Masahiro Kihara

CYP1A1 T3801 C polymorphism and lung cancer: A pooled analysis of 2,451 cases and 3,358 controls

CYP1A1 is involved in the metabolism of benzopyrene, a suspected lung carcinogen; it is therefore conceivable that genetically determined variations in its activity modify individual susceptibility to lung cancer. The role of the CYP1A1 MspI polymorphism in lung cancer has been widely studied but has not been fully clarified. We have included 2,451 cases and 3,358 controls in a pooled analysis of 22 case‐control studies on CYP1A1 and lung cancer risk. We found a clear association between the CYP1A1 homozygous MspI restriction fragment length polymorphism (RFLP) and lung cancer risk in Caucasians (age‐ and gender‐adjusted odds ratio = 2.36; 95% confidence interval 1.16–4.81); other associations were weaker or not statistically significant. The association with the homozygous variant was equally strong for squamous cell carcinomas and adenocarcinomas among Caucasians. We analyzed the risk by duration of smoking: for Caucasian subjects with the MspI RFLP combined variants (homozygotes plus heterozygotes), the increase in the risk of lung cancer was steeper than among the individuals with the homozygous reference allele. Our analysis suggests that Caucasians with homozygous variant CYP1A1 polymorphism have a higher risk of lung cancer. The data were more consistent among Caucasians, with a strong association between the homozygous variant in both squamous cell carcinomas and adenocarcinomas, and a stronger association in men than in women. The analyses were more inconsistent and failed to reach statistical significance in Asians. This observation might be due to design specificities or unknown effect modifiers in the Asian studies.

Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States).

Objective: Cytochrome P450 1A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Much interest has focused on a polymorphism in exon 7 of the CYP1A1 gene which has been associated with a more inducible form of the enzyme. However, past results of its association with lung cancer have been inconsistent, especially in Caucasians. We carried out a pooled analysis of the data submitted to the Genetic Susceptibility to Environmental Carcinogens (GSEC) database to further investigate this association and, especially, to examine the modifying effects of smoking status and race. Methods: The data set used in this analysis included 11 studies and a total of 1950 cases and 2617 controls. Both fixed- and random-effects, meta-analysis models were used to investigate heterogeneity among studies. Because no clear heterogeneity was found, a pooled analysis was conducted using unconditional logistic regression. Results: The pooled odds ratio for subjects heterozygous and homozygous for the exon 7 polymorphism was 1.15 (95% confidence interval: 0.95–1.39) and 1.54 (95% CI: 0.97–1.46), respectively (p for gene-dosage effect: 0.03). This association was stronger for squamous cell carcinoma (SCC) than adenocarcinoma, and appeared to be stronger in Caucasians than Asians (p for interaction: 0.03). Statistically significant interactions were also detected for smoking status and sex, with the effect of the polymorphism being stronger in never-smokers and in females. Conclusions: The present data suggest that the CYP1A1 exon 7 polymorphism may confer an increased risk of lung cancer, particularly of SCC, and especially in never-smokers and in women. These interactions need to be confirmed when additional studies are available for pooling.

High prevalence of HIV infection associated with incarceration among community-based injecting drug users in Tehran, Iran

Objectives: To determine the prevalence and correlates of HIV-1 infection among community-based injecting drug users (IDUs) in Tehran, Iran. Methods: In October 2004, 213 IDUs were recruited from a drop-in center and its neighboring parks and streets in Tehran. Participants were interviewed using a structured questionnaire regarding their sociodemographics and HIV risk characteristics, and specimens of oral mucosal transudate were collected and tested for HIV-1 antibodies. Data were analyzed using &khgr;2 and multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: The prevalence of HIV-1 infection was 23.2% (48 of 207) among male injecting drug users. In the multivariable analysis, a history of shared drug injection inside prison (OR, 2.45; 95% CI, 1.01-5.97) and that of multiple incarcerations (OR, 3.13; 95% CI, 1.08-9.09) were associated with significantly higher prevalence of HIV-1 infection. Conclusions: The prevalence of HIV-1 infection has reached an alarming level among IDUs in Tehran, with incarceration-related exposures revealed to be the main correlates of HIV-1 infection. Urgent and comprehensive harm reduction programs for drug users in prison and those in the community in Tehran are of prime importance to prevent further transmission of HIV infection.

