An intervention study of smoking cessation with feedback on genetic cancer susceptibility in Japan.

BACKGROUND: To evaluate whether feedback of genetic information regarding an L-myc polymorphism, identified as impacting on tobacco-related cancer risk, has an influence on smoking cessation, an intervention study was conducted. METHODS: We recruited smokers from first-visit outpatients at Aichi Cancer Center Hospital. Six hundred and seventeen participated and were allocated into two groups: the biomarker feedback group (BF) and the follow-up smoking status group (FS). The subjects were asked for their smoking status at enrolment and at 3- and 9-month follow-ups. BF subjects were notified about their L-myc genotype. RESULTS: The smoking cessation rate at 9-month follow-up was essentially the same for both BF and FS cases, at 18.8% and 17.0%, respectively (P = 0.798). However, a difference in the rate was evident with non-cancer subjects (12.7% and 8.4%, respectively, P = 0.237), especially in females (15.0% and 4.2%, respectively, P = 0.024). The non-cancer subjects informed of their genotype were more likely to quit smoking than the FS patients; particularly in those having a risky genotype, this was significant (odds ratio: 2.87, P = 0.003). Again it was most prominent in females. CONCLUSION: Feedback regarding an L-myc polymorphism did not impact on smoking cessation overall but appeared to benefit smokers without cancer. In addition, gender could affect the response to the feedback.

Significant association of interleukin 8 -251T/A polymorphism with smoking behavior in a Japanese population.

Accumulating evidence indicates that the genotype may impact on smoking behavior and a deeper understanding of the molecular basis could lead to more effective strategies for preventing initiation of the habit and to help smokers to quit. Since individual variation in airway responsiveness to cigarette smoke might have an important influence, we have focused on associations between smoking behavior and polymorphisms affecting the inflammatory cytokine, IL-8. In the present study, 453 Japanese non-cancer outpatients (191 males and 262 females) who visited Aichi Cancer Center Hospital were genotyped for the IL8 -251T/A polymorphism, and age- and sex-adjusted odds ratios (aORs) for smoking were estimated using a logistic regression model. The aORs for IL8 251-TA and AA combined, genotypes associated with high production of IL-8, were 0.52 (95% CI 0.33-0.82, P=0.004) for ever having smoked and 0.55 (0.33-0.92, P=0.023) for being a current smoker. Our results suggest that the inflammatory-prone genotype of IL8 may act to deter initiation or characteristics of the smoking habit.

Monoamine oxidase polymorphisms and smoking behaviour in Japanese.

Although nicotine dependence is one of the primary reasons why smokers cannot quit smoking, nicotine cannot explain all of the psychopharmacological effects of tobacco smoke. Accumulating evidence points to potent inhibition of monoamine oxidase (MAO) which metabolizes neurotransmitters relating to additive behaviour. We have therefore investigated the association between smoking behaviour and MAO ( variable number of tandem repeat in the promoter region and A644G) polymorphisms. The genotypes were examined in 504 Japanese outpatients (217 men and 287 women) who visited Aichi Cancer Centre Hospital. The age-adjusted odds ratios (aORs) were estimated by a logistic model. Among males, we did not find a significant association of the smoking habit with either of the polymorphisms. The median Fargastrom test for nicotine dependence (FTND) score among male current smokers was significantly higher with than without the 4-repeat allele (5.8 and 4.7, respectively). The aOR of FTND 6 versus FTND 6 was 2.72 (95% confidence interval 1.13-6.50) for males with the 4-repeat allele. Among females, the aOR of being current smokers compared to never smokers was 0.49 (0.26-0.93) for individuals with the 4-repeat allele. Our results indicate that the polymorphisms of influence the smoking habit for female, as well as the nicotine dependence and smoking initiation for male smokers. These findings among male smokers support the view that MAO affects a smokers' requirement for nicotine and may explain why some people are predisposed to tobacco addiction and why some individuals find it difficult to stop smoking.

Significant reduction in breast cancer risk for Japanese women with interleukin 1B -31 CT/TT relative to CC genotype.

OBJECTIVE: The present case-control study aimed to examine the associations between breast cancer risk and three functional polymorphisms (Interleukin (IL) -1A C-889T, IL-1B C-31T and IL-1RN 86-bp variable number tandem repeat) related to expression of IL-1beta, which combines estrogen receptor. METHODS: Cases were 231 patients with breast cancer who had been diagnosed 1 month to 6 years before their enrollment in 1999-2000 at Aichi Cancer Center Hospital. Controls were 186 non-cancer outpatients recruited during the same period at the digestive tract, breast surgery and gynecology clinics. RESULTS: There were no differences in the genotype distributions of the IL-1A and IL-1RN polymorphisms, but individuals harboring a IL-1B C-31T T allele (high expression allele) were less frequent among cases (74.3%) than among controls (84.9%). The age-adjusted odds ratio (OR) relative to CC genotype was 0.52 (95% confidence interval, 0.30-0.88) for CT genotype, 0.58 (0.32-1.02) for TT genotype and 0.54 (0.33-0.90) for CT/TT genotype. Subgroup analysis showed that the preventive effect was significantly stronger for postmenopausal women than for premenopausal women (interaction 0.30, 0.11-0.84). CONCLUSIONS: Although this is the first report on the association between breast cancer risk and IL-1B C-31T, the observed association seems plausible in a biological sense.

Genotype frequencies of 50 polymorphisms for 241 Japanese non-cancer patients.

This paper lists the genotype frequencies of 50 polymorphisms of 37 genes (ALDH2, ADRB2, ADRB3, COMT, CD36, CXCR2, CCND1, COX2, CYP2A6, CYP17, CYP19, IGF1, IL-1A, IL-1B, IL-1RN, IL-1R1, IL-6, IL-8, IL-10, LEP, Le, L-myc, MPO, MTR, MTHFR, MAO-A, NQO1, OGG1, p53, p73, Se, SRD5A2, TGF-B, TNF-A, TNF-B, XPD, and XRCC1) and 6 sets of combined genotype frequencies for 241 non-cancer Japanese outpatients. Though the genotype frequencies of 25 polymorphisms have already been reported in our previous papers, 15 polymorphisms (CD36 A52C, CXCR2 C785T, CCND1 G870A, IGF1 C/T at intron 2 and G2502T, IL-1A 46-bp VNTR, IL-1R1 C-116T, IL-6 Ins/Del 17C, IL-8 A-278T and C74T, IL- 10 T-819C, LEP A-2548G, SRD5A2 2-bp VNTR, XPD Lys751Gln, and XRCC1 Arg399Gln) and six sets of combined genotype frequencies (IL-1B C-31T and IL-1A C-889T, IL-1B C-31T and IL-1RN 86-bp VNTR, IL-1B C-31T and IL-1R1 C-116T, TNF-A G-308A and TNF-B A252G, SRD5A2 Val89Leu and 2-bp VNTR, and XRCC1 Arg399Gln and XPD Lys751Gln) were reported in this paper for the first time for Japanese. Although microarray technology will produce this kind of information in near future, this is the first document that reports the genotype/allele frequencies among Japanese for an archival purpose.