Glutathione S-transferase M1 and susceptibility to nasopharyngeal carcinoma.

Genetic polymorphisms for enzymes that metabolize tobacco smoke have been reported to determine susceptibility to several smoking-related cancers, including cancers of the lung, bladder, and head and neck. Glutathione S-transferase M1 (GSTM1) detoxifies benzo(a)pyrene and other carcinogens in tobacco smoke. Approximately 50% of Caucasians lack the GSTM1 gene. Because the most common type of nasopharyngeal cancer (NPC), squamous cell carcinoma, is related to smoking, we sought to determine whether GSTM1 is associated with risk for NPC. Cases (n = 83) were from a population-based study conducted from 1987 to 1993 at five cancer registries in the United States. Random-digit dialing controls (n = 114) were matched to the cases for age, sex, and registry. Subjects participated in a phone interview and blood draw. Absence of GSTM1 was associated with increased risk for NPC (odds ratio = 1.9, 95% confidence interval = 1.0-3.3 for all cases; and odds ratio = 1.7, 95% confidence interval = 0.8-3.5 for squamous cell cases). This relationship was not modified by smoking history, but stronger relationships between glutathione S-transferase and NPC were suggested among subjects who used alcohol more frequently than others, older subjects (50 or more years of age), and women relative to men. These data indicate that absence of GSTM1 moderately increases risk for NPC and add to growing evidence that GSTM1 is a determinant of risk for several smoking-related cancers.

Nasopharyngeal cancer in a low-risk population: defining risk factors by histological type.

Nasopharyngeal cancer (NPC) is a major public health problem in parts of Southeast Asia and North Africa, but is rare among whites and blacks. Although infection with the EBV and genetic susceptibility appear to play large roles in high-incidence populations, migrant studies suggest that environmental factors may also be important. Aside from the high risks associated with ingestion of salted fish, surprisingly few other risk factors have been established from studies in endemic areas. We studied a low-incidence population to determine whether tobacco use, alcohol consumption, and certain medical conditions and treatments are related to NPC and to examine variations in risk by histology. We reasoned that new relationships might be best identified in the absence of strong causal pathways, such as intake of preserved foods and genetic susceptibility. A population-based case-control study was conducted from 1987 to 1993 at five cancer registries in the United States: western Washington, metropolitan Detroit, Connecticut, Iowa, and Utah. Controls were identified by random digit dialing and frequency matched to the gender and age distribution of cases at each registry. Telephone interviews were completed by 231 cases and 246 controls. We observed a strong dose-response relationship between cigarette smoking and risk of differentiated squamous cell carcinoma (test for trend, P < .001). The highest risk [odds ratio (OR), 6.5; 95% confidence interval (CI), 2.0-21.3] occurred among current smokers with a history of more than 60 pack-years. In contrast, there was no evidence that undifferentiated or nonkeratinizing carcinomas were associated with cigarette smoking. Similarly, a significant increase in risk was observed for the heaviest alcohol consumers (21 or more drinks/week) only for differentiated squamous cell carcinomas (OR, 2.9; 95% CI, 1.2-6.9). The associations with cigarettes and alcohol appeared to be stronger among persons 50 years or older. There was a suggestion that diagnosis with infectious mononucleosis (a marker of late infection with EBV) is linked with decreased NPC risk (OR, 0.4; 95% CI, 0.1-1.1). This report indicates that over two-thirds of differentiated squamous cell NPC cases arising in older persons in the United States can be accounted for by cigarettes and alcohol, but leaves unexplained cases arising in the young and carcinomas of undifferentiated or nonkeratinizing histology. Future studies of NPC need to take into account histology and age in evaluating these and other environmental and genetic risk factors.

Associations between human leukocyte antigen type and nasopharyngeal carcinoma in Caucasians in the United States.

A genetic component to nasopharyngeal carcinoma (NPC) has been suggested by associations of the malignancy with human leukocyte antigens (HLAs) in Southern Chinese populations, among which NPC is a major cancer. Data from other races are inconclusive. We have investigated associations between NPC and HLA antigens at the HLA-A, B, C, and DQ loci and alleles at the DRB1 locus in a population-based, multicenter investigation in the United States. Data from 82 cases and 140 controls are presented, making this the largest study population analyzing data from Caucasians to date. HLA frequencies from study cases were also compared with external control groups from the 11th International Histocompatibility Workshop and the National Marrow Donor Program. Logistic regression methods were used to investigate the effects of the joint occurrence of multiple HLA types and to assay for differences in HLA-associated risk in different age groups. A meta-analysis was undertaken to compare and summarize our results with previously published findings. The meta-analysis found a protective association with A2 antigen in non-Chinese [odds ratio (OR), 0.63; P < 0.001], a protective association with A11 across all races (OR, 0.54; P < 0.001), and an increased risk associated with B5 in Caucasians (OR, 2.81; P < 0.001). The present study also found independent associations, in a logistic regression model, between NPC and DRB1*1501 (OR, 0.33), DRB1*0405 (OR, 7.57), and Cw3 (OR, 0.42), although these data must be interpreted cautiously due to multiple-testing considerations. Associations were found to be more pronounced in younger patients for A2, A11, A28, B8, and B51.

Smoking cessation among high school seniors.