Early initiation of sexual activity: a risk factor for sexually transmitted diseases, HIV infection, and unwanted pregnancy among university students in China

BackgroundTo explore any association between the timing of the initiation of sexual activity and sexual behaviors and risks among university students in China.MethodsData were derived from a cross-sectional study on sexual behavior among university students conducted in Ningbo municipality, China, at the end of 2003. Students completed a self-administered, structured questionnaire. Of 1981 sexually active male students, 1908 (96.3%) completed the item for timing of the initiation of sexual activity and were included in bivariate trend analyses and multiple logistic regression analyses to compare the association between this timing and sexual behavior and risks.ResultsMale early sexual initiators had a significantly higher risk profile, including a significantly higher proportion reporting non-regular partners (i.e., casual or commercial partners), multiple partners, diagnosis with a sexually transmitted disease (STD), partner history of pregnancy, partner history of induced abortion, and less condom and oral contraceptive use, compared with late initiators. Multivariate analyses confirmed the increased likelihood of these risks in early initiators versus late initiators, other than partner type during the last year.ConclusionOur results showed that, compared to late initiators, people who initiated sexual activity early engaged in more risky behaviors that could lead to elevated risks of unwanted pregnancies and STDs or human immunodeficiency virus infection. Sex-education strategies should be focused on an earlier age, should include advice on delaying the age of first sexual activity, and should target young people who continue to take sexual risks.

Prevalence of and factors associated with HIV-1 infection among drug users visiting treatment centers in Tehran, Iran

Objectives:This study was conducted to identify the prevalence of and potential risk factors for HIV-1 infection among drug users visiting drug treatment centers in Tehran, Iran. Design:Cross-sectional quantitative study. Methods:Between October 2003 and May 2004, drug users who visited three public drug treatment centers in Tehran were interviewed and information about their sociodemographics, drug use characteristics, incarceration history, sexual history, and HIV/AIDS knowledge and risk perception were collected. Specimens of oral mucosal transudate were then collected from participants to be tested for HIV-1 antibodies. Logistic regression analysis was conducted on the association between the demographic and behavioral factors with HIV-1 infection. Results:Overall, 611 (588 male and 23 female) drug users participated in the study. Among male injectors with HIV-1 prevalence of 15.2%, a history of shared injection inside prison [adjusted odds ratio (OR), 12.37; 95% confidence interval (CI), 2.94–51.97] was the main factor associated with HIV-1 infection. Among those who reported no history of injecting drug use, HIV-1 prevalence was 5.4%, and lack of condom use during sex was significantly associated with the infection (adjusted OR, 3.42; 95% CI, 1.25–9.36). Conclusions:HIV-1 infection is already prevalent among drug users in Tehran, Iran and shared injection inside prison has been revealed to be a particular risk factor for HIV-1 infection among injecting drug users. Harm reduction programs which have been started in Iran should be urgently expanded particularly in correctional settings and strengthened by condom use promotion to prevent sexual acquisition or transmission of HIV-1 among drug users.

Needle and syringe sharing practices of injecting drug users participating in an outreach HIV prevention program in Tehran, Iran: A cross-sectional study

HIV infection rates have reached epidemic proportions amongst injecting drug users (IDUs) in Iran. Although a number of community-based interventions have being implemented in the country, there is little information on the risk behaviors of IDU participants in these programs. This cross-sectional report aimed to compare the risk behaviors of injecting drug users with differential exposure rates to an HIV outreach program in Tehran, Iran. Results indicated that shared use of needle/syringe in the past month was significantly lower among IDUs who received estimated ≥ 7 syringes per week than those who did not [adjusted odds ratio (OR) = 14.36, 95% confidence interval (CI) 2.30–89.56]. While the effectiveness of this outreach program needs further evaluation through a longitudinal investigation, our preliminary findings suggest that the outreach program in Tehran may have been beneficial in reducing direct sharing among those who received more than several needles/syringes from the program.

Sexual behavior and awareness of Chinese university students in transition with implied risk of sexually transmitted diseases and HIV infection: A cross-sectional study

BackgroundThe vulnerability of young people to HIV and the recent emergence of the HIV epidemic in China have made it urgent to assess and update the HIV/STD risk profile of Chinese young people.MethodsA self-administered questionnaire survey with cross-sectional design was conducted among 22,493 undergraduate students in two universities in Ningbo, China. Bivariate trend analysis and multiple logistic regression analysis were used to compare sexual behaviors and awareness between grades.ResultsOf respondents, 17.6% of males and 8.6% of females reported being sexually active. Condom was reported never/rarely used by 35% of sexually active students in both genders in the previous year. Pregnancy and induced abortion had each been experienced by about 10% of sexually active female students and the female partners of male students, and about 1.5% of sexually active students of both genders reported being diagnosed with an STD. Multivariate analysis revealed that students in lower grades, compared to those in higher grades, were more likely to have become sexually active before university, to have become aware of sex before high school, and to have been exposed to pornographic media before the age of 17 years, and for sexually active respondents of both genders, to have engaged in sex without using a condom.ConclusionSexual behaviors of Chinese university students are poorly protected and sexual behaviors and awareness may have been undergoing rapid change, becoming active earlier and more risky. If this trend continues, vulnerable sexual network will grow among them that allow more expansion of sexually transmitted diseases and HIV.

