Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.     

Pneumocephalus and respiratory depression after accidental dural puncture during epidural analgesia--a case report

BACKGROUND: Adenomatous colonic polyps are accepted as premalignant lesions. There is controversy regarding the significance of the hyperplastic polyp. The aim of this study was to determine the incidence of further polyps in patients with only hyperplastic polyps on a first colonoscopy in comparison with patients without polyps and with adenomatous polyps. METHODS: Ninety patients had only hyperplastic polyps (group I). These patients were paired according to age and sex with subjects having no polyps (group II) and with patients having adenomas (group III). RESULTS: Fifty-six patients in group I had at least one follow-up examination. New polyps were found in 46.4% in group I versus 15.5% in group II (p < 0.001) and 50% in group III (NS). In group I, 30.7% of new polyps were hyperplastic and 69.3% were adenomas. In fact, 32.2% of group I patients developed further adenomas (mean 1.5 +/- 0.8 adenomas). These adenomas occurred 1 to 4 years after the first polypectomy (mean 2.4 +/- 0.8 years). Most of these adenomas were small and tubular, but 16.6% were villous or had severe dysplasia. CONCLUSION: Patients with hyperplastic polyps were 2.4 times more likely to have further adenomas than were those without polyps.     

A case-control study of dietary intake and other lifestyle risk factors for hyperplastic polyps

BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little is known about its etiology. The aim of this study was to assess the relationship between diet and other lifestyle factors and the presence of colorectal hyperplastic polyps. METHODS: Information on diet and other known or suspected risk factors for colorectal cancer or adenoma was collected among 81 subjects with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with individuals in the lower category, those in the upper category of body mass index had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97). Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81 for > 20 pack-years vs. never), whereas an inverse association was seen for use of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12-0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share common lifestyle risk factors with colorectal adenomas and carcinomas.     

Cigarette smoking and the colorectal adenoma-carcinoma sequence: a hypothesis to explain the paradox

As recognized precursor lesions to colorectal cancer, colorectal adenomatous polyps have been studied to enhance knowledge of colorectal cancer etiology. Although most of the known risk factors for colorectal cancer are also associated with the occurrence of colorectal adenomas, cigarette smoking has had a strong, consistent relationship with colorectal adenomas but is generally not associated with colorectal cancer. The explanation for this paradox is unknown. With data collected in 1986-1988 during a large case-control study based on colonoscopy results in New York City, New York, the authors investigated the possibility that the paradox may arise because subjects with colorectal adenomas were included in the control group of cancer case-control studies. The authors found a statistically significant increased risk between heavy cigarette smoking (smokers with > or = 40 pack-years of smoking) and risk of adenoma (odds ratio (OR) = 1.61, 95% confidence interval (CI) 1.06-2.44). They saw no increased colorectal cancer risk from heavy cigarette smoking (OR = 1.02, 95% CI 0.52-1.99) using a "manufactured" control group to simulate a typical unscreened, population-based control group. When the authors compared these colorectal cancer cases with an adenoma-free control group examined by colonoscopy in a polytomous model with several case groups (newly diagnosed adenomas, carcinoma in situ, intramucosal carcinoma, and colorectal cancer), they found that the risk for 20-39 pack-years of smoking was elevated, although not statistically significant, and was similar for all four case groups. The risk for the highest smoking category (> or = 40 pack-years) was more strongly elevated in all four case groups, although it was statistically significant for only the newly diagnosed adenoma and the carcinoma in situ cases (adenomas, OR = 1.59, 95% CI 1.05-2.42; carcinoma in situ, OR = 2.05, 95% CI 1.01-4.15; intramucosal carcinoma, OR = 1.30, 95% CI 0.61-2.77; and colorectal cancer, OR = 1.30, 95% CI 0.64-2.65). While the authors' study is weakened by the lack of statistical significance concerning risk for colorectal cancer, these data offer some support for the hypothesis that the association between cigarette smoking and risk of colorectal cancer may have been masked by inclusion in the control group of subjects with adenomas. They also suggest that the major effect of smoking on the colorectal adenoma-carcinoma sequence occurs in the earlier stages of the formation of adenoma and the development of carcinoma in situ.     

