MTHFR enzyme plays a pivotal role in intracellular folate and homocysteine metabolism, which are fundamental for DNA methylation, synthesis, and genomic integrity [13]. Imbalance in the circulating concentrations of folate,homocysteine and vitamin B12 may cause DNA damage leading to genetic instability which is related to the occurrence of several cancers including prostate cancer [14–16]. In fact, it was reported that folate deficiencywill induce in CpG island hypermethylation and uracil misincorporation into DNA strands, resulting in genetic and epigenetic instability observed in murine PCa models.However, a high level of serum folate andhomocysteine increases prostate cancer progression. This conflicting results may reflect the potential dualistic role of folate in prostate carcinogenesis [15]. Moreover, high serum level of vitamin B12 and homocysteinehas been associatedwithprostate cancer risk [15, 17]. Unlike previous findings, in our study, we found no relationship between these vitamins, homocysteineand the risk of prostate cancer development. Our results were consistent with the findings of Weinstein et al [18] andBeilby et a [19].
As for the relationship between MTHFR polymorphisms and prostate cancer, the results showed no significant differences in our population. The results were consistent with several meta-analyses which have reported that C677T and A1298C polymorphisms were not associated with prostate cancer in Caucasian, mixed, and Asian populations [11, 20–22]. However, some published data showed a positive association between the MTHFR C667T polymorphism and PCa development [10, 23]. Moreover, it was reported that the genotype 677 TT exerts a protective effect on prostate cancer risk in the Spanish and Asian populations [24, 25]. As well as, Cicek et al.[26] suggested that 677T and 1298A may be associated with the reduction of prostate cancer progression. These conflicting results may be due to the methods of control selection, their dietary differences, geographical regions, ethnic origins, as well as their exposure to diverse environmental risk factors.
Tobacco isidentifiedas an environmental risk factor for cancercausing30% of all human cancers including PCa [27] .Two several biologicalmechanisms were proposed to promote carcinogenesis in the prostate: First of all, tobacco contains a multiple carcinogenic compounds, which can indirectly induce PCa through their interaction with androgen receptors [28]. Secondly, it was reported that men smokers have elevated levels of circulating testosterone, androstenedione, and DHT [29]. Nevertheless; other studies have not supported the link between tobacco smoking and prostate cance [30]. Similarly, our results showed that tobacco consumption was not associated with prostate cancer (OR = 1.001, P = 0.996). The same results have been found in the Western and Eastern populations of Algeria [31–32].
However, age is among the strongest prostate cancer risk factors, more than 80% of prostate cancer is detected in men who are 65 years or older [2]. Actually, it was shown that 42% of 50 years old men have already developed microscopic evidence of this disease [33]. Our results reveal that age hasinfluence on the development ofprostate cancer(OR = 1.178, P = 0.00).
Furthermore, in our study, the family history is an independent risk factor ofPCa (OR = 2.53, P = 0.009). Several studies reported an increased PCa risk with a positive family history in different populations [34, 35]. Diverse meta-analyses have found that there was a 2-3-fold increased risk of prostate cancer in men who have first-degree family members affected and the risk was slightly lower among those with a second-degree family member.In addition, men can be vulnerable to prostate cancer at an early age in case of having many family members affected [36, 37]. Moreover, our results are similar to those of Western and Eastern populations of Algeria [31, 38]. Due to the significance of these findings, it goes without saying that an earlier diagnosis is essential, especially for men with a higher degree of prostate cancer risk.