Discussion The etiology of gastric cancer is multifactorial, multigenetic and multistage [24, 25]. It is known that during carcinogenesis, TGF-β can switch from a tumor suppressor to a tumor enhancer in the later stages of cancer [26]. With dual role in cancer development, there is great interest in analyzing the role of genetic variation in TGFB1 in cancer progression and patient survival. For PF-6463922 concentration example, the TGFB1 -509C>T and rs1982073 (or rs1800470) polymorphisms have

been shown to be associated with breast cancer survival in a Chinese population [27–30] and chemoradiotherapy response in 175 Finnish patients with head and neck squamous cancer[31], respectively. However, neither TGFB1 Wortmannin +869T>C nor +915G>C polymorphisms showed any association with tumor relapse and progression in bladder tumors without muscular invasive in a Spanish population [32]. While a Korean study showed that the variant T genotypes of the TGFB1 -509C>T SNP were associated with a reduced risk of lung cancer [33], a Chinese click here study of 414 patients and 414 controls [34] reported that the genotypes were not associated with an overall risk of developing gastric cancer but with a decreased risk of risk of stage I or II gastric cancer.

However, no survival analyses were presented Tyrosine-protein kinase BLK in these studies. As noted, we did not find any statistical evidence to support a significant association between TGFB1 polymorphisms and overall survival in gastric cancer. However, the significant association between TGFB1+ 915 CG/CC genotypes and 2-year survival for all gastric cancer patients suggests that this TGFB1 variant may have attenuated the role of TGF-β1 as a tumor suppressor in the earlier stage of tumor progression. It is also known that TGF-β1 can switch from a tumor

suppressor to a tumor enhancer in the late stage of cancer [26]. Once the tumors had grown bigger and become metastatic, the resultant increase in somatic mutations or gains in the copies of oncogenes may have outweighed the role of the suppressor variants in the late stages of the tumor, leading to no difference in overall survival of the patients with different genotypes of the TGFB1+ 915 G>C SNP. However, this speculation needs to be validated in more rigorously designed studies with a much larger sample size and more information on the mutation spectrum in the tumors. VEGF, as a key mediator of angiogenesis, also plays an important role in the development of cancers. VEGF polymorphisms have also been shown to be associated with survival in both gastric cancer and colorectal cancer [35, 36]. However, the results from published studies remain inconsistent rather than conclusive.