[Interactions between lifestyle, methylanetetrahydrofolate reductase gene and polymorphisms in thymidylate synthase gene with risk of stomach cancer].
OBJECTIVE
To evaluate interactions between lifestyle, methylanetetrahydrofolate reductase gene (MTHFR) and polymorphisms in the 3'-untranslated region (3'-UTR) of the thymidylate synthase gene (TS) with reference to development of stomach cancer (SC).


METHODS
We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. TS genotypes were identified by polymerase chain reaction.


RESULTS
(1) The frequencies of TS genotypes (+6 bp/+6 bp, +6 bp/-6 bp and -6 bp/-6 bp) among the cases were 5.6%, 47.7% and 46.7% and among the controls were 9.0%, 54.0% and 37.0%, respectively. Individuals identified as -6 bp/-6 bp genotype had a slightly higher risk for SC than those individuals with +6 bp alleles (the crude OR = 1.49, 95% CI: 0.90 - 2.47; adjusted OR = 1.36, 95% CI: 1.00 - 1.78, P = 0.047). (2) Individuals having TS -6 bp/-6 bp genotype and having smoking habit were at a significantly higher risk of developing SC (adjusted OR = 2.79, 95% CI: 1.51 - 5.18) compared with those who had +6 bp alleles with no smoking habit. Individuals having TS -6 bp/-6 bp genotype and habit of frequent alcohol drinking were at an increased risk of developing SC (adjusted OR = 1.76, 95% CI: 1.07 - 2.90) compared with those with +6 bp alleles and low consumption of alcohol. As compared with individuals with +6 bp alleles and who had habit of tea drinking, individuals who had TS -6 bp/-6 bp genotype and but without habit of tea drinking had an increased risk of developing SC (adjusted OR = 2.34, 95% CI: 1.43 - 3.82). (3) Individuals with TS -6 bp/-6 bp genotype and with MTHFR T alleles had an increased risk of developing SC (adjusted OR = 2.67, 95% CI: 1.07 - 6.70) compared with those with +6 bp alleles and with MTHRF C/C genotype.


CONCLUSIONS
Results in the present study suggested that there was a combined effect between lifestyle, MTHFR C/T or T/T genotype and TS -6 bp/-6 bp genotype in the development of SC.
Gao
Chang-ming
CM
Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing 210009, China.
Wu
Jian-zhong
JZ
Liu
Yan-ting
YT
Ding
Jian-hua
JH
Li
Su-ping
SP
Su
Ping
P
Hu
Xu
X
Kai
Hai-tao
HT
Toshiro
Takezaki
T
Kazuo
Tajima
T
D000428:Alcohol Drinking / Q000009:adverse effects; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics; D013662:Tea / Q000737:chemistry; D013940:Thymidylate Synthase / Q000235:genetics*
D013662:Tea; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase