Abstract:
:The transforming growth factor-β (TGFβ) pathway plays an important role in various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate the associations between these polymorphisms and gastric cancer susceptibility, clinicopathological parameters and survival. A case-control study was conducted in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87; p=0.001) and certain subtypes of gastric cancer including intestinal type (OR, 0.70; 95% CI, 0.57-0.87; p=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54-0.85; p=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; p=0.008). Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a significantly decreased gastric cancer risk (OR, 0.58; 95% CI, 0.62-0.91; P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI, 0.32-0.57, p<0.001). No significant correlation was observed between polymorphisms and survival of gastric cancer patients. Our results suggest that both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of gastric cancer according to clinicopathological parameters. A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric cancer risk. These findings provide clues to the biological mechanisms that underline tumor heterogeneity.
journal_name
Oncol Lettjournal_title
Oncology lettersauthors
Xu L,Zeng Z,Chen B,Wu X,Yu J,Xue L,Tian L,Wang Y,Chen M,Sung JJ,Hu Pdoi
10.3892/ol.2011.249subject
Has Abstractpub_date
2011-03-01 00:00:00pages
371-377issue
2eissn
1792-1074issn
1792-1082pii
ol-02-02-0371journal_volume
2pub_type
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