Phthalates impact on the epigenetic factors contributed specifically by the father at fertilization.

BACKGROUND: Preconception exposure to phthalates such as the anti-androgenic dibutyl-phthalate (DBP) impacts both male and female reproduction, yet how this occurs largely remains unknown. Previously we defined a series of RNAs expressly provided by sperm at fertilization and separately, and in parallel, those that responded to high DBP exposure. Utilizing both populations of RNAs, we now begin to unravel the impact of high-DBP exposure on those RNAs specifically delivered by the father. RESULTS: Enrichment of RNAs altered by DBP exposure within the Molecular Signature Database highlighted cellular stress, cell cycle, apoptosis, DNA damage response, and gene regulation pathways. Overlap within each of these five pathways identified those RNAs that were specifically (≥ fivefold enriched) or primarily (≥ twofold enriched) provided as part of the paternal contribution compared to the oocyte at fertilization. Key RNAs consistently altered by DBP, including CAMTA2 and PSME4, were delivered by sperm reflective of these pathways. The majority (64/103) of overlapping enriched gene sets were related to gene regulation. Many of these RNAs (45 RNAs) corresponded to key interconnected CRREWs (Chromatin remodeler cofactors, RNA interactors, Readers, Erasers, and Writers). Modeling suggests that CUL2, PHF10, and SMARCC1 may coordinate and mechanistically modulate the phthalate response. CONCLUSIONS: Mediated through a CRREW regulatory network, the cell responded to exposure presenting stressed-induced changes in the cell cycle-DNA damage-apoptosis. Interestingly, the majority of these DBP-responsive epigenetic mediators' direct acetylation or deacetylation, impacting the sperm's cargo delivered at fertilization and that of the embryo.

Investigating temporal changes in hybridization and introgression in a predominantly bimodal hybridizing population of invasive sika (Cervus nippon) and native red deer (C. elaphus) on the Kintyre Peninsula, Scotland.

We investigated temporal changes in hybridization and introgression between native red deer (Cervus elaphus) and invasive Japanese sika (Cervus nippon) on the Kintyre Peninsula, Scotland, over 15 years, through analysis of 1513 samples of deer at 20 microsatellite loci and a mtDNA marker. We found no evidence that either the proportion of recent hybrids, or the levels of introgression had changed over the study period. Nevertheless, in one population where the two species have been in contact since approximately 1970, 44% of individuals sampled during the study were hybrids. This suggests that hybridization between these species can proceed fairly rapidly. By analysing the number of alleles that have introgressed from polymorphic red deer into the genetically homogenous sika population, we reconstructed the haplotypes of red deer alleles introduced by backcrossing. Five separate hybridization events could account for all the recently hybridized sika-like individuals found across a large section of the Peninsula. Although we demonstrate that low rates of F1 hybridization can lead to substantial introgression, the progress of hybridization and introgression appears to be unpredictable over the short timescales.

Recruiting minorities into clinical trials: toward a participant-friendly system.

The purpose of this review is to describe the state of the art in recruiting participants for clinical trials designed to test new methods of treatment or disease prevention. The ultimate objective of this review is to provide a summary of key issues in recruiting diverse populations into clinical trials, particularly ethnic and racial minorities. An overview of general issues related to clinical trial participation is followed by a detailed discussion of specific issues that must be addressed by investigators as they recruit minority populations for clinical trial. To date, the majority of clinical trials have included a limited segment of the U.S. population: middle-class, married white males. These trials have faced many problems in their efforts to recruit participants, including barriers to physician participation, barriers to subject participation, barriers to planning and implementing effective recruitment strategies, and costs of the recruitment phase of clinical trials. Following this general introduction is a discussion of the definition of diverse populations. The first step investigators must take as they prepare to recruit study participants is to develop a relevant definition of the subject populations. A detailed review of investigators' experiences in recruiting minorities into clinical trials is presented, including barriers to minority recruitment, barriers inherent in study design, researcher bias, barriers to minority physician participation, as well as strategies for minority recruitment, modifications of study design, and cost issues. Formal evaluation of recruitment strategies has been limited. Most investigators present descriptive reports of their experience in recruiting diverse populations into clinical trials. Research into the issues presented and rigorous testing of specific strategies is needed. A series of steps that are essential to effective clinical trials recruitment of diverse populations is presented.

