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Biomedical subjects

Nobuyuki Hamajima

Publications and source records attributed to Nobuyuki Hamajima.

At least 109 records · Page 6Linked to original sources

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.

Adult↗

L-myc genotype is associated with different susceptibility to lung cancer in smokers.

We have shown that L-myc genotype is associated with the risk of esophageal cancer from smoking and heavy drinking. In this study, we have analyzed the relationship between the L-myc genotypes and lung cancer risk from smoking in 191 Japanese lung-cancer patients and 241 non-cancer controls. The odds ratios (ORs) were markedly higher in SS and LS genotypes than in LL genotype; age-sex-adjusted ORs were 3.19, 2.30 and 0.92, respectively. This result suggests that the L-myc polymorphism may affect the induction of lung cancer by smoking. The OR for smoking in SS-genotype patients diagnosed within 2 years was higher than that in other SS patients, suggesting that smoking-related lung cancer in SS genotype might exhibit a poorer prognosis.

Adenocarcinoma↗

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.

Alleles↗

A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung.

The 8-oxoguanine DNA glycosylase (OGG1) repairs DNA by removing 8-hydroxyguanine, a highly mutagenic oxidative DNA adduct. Recently, the gene for OGG1 was cloned and several polymorphisms have been reported. Because environmental carcinogens produce 8-hydroxyguanine residues that potentially cause oncogenic mutations by mismatching to this modified base, the capacity to repair these lesions can be involved in cancer susceptibility. This study investigated the association between OGG1 Ser326Cys polymorphism and risk of the lung adenocarcinoma for Japanese by a prevalent case-control study in Japan. The subjects comprised 138 cases and 241 non-cancer outpatients as controls. OGG1 gene polymorphism was genotyped by a PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. The distribution of OGG1 Ser326Cys genotype among controls (Ser/Ser, 28.3%; Ser/Cys, 49.2%; and Cys/Cys, 22.5%) was not different from that among cases (Ser/Ser, 29.0%; Ser/Cys, 51.4%; and Cys/Cys, 24.0%). The sex-age adjusted odds ratio (OR) was 1.06 with 95% confidence interval (CI) 0.64-1.76 for Ser/Cys genotype and 0.81 with 0.44-1.52 for Cys/Cys genotype. The ORs according to the interval between diagnosis and study enrollment were also examined because the polymorphism was a potential prognostic factor of lung cancer. The ORs of Ser/Cys and Cys/Cys genotypes in the cases less than 3 years after diagnosis were higher than overall ORs; 1.86 (95%CI, 0.91-3.77), and 1.46 (0.64-3.35), respectively. The OR for smoking was not statistically different among genotype, though the sample size was too small to detect even a moderate interaction. This study supported the first study by Sugimura et al (Cancer Epidemiol Biomarkers Prev, 1999; 8: 669-674), that the association of OGG1 Ser326Cys polymorphism was limited for the risk of lung adenocarcinoma.

Adenocarcinoma↗

Association between smoking habits and dopamine receptor D2 taqI A A2 allele in Japanese males: a confirmatory study.

Our previous study showed that A2 allele of dopamine D2 (DRD2) TaqI A polymorphism related to smoking habits, which was opposed to the results of studies for Caucasians. In order to confirm our finding, a similar study was conducted for the first-visit outpatients of Aichi Cancer Center Hospital, who participated in HERPACC-II (Hospital-based Epidemiologic Research Program at Aichi Cancer Center-II). Among consecutive 1,577 first-visit patients between November 2000 and February 2001, 800 patients provided a 7 ml of peripheral blood. Smoking habit data were available for 798 participants. Excluding five participants aged < 20 years or > 80 years, the remaining 793 participants (346 males and 447 females) were analyzed. The DRD2 genotype was determined by a new method, polymerase chain reaction with confronting two-pair primers (PCR-CTPP). In males, current smokers were 35.3% of individuals with A1A1 genotype, 43.1% of individuals with A1A2 genotype, and 57.0% of individuals with A2A2 genotype, while in females, they were 19.6%, 14.6%, and 10.9%, respectively. Age-adjusted odds ratio (OR) of current smoking relative to A1A1 was 1.61 (95% confidence interval, 0.71-3.46) for A1A2 and 2.32 (1.02-5.29) for A2A2 in males, and 0.72 (0.32-1.61) and 0.51 (0.22-1.18) in females, respectively. The present study indicated that Japanese males with A2A2 genotype have a higher risk of being current smokers. No association for Japanese females suggested that female smoking behavior is differently affected in biological and/or psychological manner.

