Smoking, Green Tea Consumption, Ugt1a1 Polymorphism Associated With Lung Cancer Risk

Experimental studies have shown that tea preparations and tea polyphenols may inhibit the induction of a variety of cancers, including lung cancer. However, epidemiologic studies on tea consumption and cancer are limited and the results are inconclusive. Tea catechins could be rapidly glucuronidation by human uridine diphosphate glucuronosyltransferases (UGTs). The human UGT1A1 gene is located in chromosome 2q37. A polymorphism (TA)6 to (TA)7 change in the TATA-box of the promoter region of the UGT1A1 gene, and the position 211 of exon 1 of the UGT1A1 gene contains a G to A transition (G71R) have been reported. These structural variations are believed to result in about 30-80 percent reduction in enzymatic activity. Therefore, smokers who drank less green tea might have an elevated risk of lung cancer. Individuals who experienced non-susceptible UGT1A1 genotype and drank greater green tea might have a decreased risk of lung cancer. We designed a hospital-based case-control study to evaluate the effects of smoking, green tea intake, and genetic polymorphism of UGT1A1 on the risk of lung cancer. A total of 136 primary lung cancer patients and 272 individual-matched controls were included. Interviews were administered using the structured questionnaire that covered demographic characteristics and life styles, including smoking habits, green tea consumption, dietary intake of fruits and vegetables, cooking practices and family history of lung cancer. The genotypes for UGT1A1 G71R (Gly71Arg) and TATA box [(TA)6 to (TA)7] were identified by polymerase chain reaction and restriction fragment length polymorphism and short tandem repeat polymorphism. Our result showed that smoking, green tea consumption less than one cup per day, exposure to the fume of cooking and family history of lung cancer were associated with elevated lung cancer risk. After adjusting the effects of the fume of cooking and family history of lung cancer, the relative risks was significantly higher in heavy smokers without green tea drinking, as compared to non-smokers who drank green tea more than one cups per day (odds ratio [OR] = 26.6; 95% C.I. = 6.6-107.1), and in comparison to non-smokers who drank green tea more than ten years (OR = 42.0, 95% C.I.= 7.7-228.3), respectively. Among green tea drinkers, those who carrying the low activity of UGT1A1 G71R R allele were associated with a significantly reduced risk of lung cancer compared with those who carrying the high activity of G71R G allele. Similar result in the lung cancer risk and genotype of UGT1A1 TATA box was observed, although it did not reach a significance. In conclusion, green tea drinkers who carrying low activity of UGT1A1 genotype might metabolize tea polyphenols slowly; and thus experienced a reduced risk of lung cancer caused by smoking. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3931.