Tonsillectomy and Hodgkin's disease: results from companion population-based studies.

The question of whether persons with a history of tonsillectomy are at increased risk of Hodgkin's disease (HD) in adulthood was evaluated in companion population-based case-control studies conducted in the eastern Massachusetts and the Detroit metropolitan areas. These studies compared the history of tonsillectomy among incident cases with that of all their siblings by matched analysis controlling for confounding by childhood social class, family size, and birth order. Among young adults (15-39 yr) there is substantial evidence that tonsillectomy is not a risk factor and the relative risk (RR) is 1.0 (95% confidence interval, 0.72-1.4). Among middle-aged persons (40-54 yr) the RR is not significantly elevated, 1.5 (0.67-3.3), and the direction of the association differs between the sexes, consistent with the hypothesis of no association. Among older persons, the RR is significantly elevated, 3.0 (1.3-6.9), but the data are sparse. On the basis of these data, it appears unlikely that prior tonsillectomy is a causal factor in the development of HD in young and middle-aged adulthood. Whether it is a risk factor for the malignancy occurring late in life is unclear.

Risk of breast cancer to relatives of young breast cancer patients.

Breast cancer risk among sisters and mothers of a population-based series of 1,137 breast cancer patients diagnosed in Metropolitan Detroit before the age of 55 years was compared with risk to the same relatives of 1,001 age-matched, population-based controls. After adjusting for age of the relative, for age of the case or control, and for race, the odds ratio for breast cancer for women with affected sisters was 2.2; for women with affected daughters, 3.2; and for women with affected mothers and sisters, 9.9. Breast cancer in aunts had no independent influence on risk. Among white women, cumulative risk of breast cancer before the age of 50 years was approximately 1% for relatives of controls, 3% for sisters of older cases, but about 17% for women either with sisters diagnosed before the age of 40 years or with affected sisters and mothers. Sisters of the older patients had a 13% risk of breast cancer by 70 years of age, compared to 5% for sisters of controls. White women with affected mothers and sisters were at 50% risk by 65 years of age. This study identifies the criteria for women who could receive particular benefit from screening for breast cancer.

Toxic substance exposure and multiple myeloma: a case-control study.

By means of a population-based, multicenter case-control investigation, certain toxic substances were evaluated as risk factors for multiple myeloma. Interviews were completed on 698 subjects with newly diagnosed multiple myeloma, and 1,683 controls were selected from the same geographic areas as those of the cases. Respondents were asked if they had ever been "highly" exposed" to one or more of a list of toxic substances or to other substances not on the list. With the aid of a toxicologist, responses were then categorized into 20 exposure groups. Those who reported past exposure to pesticides had an estimated relative risk of 2.6 for multiple myeloma [95% confidence interval (CI) = 1.5-4.6]. Subjects exposed to a variety of compounds commonly used by painters had an estimated relative risk of 1.6 (95% CI = 1.1-2.4). An increased risk also was found for those who were exposed to sources of carbon monoxide (relative risk = 1.8, 95% CI = 1.0-3.2). Associations of borderline statistical significance were found for metals and organically high polymers (plastics and elastomers). No statistically significant associations were seen for exposure to fertilizers; dyes and inks; alkalies; acids; other caustic substances; chemical asphyxiants; aliphatic, chlorinated, or aromatic hydrocarbons; aldehydes and ketones; ethers; esters; oils; dusts; or asbestos.

Racial differences in breast cancer patients.

One thousand seventy-eight patients diagnosed with primary breast cancer were examined for racial differences in histopathologic and clinical parameters. There were no observed differences in tumor histopathologic type or tumor endocrine status between races. There were no differences with respect to time to breast tumor recurrence observed between black and white patients. However, differences were observed in factors that contributed to tumor stage at diagnosis and to tumor grade. Survival differences observed in univariant analysis of blacks vs. whites were explainable by the presence of more severe skin involvement, tumor grade, and tumor size at diagnosis in the black patients.