Alleles↗

Aldehyde dehydrogenase 2 (ALDH2) genotype affects rectal cancer susceptibility due to alcohol consumption.

BACKGROUND: Epidemiologic studies have shown the association between alcohol consumption and colorectal cancer, especially for rectal cancer. The alcohol related enzyme encoding gene ALDH2 has polymorphism Glu487Lys, and 487Lys allele is closely linked with phenotypic loss of enzyme activity. MATERIALS AND METHODS: A hospital-based case-control study was conducted with 72 colon and 70 rectal cancer cases and 241 non-cancer controls to evaluate the alcohol consumption and ALDH2 Glu487Lys polymorphism. The logistic regression model was applied to estimate the odds ratios (ORs). RESULT: The crude ORs for Glu/Lys and Lys/Lys genotype relative to Glu/Glu for colon and rectal cancer were not statistically significant. However, with the rectal cancer analysis, the ORs for high alcohol consumption were greater with 487Glu/Lys genotype compared with Glu/Glu, albeit not. CONCLUSIONS: These observations suggested rectal cancer risk might be influenced by ALDH2 gene polymorphism. The prevention effect by alcohol reduction might differ by ALDH2 genotype.

Adult↗

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.

Adult↗

Methionine Synthase Reductase Gene A66G Polymorphism is Associated with Risk of Colorectal Cancer.

A hospital-based case-control study was conducted to evaluate the significance of methionine and folate related polymorphisms, with 72 colon and 70 rectal cancer cases and 241 non-cancer controls. The polymorphisms examined were in the genes for methionine synthase reductase (MTRR A66G), methionine synthase (MTR A2756G) and methylenetetrahydrofolate reductase (MTHFR C677T and A1298C). An unconditional logistic regression model was applied for estimating the odds ratios (ORs) and 95% confidence intervals (CIs). The age-sex adjusted OR for the MTRR GG genotype as compared with the AA and AG genotypes was 2.77 (95% CI: 1.39-5.53, p = 0.004), whereas adjusted ORs for other polymorphisms were not statistically significant. When the ORs for environment factors (smoking, alcohol consumption, body-mass-index, and physical exercise) were calculated according to each polymorphism, no substantial difference was observed except with the MTRR polymorphism. The ORs for the MTRR GG genotype seemed to be modified by the extent of environmental exposure. In conclusion, the present study showed that the GG genotype of MTRR A66G is a risk factor for colorectal cancer in Japanese, while MTHFR and MTR polymorphisms are not. The conclusions, however, need further evaluation in terms of micronutrient status and additional confirmatory studies are required with datasets for various ethnic groups.

Journal Article↗

Allele Frequencies of 25 Polymorphisms Pertaining to Cancer Risk for Japanese, Koreans and Chinese.