Lung cancer risk of the GSTM1 null genotype is enhanced in the presence of the GSTP1 mutated genotype in male Japanese smokers

The potential interaction of GSTM1 and GSTP1 genotypes in pulmonary carcinogenesis was assessed in 382 male Japanese lung cancer patients (127 squamous cell carcinoma, 78 small cell carcinoma, 177 adenocarcinoma) and 257 controls. In smokers (358 cases, 184 controls) the GSTM1 null genotype was more distributed in individuals with at least one GSTP1 mutant allele compared to those without, in lung cancer patients (69.5% vs.53.2%) but not in controls (48.0% vs. 48.5%). No such relationship was detected in non-smokers (24 cases, 73 controls). The estimated relative risk of the GSTM1 null genotype for lung cancer was 2.58 (95%CI = 1.26-5.30) in smokers with the GSTP1 mutant allele while it was 1.17 (95%CI = 0.77-1.79) in those without, suggesting that mutated GSTM1 and GSTP1 genotypes interact to potentiate the risk of lung cancers in Japanese smokers.

GSTM1 gene polymorphism as a possible marker for susceptibility to head and neck cancers among Japanese smokers

Increased risk of lung cancer has been reported in individuals with glutathione S-transferase M1 (GSTM1) gene deletion, with limited evidence for head and neck (HN) cancer. Here, we report the results of a case-control study in Japanese HN cancer patients (n = 158) and community controls (n = 174). GSTM1 null genotype (GSTM1(-)) was distributed more in smoker patients than in control subjects (56.7% vs. 48.5%) but not in non-smoker patients (48.3%). In smokers, GSTM1(-) was detected at increased frequency in non-larynx cancer (62.7%, odds ratio 1.77, 95% CI 1.04-3.01) but not in larynx cancer (48.1%). In larynx cancer GSTM1(-) was presented at higher frequency in patients < 60 years old than in those > or = 60 years old (78.6% vs. 36.8%). These findings suggest that the GSTM1 gene polymorphism potentially modifies the risk for HN cancer depending on smoking history, the region of cancer and age.

Substance use and sexual behaviours of Japanese men who have sex with men: A nationwide internet survey conducted in Japan

BackgroundJapanese men who have sex with men (MSM), especially those living in large metropolitan areas such as Tokyo and Osaka, are facing a growing HIV/AIDS epidemic. Although the Internet is used as a new venue for meeting sex partners, it can also serve as a useful research tool for investigating the risk behaviours of Japanese MSM. This Internet survey explored the extent of substance use and its association with sexual risk behaviours among Japanese MSM.MethodsBetween 28 February 2003 and 16 May 2003 MSM were recruited through 57 Japanese gay-oriented Web sites, gay magazines, and Internet mailing lists. Participants completed a structured questionnaire anonymously through the Internet.ResultsIn total, 2,062 Japanese MSM completed the questionnaire. The average age of participants was 29.0 years and 70.5% identified as gay, 20.8% as bisexual, and 8.7% as other. Overall, 34.5% reported never using a substance, 45% reported ever using one type of substance (lifetime reported single substance users), and 19.6% had used more than 1 type of substance (lifetime reported multiple substance users) in their lifetimes. The substances most commonly used were amyl nitrite (63.2%), 5-methoxy-N, N-diisopropyltryptamine (5MEO-DIPT) (9.3%), and marijuana (5.7%). In the multivariate analysis, unprotected anal intercourse, having had 6 or more sexual partners, visiting a sex club/gay venue in the previous 6 months, a lower education level, and being 30 to 39 years of age were associated with both lifetime single and lifetime multiple substance use. Lifetime reported multiple substance use was also correlated with having a casual sex partner, having symptoms of depression, being diagnosed as HIV-positive, and greater HIV/AIDS-related knowledge.ConclusionThis is the first Internet-based research focused on the sexual and substance use behaviours of MSM in Asia. Our findings suggest a compelling need for prevention interventions to reduce HIV risk-related substance use behaviours among Japanese MSM. The results also suggest that the Internet is potentially a useful tool for collecting behavioural data and promoting prevention interventions among this population.