Cigarette smoking and pancreas cancer: a case-control study based on direct interviews.

BACKGROUND: Cigarette smoking is the most consistently reported risk factor for pancreas cancer, yet the dose-response relationship in many pancreas cancer studies is weak. Because of the poor prognosis for pancreas cancer, many case-control studies have been based largely on interviews with proxy respondents, who are known to report less reliable information on detailed smoking habits than original subjects. PURPOSE: Our purpose was to evaluate cigarette smoking as a risk factor for pancreas cancer based on data obtained only from direct interviews and to estimate the effects of quitting smoking and of switching from nonfiltered to filtered cigarettes on risk. Our objective also was to estimate the contribution of cigarette smoking toward explaining the higher pancreas cancer incidence experienced by black Americans compared with white Americans. METHODS: A population-based, case-control study of pancreas cancer was conducted during 1986-1989 in Atlanta, Ga., Detroit, Mich., and 10 counties in New Jersey. Direct interviews were successfully completed with 526 case patients and 2153 control subjects aged 30-79 years, making this the largest population-based, case-control study of pancreas cancer to date based only on direct interviews. RESULTS: Cigarette smokers had a significant, 70% increased risk of pancreas cancer compared with the risk in nonsmokers. A significant, positive trend in risk with increasing duration smoked was apparent (P < .0001), with long-term (> or = 40 years) smokers experiencing a modest 2.1-fold risk. We also observed a negative trend in risk with increasing years quit smoking. Smokers who quit for more than 10 years experienced about a 30% reduction in risk relative to current smokers; quitters of 10 years or less experienced no risk reduction. Switching from nonfiltered to filtered cigarettes did not appear to decrease risk. Compared with nonsmokers, subjects who smoked only filtered cigarettes had a 50% elevated risk and those who smoked only nonfiltered cigarettes had a 40% elevated risk. The proportion of pancreas cancer attributable to cigarette smoking was 29% in blacks and 26% in whites. CONCLUSIONS: The relationship between cigarette smoking and pancreas cancer risk is likely to be causal, despite the weakness of the dose-response data. Long-term smoking cessation clearly reduces risk, whereas switching from nonfiltered to filtered cigarettes may not be beneficial. Cigarette smoking appears to explain little of the excess pancreas cancer risk experienced by blacks. IMPLICATIONS: Elimination of cigarette smoking would eventually prevent approximately 27% of pancreas cancer, saving 6750 lives in the United States annually.

Are racial differences in squamous cell esophageal cancer explained by alcohol and tobacco use?

BACKGROUND: In the United States, incidence rates of squamous cell esophageal cancer are more than five times higher among black men than among white men. Reasons that might explain this large racial disparity are being sought. PURPOSE: We evaluated whether differential use of alcohol and tobacco can fully account for the excess of squamous cell esophageal cancer among U.S. blacks. METHODS: We conducted a population-based, case-control study with in-person interviews with 373 squamous cell esophageal cancer case patients (124 white males and 249 black males) and 1364 control subjects (750 white males and 614 black males) from three U.S. geographic areas. Histologically confirmed cases of squamous cell esophageal cancer newly diagnosed from August 1, 1986, through April 30, 1989, among white and black men aged 30-79 years were included. RESULTS: Alcohol use of more than one drink per day and/or current cigarette use of at least one pack per day accounted for 92.7% (95% confidence interval [CI] = 86.8%-98.5%) of the squamous cell esophageal cancers in blacks, versus 86.3% (95% CI = 75.5%-97.1%) in whites, and for 94% of the difference between the black and white annual incidence rates. The interaction between race and the continuous drinking/smoking variable in a logistic regression analysis was statistically significant (two-sided, P = .02). Exposure rates among controls at all levels of combined alcohol and tobacco use examined were slightly higher among blacks and accounted for a small portion of the racial differences in incidence rates. CONCLUSION: Although the vast majority of esophageal cancers in both blacks and whites in our data can be explained by use of alcohol and tobacco, it is not clear why heavy consumption of alcohol and/or tobacco is responsible for 14.9 per 100,000 per year more cases of squamous cell esophageal cancer among blacks than among whites. The differences in the odds ratios appear to account for more of the racial differences in incidence rates than do the prevalences of exposure to alcohol and tobacco alone. The reasons for this apparent racial difference in carcinogenic risk from the same level of alcohol and tobacco use are unknown, but they may include qualitative differences in alcohol consumption, differences in other environmental exposures that interact with alcohol and/or tobacco to modify risks, or differences in susceptibility to these factors.

