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.

Helicobacter pylori seropositivity and IL-1B C-31T polymorphism among Japanese Brazilians.

We reported previously that anti-Helicobacter pylori antibody seropositivity (HP+) had an association with interleukin 1B (IL-1B) C-31T genotype, especially among smokers. This study examined the association for Japanese Brazilians. In this cross-sectional study, voluntary participation was announced through Japanese Brazilian communities in Sao Paulo, Curitiba, Mogi das Cruzes, and Mirandopolis; 963 Japanese Brazilians (399 males and 564 females) aged 33-69 years participated. Lifestyle data and peripheral blood were collected. An anti-HP IgG antibody test and genotyping for IL-1B C-31T and IL-1RN 86 bp VNTR were independently conducted. The genotype frequency of the IL-1B polymorphism among 947 individuals was 23.9% for C/C genotype, 45.6% for C/T genotype, and 30.5% for T/T genotype. Sex-age-adjusted odds ratio (aOR) of HP+ was 1.30 (95% confidence interval, 0.94-1.81) for C/T genotype and 1.45 (1.02-2.07) for T/T genotype relative to C/C genotype. The aOR for 127 current smokers was 2.45 (0.91-6.55) for C/T and 3.49 (1.17-10.46) for T/T, while that for 667 never smokers was 1.21 (0.82-1.78) and 1.36 (0.90-2.05), respectively. The corresponding figures were 2.42 (1.16-5.02) and 3.00 (1.33-6.78) for 226 current drinkers, and 1.21 (0.82-1.78) and 1.36 (0.90-2.05) for 667 non-drinkers. The difference in the OR was observed for milk consumption, salty pickled vegetable eating, and physical exercise practice. 4/4 Genotype of IL-1RN 86 bp VNTR was 84.8%, and had no association with the HP seropositivity. The observed association between HP+ and IL-1B -31TT indicated that the genetic trait also influences the susceptibility to HP for Japanese in Brazil.

Why is the Impact of Genetic Polymorphisms on the Smoking Habit not Consistent? Possibly Diluted Association with the Interleukin-1B C-31T Polymorphism in Japanese Brazilians.

The smoking habit is influenced by culture, psychological traits and physical factors. Recent studies on genetic polymorphisms have demonstrated that functional polymorphisms pertaining to neurotransmitters may affect smoking behavior, as well as psychological parameters and diseases. Our recent study demonstrated the interleukin (IL)-1B gene encoding IL-1b, a pro-inflammatory cytokine, to be associated with smoking; Japanese with the IL-1B C-31T T/T genotype, an inflammation-prone trait, were less likely to be smokers than those with IL-1B C-31T C/C (J Epidemiol 2001;11:120-125). This indicates that genetically determined biochemistry may also be an important factor for smoking behavior. We have investigated this association in another population, 963 Japanese Brazilians (399 males and 564 females) aged 33-69 years from Curitiba, Mogi das Cruzes, and Mirandopolis in Brazil. Current smokers were 15.3% among males and 11.6% among females. The sex-age-adjusted odds ratio (OR) for the polymorphism in males was around unity. In females, the adjusted OR of being current smokers vs. non-current smokers was 0.68 (95% confidence interval, 0.32-1.45) for the T/T genotype relative to the C/C genotype, and the adjusted OR of being ever smokers vs. never smokers was 0.85 (0.46-1.58). Significant reduction in the OR was not observed for either males or females with the T/T genotype. Although the inconsistent result could be caused by random variation, effect dilution caused by incorporation of a group with a smoking-free culture is a possible reason for the apparent anomaly. The effect of dilution may thus have to be taken into consideration, especially for studies on the smoking habit and genetic polymorphisms.