A prospective evaluation of the safety and efficacy of methohexital in the emergency department

OBJECTIVE: Knowledge of a possible correlation between distal polyps found at screening sigmoidoscopy and proximal colonic lesions is important for deciding whether to perform total colonoscopy or not. PATIENTS: A prospective analysis of 2439 consecutive patients with colorectal polyps. Of these, 304 were asymptomatic subjects who underwent complete colonoscopy for screening and were found to have adenomatous or hyperplastic polyps in the distal colorectum. RESULTS: Ten (15%) out of 65 patients with distal hyperplastic polyps only and 86 (36%) out of 239 with distal adenomatous polyps were found to have adenomatous polyps in the proximal colon as well (P < 0.001). The frequency of synchronous proximal adenomas in patients with small (< or = 5 mm) or large distal adenomas (> 5 mm) was comparable (37% and 35%, respectively). However, patients with small distal adenomas had significantly smaller proximal adenomas (P = 0.004) containing less villous component (P = 0.017) than those with large distal adenomas. Neither the patient's age nor the presence of multiple distal adenomas increased the prevalence of proximal adenomas. CONCLUSION: Hyperplastic polyps found on rectosigmoidoscopy do not indicate a need for a complete colorectal examination, as 15% of patients with distal hyperplastic polyps will have proximal adenomatous polyps, a figure that is comparable with that of asymptomatic patients having no distal polyps, either hyperplastic or adenomatous. When only small distal adenomas are found at screening sigmoidoscopy in asymptomatic persons the decision to do a total colonoscopy should be based on individual considerations, as in such cases only small polyps are to be expected in the proximal colon.     

Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies

To examine the effects of smoking and N-acetylation genetics on breast cancer risk, we analyzed data from an ongoing, population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 498 cases and 473 controls, with approximately equal numbers of African-American and white women, and women under the age of 50 and age 50 years or older. Among premenopausal women, there was no association between current smoking [odds ratio (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95% CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also no association with current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1) for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and 0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1) nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased breast cancer risk. There was little evidence for modification of smoking effects according to genotype, except among postmenopausal women. Among postmenopausal women, ORs for smoking within the past 3 years were greater for women with the NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI, 0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast cancer should investigate the effects of environmental tobacco smoke, diet, and other exposures.     

Long term follow-up of patients with acute myelogenous leukemia who received the daunorubicin, vincristine, and cytosine arabinoside regimen

Some previous studies have suggested that the fast phenotype of the N-acetyltransferase NAT2 may confer susceptibility to colorectal cancer because of greater activation of dietary heterocyclic amines, particularly in individuals who also consume well-done red meat, but other studies have not supported this. We describe a large case-control study examining the interaction between dietary, smoking and drinking habits, and acetylation genotype in relation to susceptibility to colorectal cancer. One-hundred-and-seventy-four incident cases and 174 matched controls were recruited. Genotyping for polymorphisms in NAT2 was performed using a method that detects >95% of slow alleles and data on personal habits were collected using a standardized questionnaire. We found no difference in the frequency of the fast acetylator genotype between cases and controls [odds ratio = 0.95 (95% CI 0.61-1.49)], and analysis by sex, age and site also revealed no difference in acetylator genotype. There was, however, considerable heterogeneity in dietary risk factors between fast and slow acetylators. Analysis by acetylator type shows that recent smoking was more frequent in slow acetylator cases than matched controls [OR = 2.31 (1.16-4.6)] and that heavy alcohol consumption was also more frequent in the slow acetylator cases than controls [OR = 2.5 (1.02-7.29)]. In contrast, frequent fried meat intake was seen more frequently in fast acetylator cases than matched controls [OR = 6.0 (1.34-55)]. The odds ratio for the combination of fast acetylator status and frequent fried meat consumption in cases was 6.04 (1.6-26). Our study suggests that there may be different risk factors for colorectal cancer in slow and fast acetylators, and reveals a new observation that slow acetylators may be at risk of colon cancer from smoking. In our community, the overall effect of acetylator status on colorectal cancer risk is neutral.     