Adenocarcinoma of the esophagus: role of obesity and diet.

BACKGROUND: In the United States, the incidence of adenocarcinoma of the esophagus, including the esophagogastric junction, has been increasing rapidly over the past two decades. Except for an association with Barrett's esophagus, little is known about the etiology of these cancers. PURPOSE: Our purpose was to investigate dietary and nutritional risk factors for adenocarcinoma of the esophagus. METHODS: A population-based, case-control interview study of 174 white men with adenocarcinoma of the esophagus and 750 control subjects living in three areas of the United States was conducted during 1986 through 1989. RESULTS: Risk was significantly elevated for subjects in the heaviest quartile compared with the lightest quartile of body mass index (odds ratio [OR] = 3.1; 95% confidence interval [CI] = 1.8-5.3). No significant associations were seen with total calories from food, number of meals eaten per day, level of fat intake, or consumption of coffee and tea. Risks were highest for those consuming the least amount of vegetables, with some evidence of a dose response for the subcategories of cruciferous vegetables (P for trend < .001) and vegetables consumed raw (P for trend = .10). A significantly elevated risk was also seen for those consuming the least amount of raw fruit (P for trend = .05). No clear associations were reported for intake of particular micronutrients overall or in supplements, but a significant protective effect was associated with increasing intake of dietary fiber (P for trend = .004). CONCLUSIONS: The findings of an increased risk with obesity and decreased risks with intake of raw fruits and vegetables and dietary fiber provide useful directions to pursue in further investigations of this malignancy. IMPLICATIONS: The finding with respect to obesity is particularly noteworthy, since it may explain at least a portion of the recent epidemic increases reported in the incidence of this tumor.

Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews.

BACKGROUND: The relationship between diet and pancreatic cancer remains unclear. In this study, we assessed the role of diet and nutrition as risk factors for pancreatic cancer, using data obtained from direct interviews only, rather than data from less reliable interviews with next of kin. We evaluated whether dietary factors could explain the higher incidence of pancreatic cancer experienced by black Americans compared with white Americans. METHODS: We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. Reliable dietary histories were obtained for 436 patients and 2003 general-population control subjects aged 30-79 years. RESULTS: Obesity was associated with a statistically significant 50%-60% increased risk of pancreatic cancer that was consistent by sex and race. Although the magnitude of risk associated with obesity was identical in blacks and whites, a higher percentage of blacks were obese than were whites (women: 38% versus 16%; men: 27% versus 22%). A statistically significant positive trend in risk was observed with increasing caloric intake, with subjects in the highest quartile of caloric intake experiencing a 70% higher risk than those in the lowest quartile. A statistically significant interaction between body mass index (weight in kg/height in m2 for men and weight in kg/height in m1.5 for women) and total caloric intake was observed that was consistent by sex and race. Subjects in the highest quartile of both body mass index and caloric intake had a statistically significant 180% higher risk than those in the lowest quartile. CONCLUSIONS: Obesity is a risk factor for pancreatic cancer and appears to contribute to the higher risk of this disease among blacks than among whites in the United States, particularly among women. Furthermore, the interaction between body mass index and caloric intake suggests the importance of energy balance in pancreatic carcinogenesis.

Marital status and cancer incidence: differences in the black and white populations.