BACKGROUND: Effecting smoking cessation among adolescents provides an opportunity to reduce smoking levels among teens and among the adults those teens are soon to become. Better understanding of high school students' cessation behavior is needed to inform the development of effective strategies to support teen quitting. METHODS: Data from 1,210 established smokers among 6,427 12th graders from rural and suburban communities in Washington State were used to determine the frequency of a declared intention to quit, one or more quit attempts in the past year, ongoing quitting, and the attainment of long-term cessation. Logistic regression models investigated the association of these outcomes with the extent of peer smoking, age of becoming a regular smoker, sex, and grade point average (GPA). RESULTS: A serious intention to quit was declared by 67% of established smokers, and at least one attempt to quit was made in the past 12 months by 60%. However, only 21% of those who had attempted to quit in the past year were still abstaining at the time of the survey, and overall, merely 3% had achieved cessation beyond 12 months. The likelihood of success of quit attempts was strongly dependent on the extent of smoking among peers. Subjects who had become regular smokers at the youngest ages were more likely to undertake a quit attempt than those who started older. Females were less successful than males in attaining ongoing abstinence. Cessation behavior showed no clear association with students' GPA. CONCLUSIONS: A high fraction of high school smokers want to quit, but are unsuccessful in doing so. Thus, there is a need for programs to provide cessation skills to young smokers already motivated to quit.

Evaluating the risks of cesarean section: low Apgar score in repeat C-section and vaginal deliveries.

Data from Washington State birth certificates from 1980-83 were used to estimate excess risk to the infant delivered via repeat cesarean section independently of any risk associated with the indication for the procedure. Using a case-control design, we compared the method of delivery of all infants with low (0-6) five-minute Apgar scores born to multiparous mothers after uncomplicated pregnancies and births to that of similar infants with a high score (7-10), frequency matched by birthweight. Of the 1,030 infants with low Apgar score, 127 (12.3 per cent) were delivered via repeat cesarean section, in contrast to 98 (9.8 per cent) of 998 controls with high Apgar score. In a regression model controlling for birthweight, gestational length, maternal age, and income the relative risk was 1.29 (95% confidence interval 0.97, 1.72). Excess risk was highest among babies of normal (2500-4000 grams) birthweight. While a number of limitations inherent in the source of data require cautious interpretation of these results, we conclude that some excess risk of low Apgar score may be associated with repeat cesarean section procedures.

Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the United States.

Population-based incidence data on nasopharyngeal carcinomas (NPC) from the Surveillance, Epidemiology and End Results program in the United States were examined for the years 1973-1986. The 1,645 cases showed incidence rates varying according to ethnic origin, with chinese having the highest, followed by Filipinos, Blacks and Whites. In females the incidence was about half of that seen in males, in each of these groups. There was no evidence of changes in incidence rates during the study period. An analysis of survival with NPC was undertaken using hazard function regression models to allow for control of multiple variables. Survival was found to be independently influenced by age and stage at diagnosis, histologic type, grade and sex. Significant ethnic differences in survival remained after adjustment for these factors, with Chinese surviving longest followed by Filipinos, Whites and Blacks. These difference in survival remained after control for the variation in population-wide mortality rates associated with age, ethnicity, sex and calendar year. We present evidence that survival has improved for this disease over time.

A protective association between the HLA-A2 antigen and nasopharyngeal carcinoma in US Caucasians.

Analyzing data from Caucasians participating in a multicentered population-based case-control study of nasopharyngeal carcinoma and HLA type in the US, we found persons with the A2 antigen to have a significantly lower risk than those with other antigens at the A locus [odds ratio (OR), 0.46; 95% confidence interval (CI), 0.21-0.96]. The protective association was stronger among presumptive homozygotes for A2. Similar results were obtained when cases were compared with US Caucasians typed either as part of the Collaborative Transplant Study, or by the 9th International Histocompatibility Workshop. These results are supported by a statistical summary of odds ratios for A2 from a number of previous studies in non-Chinese (summary OR, 0.69; 95% CI, 0.54-0.88). The odds ratio for patients with squamous-cell carcinomas was 0.56; among 7 patients with undifferentiated tumors the OR was 0.14. Results from in vitro studies of immune response to Epstein-Barr virus have found that the HLA-A2 antigen efficiently presents the EBV gene product LMP-2, which has been detected in NPC tumor cells. This offers a rationale for the observed protective association between the HLA-A2 antigen and nasopharyngeal carcinoma.

Predicting adolescent smoking: a prospective study of personality variables.

OBJECTIVE: We investigated how personality variables measured at 5th grade predict daily smoking in 12th grade. METHODS: A group of 3130 fifth graders was assessed for a propensity toward Rebelliousness, Risk Taking, Problem Helplessness, Affect Regulation, and Early Maturation and susceptibility to Peer Compliance and Peer Approval. Daily smoking status was determined for 94.7% of them 7 years later, in 12th grade. RESULTS: Rebelliousness and Risk Taking were the most significant predictors of smoking. There was no statistical evidence that the extent of prediction depended on gender or history of early smoking. No predictive evidence was seen for the other personality measures, including those describing susceptibility to peer influences. CONCLUSIONS: These results show that propensity toward rebelliousness and risk taking in childhood predicts adolescent smoking. They suggest that smoking prevention programs would do well to address the needs and expectations of rebellious and risk-taking youth.