Benign symmetrical lipomatosis: Madelung''s disease

The relationship between smoking and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 151 males with incident, histologically confirmed invasive cancer of the bladder, and controls were 157 males admitted to hospital for acute, non-neoplastic, non-urinary tract, non-smoking-related conditions. With reference to never smokers, ex-smokers had a multivariate odds ratio (OR) of 4.4 [95% confidence interval (CI) 1.7-11.7] and current smokers of 6.6 (95% CI 3.1-13.9). The ORs were 5.4 for < 20 and 7.6 for > or = 20 cigarettes per day. After adjustment for cigarette smoking, the ORs were 0.8 for waterpipe and 0.4 for hashish smokers. The risk was significantly related to duration of smoking (OR of 16.5 for > 40 years), and inversely related to age at starting (OR of 8.8 for starting < 20 years), and inversely related to time since quitting smoking. Compared with never smokers who did not report a clinical history of schistosomiasis, the OR was 9.4 for smokers with a history of schistosomiasis, and 10.7 for smokers ever employed in high-risk occupations compared with non-smokers not reporting such a history. Thus, our results, while not giving indications of an increased bladder cancer risk with habits other than cigarette smoking, found a remarkably strong association with various measures of cigarette smoking that could explain 75% of bladder cancer cases among males from Alexandria. The prevalence of smoking was very low among women, and consequently tobacco was not a relevant risk factor for female bladder cancer.     

Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps

Altered mucin glycosylation and the de novo appearance of gastric mucin antigens have been described in colonic adenomas. The purpose of our study was to determine if expression of the gastric mucin genes MUC5AC and MUC6 occurs in colorectal adenomas and whether this correlates with histopathologic criteria of malignant potential. Immunohistochemical staining using antibodies against MUC5AC and MUC6 tandem repeat synthetic peptides was performed on specimens of normal colon mucosa (n = 26), hyperplastic polyps (n = 9) and adenomatous polyps (n = 111). Mucin mRNA levels were determined using RNase protection assays using riboprobes corresponding to unique non-repetitive sequences. MUC5AC and MUC6 staining were rarely detected and of low intensity in normal colon and hyperplastic polyps. The number of immunoreactive polyps and intensity of MUC5AC and MUC6 staining were greatest in larger adenomas of moderate villous histology and dysplasia. MUC5AC and MUC6 staining tended to decrease in highly villous polyps with severe dysplasia. Increased MUC5AC mRNA levels were found in 26/45 of adenomas tested compared with 0/9 normal colon specimens. MUC6 mRNA levels were found in 20/45 of adenomas compared with 1/9 normal colon specimens. MUC5AC and MUC6 mRNA were present more frequently and at higher levels in polyps with intermediate stages of size, villous histology and dysplasia. We conclude that aberrant expression of MUC5AC and MUC6 mucin genes is likely responsible for an expanded repertoire of mucin antigen expression in colorectal neoplasia.     

Clinical evaluation of fundic gland polyps and hyperplastic polyps

We performed a retrospective review of 477 cases of fundic gland polyps compared with 562 cases of hyperplastic polyps, which were detected endoscopically during the past 8 years between January, 1989 and December, 1996. All lesions were histologically confirmed by endoscopic biopsy or the examination of polypectomy specimens. Fundic gland polyps were more prevalent in middle aged-female, and were not associated with gastric adenomas and gastric cancers. These results suggested that the background mucosa of patients with fundic gland polyp was different from that of patients with hyperplastic polyp. Fundic gland polyps in 55 patients were followed up. No change was observed in the polyps of the about half subjects, the polyps of 12 cases (21.8%) decreased in size and number or resolved completely. Cases decreased in size and number or resolved completely were much more in fundic gland polyps than hyperplastic polyps. There were no malignant transformation of fundic gland polyps. We claimed that fundic gland polyps were benign and distinct from hyperplastic polyps which had a possibility of malignant transformation.     