A study of 59,070 cancers newly diagnosed during the years 1978 through 1982 among black and white males and females was conducted to assess variations in age-adjusted incidence rates across four marital categories, single, married, divorced, and widowed. Population data were obtained from the 1980 Census. Distinct patterns of cancer incidence by marital status were observed for black and white males and females. Single black males had the highest age-adjusted incidence rates for all 15 of the 15 sites analyzed among men. Similarly single black females' rates were highest for 14 of the 18 sites analyzed among women. Among white females, age-adjusted incidence rates were highest or second highest in widows for 16 of 18 sites analyzed. The variation in cancer incidence by marital status was not statistically significant for white men. In addition, there is a statistically significant concordance of cancer incidence by marital status across the four race-gender groups for three digestive tract sites. Clues to cancer etiology are suggested by this study, as well as potential directions for preventive health programs.

Motor exhaust-related occupations and bladder cancer.

The relationship between employment in occupations with potential exposure to motor exhaust and bladder cancer risk was examined based on interviews conducted with 1909 white male bladder cancer patients and 3569 population controls during the National Bladder Cancer Study, a population-based, case-control study conducted in ten areas of the United States. Our findings indicated that males usually employed as truck drivers or deliverymen have a statistically significant, 50% increase in risk of bladder cancer. Overall, a statistically significant trend in risk with increasing duration of truck driving was observed. This trend was particularly consistent for drivers first employed at least 50 years prior to diagnosis. Of these, truck drivers employed 25 years or more experienced a 120% increase in risk. Elevations in risk were also suggested for taxicab and bus drivers. These findings, coupled with experimental evidence of the mutagenicity and possible carcinogenicity of motor exhaust emission particulates, suggest a role for motor exhaust exposure in human bladder carcinogenesis.

Infectious and noninfectious exposures in the etiology of light chain myeloma: a case-control study.

Sixty-nine subjects with light chain myeloma were interviewed in a multicenter case-control study, and their responses were compared to those of 1683 controls selected from the general population of the same geographic areas. The interview was directed at the subject's history of exposure to a variety of chemical and infectious agents. Persons with a history of a medical implant had 2.2 times the risk of other persons (95% confidence interval = 0.9-5.8), a relative risk that increased with increasing time that the implant had been present. Alkali exposure that was deemed by the subject to be unusually heavy was associated with a relative risk of light chain myeloma of 7.8 (95% confidence interval = 1.7-35.3), while similarly defined exposure to carbon monoxide increased the risk by 6.1 times (95% confidence interval = 2.0-18.2). These findings differ from those obtained in our study of the more common forms of multiple myeloma and, while the differences are plausibly due only to chance given the large number of exposures investigated, they could be an indication that light chain myeloma is an etiologically distinct entity.

Alcohol and pancreatic cancer in blacks and whites in the United States.

A population-based, case-control study of pancreatic cancer based on direct interviews with 307 white and 179 black incident cases and 1164 white and 945 black population controls was conducted in three areas of the United States to determine the role alcohol drinking plays as a risk factor for pancreatic cancer and to estimate the extent to which it may explain the higher incidence of pancreatic cancer in blacks compared to whites. Our findings indicate that alcohol drinking at the levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk. Among men, blacks and white who drank at least 57 drinks/week had odds ratios (ORs) of 2.2 [95% confidence interval (CI) = 0.9-5.6] and 1.4 (95% CI = 0.6-3.2), respectively. Among women, blacks who drank 8 to < 21 drinks/week had an OR of 1.8 (95% CI = 0.8-4.0), and those who drank at least 21 drinks/week had an OR of 2.5 (95% CI = 1.02-5.9), but whites with the same levels of alcohol intake experienced no increased risk. Compared to whites, blacks had significantly higher ORs associated with heavy alcohol drinking (> or = 57 drinks/week) in men (P = 0.04) and with moderate-to-heavy drinking (> or = 8 drinks/week) in women (P = 0.03). Additional research is needed to determine whether heavy alcohol drinking is causally related to pancreatic cancer and whether the risk of alcohol-related pancreatic cancer is greater in blacks than in whites.