Allele frequencies are rather constant among different ethnic groups in many genetic polymorphisms, but some polymorphisms vary in the allele frequency depending on the time when the germ-line base exchanges occurred in the history of humans and on the adaptability of the phenotypes to given environment. This review documented the allele frequencies of polymorphisms pertaining to cancer risk for Japanese, Koreans, and Chinese. Twenty-five polymorphisms of 21 genes whose allele frequencies were available for at least two out of the three ethnic groups were selected. They were ALDH2 Glu487Lys, COMT Val158Met, CYP1A1 MspI and Val/Ile, CYP1B1 Leu432Val, CYP2E1 RsaI, CYP17 T-34C, ER C975G, GSTM1, GSTT1, GSTP1 Ile105Val, IL-1B C-511T, IL-1RN 86-bp VNTR (variable number of tandem repeats), MTHFR C677T and A1298C, NAT1, NAT2, NQO1 Pro187Ser, OGG1 Ser326Cys, p21 Ser31Arg, p53 Arg72Pro, TNF-A G-308A and G-238A, and XRCC1 Arg194Trp and Arg399Gln. The allele frequencies were found for 24 in Japanese, 16 in Koreans, and 24 in Chinese. All of the polymorphisms had similar allele frequencies for these ethnic groups, except the following polymorphisms; ALDH2 Glu487Lys whose Lys allele was more common for Japanese and Taiwanese, COMT Val158Met whose Met allele was more common for Japanese, and NAT2 rapid/slow whose slow alleles were more common for Chinese. When compared with the allele frequencies among Caucasians, the following minor alleles were more frequent among Japanese/Koreans/Chinese; ALDH2 478Lys, CYP1A1 m1 and m2, CYP2E1 c2, ER 975G, GSTT1 null, NAT1 *10, NQO1 187Ser, OGG1 326Cys, p21 31Arg, and XRCC1 194Trp, and less frequent in COMT 158Met, GST-P1 105Val, IL-1RN non-4R, MTHFR 1298C, and TNF-A -308A. The differences in genetic background may affect the impact on the lifestyle factors and/or genotypes examined in epidemiological studies. However, the influences of the variations in the allele frequency seemed to be limited among Japanese, Koreans, and Chinese. The substantial differences in the allele frequency from Caucasians could modify the influences of lifestyle factors and polymorphism genotypes, resulting in the inconsistent results of epidemiologic studies.

Journal Article↗

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.

Journal Article↗

Helicobacter Pylori Seropositivity, the Interleukin 1B Polymorphism, and Smoking among First-visit Outpatients.

Our previous studies of 241 re-visit outpatients in the Helicobacter pylori (HP) eradication program (HPE) of Aichi Cancer Center Hospital (Jpn J Cancer Res 2001;92:383-389 ) and of 462 health checkup examinees (HCE) in Nagoya (Jpn J Public Health 2001;48:604-612) found a significant association between HP seropositivity and the Interleukin 1B (IL-1B) C-31T genotype, especially among current smokers. This study aimed to confirm the association for 547 first-visit outpatients (277 males and 270 females) of Aichi Cancer Center Hospital aged 40 to 79 years. Samples were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP), the same method as that used in the previous studies. Sex-age-adjusted odds ratio (aOR) was 1.32 (95% confidence interval, 0.84-2.08) for CT genotype and 1.35 (0.84-2.08) for TT genotype. The aOR was higher in never smokers (aOR=1.69, 0.86-3.32 for TT genotype) than in current smokers (aOR=1.01, 0.34-2.98 for TT genotype). The obtained aORs for TT genotype were inconsistent to those in our previous studies; aOR=2.46 (1.06-5.74) for 241 HPE, aOR=1.74 (1.05-2.89) for 462 HCE, aOR=22.9 (1.97-266) for 55 HPE current smokers, and aOR=4.62 (0.94-22.7) for 67 HCE current smokers. Since the 95% confidence intervals of aORs for TT genotype from the three study subjects overlapped, the inconsistent findings could be due to random errors. Alternatively, there might be other effect modifiers for the association with the polymorphism. Further studies will be required to elucidate the causes of the observed inconsistent findings.

Journal Article↗

Valid Responses to ABO Blood Type Question in Self-reporting Questionnaire.

This paper reports the sensitivity and specificity of self-reported ABO blood type. Subjects were 283 outpatients who participated in Helicobacter pylori eradication program at Aichi Cancer Center Hospital. Excluding seven patients, an ABO blood test was successfully conducted for 276 participants (133 males and 143 females). Only three participants answered their blood type differently from the results of the blood test; one A-type male answered to be with AB type, one B-type male with AB type, and one AB-type male with A type. Nine participants stated that they did not know their ABO blood type. The sensitivity was 98.7% (95% confidence interval, 92.8-100.0%) for 75 O-type individuals, 96.1% (90.3-98.9%) for 102 A-type individuals, 92.9% (84.1-97.6%) for 70 B-type individuals, and 93.1% (77.2-99.2%) for 29 AB-type individuals, when the nine individuals were included. The specificity was more than 99% for any blood type. These findings revealed that self-reported ABO blood type is highly valid for epidemiologic studies.

Journal Article↗

A Large-scale Follow-up Study of Smokers Visiting Medical Facilities in Japan.

