al, 2009;Cai et al, 2010;Wu et al, 2010), 5 were population-based studies (Cicek et al, 2004;Johansson et al, 2007;Reljic et al, 2007;Safarinejad et al, 2010;Kucukhuseyin et al, 2011) and the rest 4 were populationbased studies nested in cohort (Heijmans et al, 2003;Van et al, 2006;Stevens et al, 2008;Collin et al, 2009).…”

“…According to the background of control population, 6 were hospital-based case-control studies (Kimura et al, 2000;Singal et al, 2004;Marchal et al, 2008;Muslumanoglu et al, 2009;Cai et al, 2010;Wu et al, 2010), 5 were population-based studies (Cicek et al, 2004;Johansson et al, 2007;Reljic et al, 2007;Safarinejad et al, 2010;Kucukhuseyin et al, 2011) and the rest 4 were populationbased studies nested in cohort (Heijmans et al, 2003;Van et al, 2006;Stevens et al, 2008;Collin et al, 2009). One study (Cicek et al, 2004) used sibling as control population.…”

“…Two of the 15 studies were conducted in mixed ethnicities (Cicek et al, 2004;Singal et al, 2004) (Cicek: Caucasian/African-American/Latino; Singal: Caucasian/ African-American), two in yellow Asian (Cai et al, 2010;Wu et al, 2010) and the rests in Caucasian (Kimura et al, 2000;Heijmans et al, 2003;Van et al, 2006;Johansson et al, 2007;Reljic et al, 2007;Marchal et al, 2008;Stevens et al, 2008;Collin et al, 2009;Muslumanoglu et al, 2009;Safarinejad et al, 2010;Kucukhuseyin et al, 2011). In terms of the residential region of the participants, the most recent 5 studies were all conducted in Asia (Muslumanoglu et al, 2009;Cai et al, 2010;Safarinejad et al, 2010;Wu et al, 2010;Kucukhuseyin et al, 2011), 3 of the rest 10 were in the USA (Cicek et al, 2004;Singal et al, 2004;Stevens et al, 2008) and 7 in Europe (Kimura et al, 2000;Heijmans et al, 2003;Van et al, 2006;Johansson et al, 2007;Reljic et al, 2007;Marchal et al, 2008;Collin et al, 2009). All studies extracted DNA from blood/serum samples for further test except one (Singal et al, 2004), in which DNA was isolated from the archived paraffin blocks.…”