Use of hair dyes and risk of bladder cancer.

The relation between use of hair dyes and risk of bladder cancer was assessed using data from a case-control study of bladder cancer. Incident cases (2982) and general population controls (5782) were interviewed. The overall estimate of relative risk of bladder cancer for users of hair dyes was 1.0 (95%) confidence interval, 0.9 to 1.2) compared to nonusers. No consistent pattern of association was detected between bladder cancer risk and various indices of timing or intensity of exposure to hair dyes. Various explanations of the lack of association are discussed.

Increasing incidence of cancer of the prostate. The experience of black and white men in the Detroit metropolitan area.

BACKGROUND: Prostate cancer mortality and incidence rates have been gradually increasing for decades in the United States, with an accelerated increase in incidence noted in the past several years. This study explores in detail the occurrence of prostate cancer in southeast Michigan from 1973 through 1991. METHODS: Data from the National Cancer Institute Surveillance, Epidemiology, and End Results program are analyzed with emphasis on time trends by race, age, stage, and treatment. RESULTS: Population-based rates for prostate cancer increased by 70% between 1988 and 1991. Increases are most pronounced for early stage disease and among whites compared with blacks. Corresponding increases in treatment with radical prostatectomy are also observed. CONCLUSION: Increased incidence of prostate cancer is likely a result of widespread use of prostate-specific antigen.

Survival patterns among younger women with breast cancer: the effects of age, race, stage, and treatment.

Several hundred studies of breast cancer survival are published each year; yet few of them include women under the age of 50, and almost none of them specifically examine prognosis among women in their 20s through 40s. The few published reports that analyze survival after breast cancer among these young patients do not provide a consistent or definitive description of their survival experience. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program offers a unique opportunity to analyze breast cancer survival in depth among younger women. In this report, survival patterns of all black and white women diagnosed with breast cancer between 1983 and 1989, aged 20 and older, microscopically confirmed, and undergoing surgery, in the SEER program have been analyzed. There are 77,368 women included in this study, 92.8% of whom were white. Less than 1% (562 patients) of these breast cancer patients were between the ages of 20 and 29, 6.5% (5062 patients) were 30-39, and 15.2% (11,789 patients) were 40-49. Survival was calculated utilizing a mixture model to evaluate the cause-specific hazards of dying of breast cancer versus dying of other causes of death. We investigated the hazard of dying of breast cancer versus other causes of death by age at diagnosis, year of diagnosis, extent of disease and diagnosis, and treatment. Stage was stratified into three categories: 1) cases with no axillary lymph node involvement, 2) cases with axillary lymph node involvement, and 3) cases with distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Diversity in the association between occupation and lung cancer among black and white men.

A population-based case comparison study of incident lung cancer and occupational risk factors was conducted in the tricounty Detroit metropolitan area. Nearly 6000 lung cancer cases and a comparison group of 3600 colon cancer cases were interviewed. This report includes 3792 white and black male lung cancer cases and 1966 black and white colon cancer referents. Cigarette smoking, age at diagnosis, and lifetime work history were assessed to determine the relationship between length of employment in specific occupations and industries and lung cancer. Diverse patterns of association between work history and lung cancer were observed for black and white men. Significant associations were seen between lung cancer and increasing length of employment in the following occupations: for white men, concrete and terrazzo finishers, grinding machine operators, heat treating machine operators, miscellaneous machine operators, truck drivers, driver sales, and laborers; for black men, farm workers, automobile mechanics, painting machine operators, furnace operators, and garbage collectors; for both black and white men, farmers, slicing and cutting machine operators, and garbage collectors. Distinct patterns for black and white men also were observed for length of employment by industry. This study clearly demonstrates the need to include black men in studies of occupational cancer etiology and to evaluate black and white men separately. It also indicates the necessity for cigarette smoking history to accurately assess workplace cancer risks. We propose guidelines for incorporating the use of biomarkers into further studies of occupational cancer epidemiology.

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.