In order to determine smoking cessation rates among those who visit medical facilities in Japan, a large-scale follow-up study was conducted. Subjects were self-reported smokers who visited a cancer hospital, a general hospital, or one of four health checkup facilities in 1997-98. Their smoking habits were followed by two postal surveys. The first was two months after the visit to hospital or attendance at a health checkup screening, and the second was after one year. In total, 3,552 smokers participated in the present study; 1,131 first visit outpatients at a cancer hospital, 214 first visit outpatients at a general hospital, and 2,207 examinees at four health checkup facilities. The response rate for the first follow-up varied from 57.3% to 80.2% of the eligible participants in the six facilities, and that for the second from 50.0 to 67.1%. When non-respondents were classified as non-quitters, the cessation rate two months after their participation was 11.7% (95% confidence interval, 7.4-16.0%) for the general hospital and 2.7% (2.1-3.5%) for the four health checkup facilities, and those after one year were 9.8% (6.2-14.6%) and 6.0% (5.1-7.1%), respectively. In the cancer hospital, the rate for self-reported cancer patients was 74.6% (68.5-80.0%) after two months and 51.3% (44.7-57.9%) one year later. The smoking cessation rate was thus smaller in the health checkup examinees than in the patients. Outpatients seemed to be more amenable to smoking cessation, and therefore may constitute a more appropriate target for cessation programs.

Journal Article↗

Gene-environment Interactions and Polymorphism Studies of Cancer Risk in the Hospital-based Epidemiologic Research Program at Aichi Cancer Center II (HERPACC-II).

Genetic polymorphisms may modify the effects of environmental risk factors on cancer occurrence. We have recently launched a comprehensive epidemiologic project, HERPACC II (Hospital-based Epidemiologic Research Program at Aichi Cancer Center II), including both lifestyle and polymorphism data, following HERPACC-I which solely concentrated on lifestyle data. As of April 2001, about 3000 samples of DNA are being stored to conduct case-control studies. Genotyping of 46 polymorphisms has been conducted at the laboratory of the Division of Epidemiology and Prevention. Twelve case-control studies and two papers on a new PCR method, PCR-CTPP (polymerase chain reaction with confronting two-pair primers), have been accepted for publication. Significant findings in Japanese were found for 1) gene-environment interaction for esophageal cancer between heavy drinking and aldehyde dehydrogenase 2 (ALDH2), 2) malignant lymphoma risk with methylenetetrahydrofalate reductase (MTHFR) and methionine synthase (MS), 3) interactions between smoking and two polymorphisms, interleukin 1B (IL-1B) and myeloperoxidase (MPO) for Helicobacter pylori infection, and 4) smoking habits with dopamine receptor D2 (DRD2) and IL-1B. Further studies on interactions with polymorphisms will continue to be conducted for Japanese, using larger sizes of samples.

Journal Article↗

Genotype Frequencies of Cyclooxygenease 2 (COX2) Rare Polymorphisms for Japanese with and without Colorectal Cancer.

Cyclooxygenase 2 (COX2) is an inducible enzyme synthesizing prostaglandins from arachidonic acid, which is thought to play an important role in colorectal carcinogenesis. Since the COX2 polymorphisms, if functional, may modify the carcinogenesis pathway, the associations between the reported polymorphisms and colorectal cancer risk were examined in a hospital-based case-control study. Six polymorphisms of the gene encoding COX2 were genotyped for 241 non-cancer individuals (controls) and 148 colorectal cancer patients (74 colon cancer, 73 rectal cancer, and 1 colorectal cancer date, 22 polymorphisms including the above six have been reported for COX2. The other polymorphisms remain to be examined.

Journal Article↗

Subtle Instruction to Quit Smoking May be Efficacious for Certain Smokers.

There is no doubt that well-designed advertisements influence behavior of consumers, though the effects may vary depending on the advertisement targets. This is particularly true of tobacco advertisements. Deliberately coined words and images can effectively lead persons, especially youth, to acquiring smoking habits. However, demonstrating the effects of advertisements behavioral changes (eg. starting smoking and quitting smoking) in a framework of research is generally difficult, and epidemiologists tend to adopt a conservative stance against the association between such subtle messages and behavioral changes. Although we understand this stance as epidemiologists, we dare to report here a potential effect of a seemingly trivial message against smoking as observed in a follow-up study of smokers.

Journal Article↗