Surgical site infections

OBJECTIVE: Investigate risk factors for colon polyp using multivariate analyses. DESIGN: In a group responding to a 1992 mail survey, we assessed the association between physician-diagnosed colon polyp and possible risk factors reported primarily 10 years earlier. SETTING: Survey respondents within the Cancer Prevention Study II. PARTICIPANTS: Respondents, 72,868 men and 81,356 women, who reported no polyp diagnosis when questioned in 1982 at ages 40 to 64 years. MEASUREMENTS AND MAIN RESULTS: The characteristics of 7,504 men (10.3%) and 5,111 women (6.3%) reporting a first colon polyp were compared with those of participants who did not report a polyp. After adjustments for age, family history of colorectal cancer, and other potential risk factors, polyp occurrence was associated with 1982 histories of smoking, former smoking, alcohol use of at least two drinks per day (odds ratios [ORs] from 1.5 to 1.1; all p < .005), and a body mass index > or = 28 kg/m2 (men's OR 1.06; 95% confidence interval [CI] 1.00, 1.13; women's OR 1.08; 95% CI 0.99, 1.17). Polyps were also associated with a diagnosis of gallbladder disease or gallstone at any time and with gallbladder surgery up to 1982 (OR from 2.7 to 1.3; all p < .001). Polyp occurrence was inversely associated with 1982 histories of high exercise level (men's OR 0.83; 95% CI 0.76, 0.91; women's OR 0.90; 95% CI 0.78, 1.03), frequent aspirin use in women (OR 0.85; 95% CI 0.77, 0.95), and high parity in women (OR 0.84; 95% CI 0.75, 0.94). Among participants lacking a clinically normal gallbladder, the polyp risks associated with smoking and high body mass index were reduced (p < .04 for interactions). CONCLUSIONS: Despite the limitations and potential biases in these self-reported data, the risk factors described here may be useful for identifying persons at modestly increased risk of having a colon polyp. The effect-modifying role of gallbladder status deserves further investigation.     

Lack of association between the polyadenylation polymorphism in the NAT1 (acetyltransferase 1) gene and colorectal adenomas

Smoking and a high intake of red meat are risk factors for colorectal tumors. These effects could be due to aromatic amine carcinogens. Individual susceptibility to aromatic amines has been related to acetylation phenotype, which plays a role in the bioactivation of arylamines. Polymorphisms in both N-acetyltransferase genes, NAT1 and NAT2, have been associated with an increased risk of colorectal tumors. We studied the NAT1*10 fast acetylator allele (1088 T-->A mutation) and distal adenomas in a sigmoidoscopy-based case-control study (441 cases, 484 controls). We found neither an increased adenoma prevalence in subjects homozygous or heterozygous for the NAT1*10 fast acetylator allele (odds ratio 1.04; 95% confidence interval 0.79-1.36), nor a gene-gene interaction between NA1 and NAT2 (P(interaction) = 0.59). Further NAT1 alleles must be considered for more conclusive results regarding the relevance of NAT1 activity to colorectal tumorigenesis.     

Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice

Mutations in the human adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed Apc gene knockout mice that contained a truncation mutation at codon 716 (Apc(delta716)). The heterozygous mice developed numerous intestinal polyps. All microadenomas dissected from nascent polyps had already lost the wild-type allele, indicating the loss of heterozygosity (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). We also demonstrated that cyclooxygenase 2 is induced in the polyps at an early stage and plays a key role in polyp development (M. Oshima et al., Cell 87: 803-809, 1996). We have analyzed the process of polyp development in these mice both at morphological and molecular levels. A small intestinal microadenoma is initiated as an outpocketing pouch in a single crypt and develops into the inner (lacteal) side of a neighboring villus forming a double-layer nascent polyp. The microadenoma then enlarges and gets folded inside the villus. When it fills the intravillous space, it expands downward and extends into adjoining villi, rather than rupturing into the intestinal lumen. During this course of development, the basement membrane remains intact, and the labeling index of the microadenoma cells is similar to that of the normal crypt epithelium. As in the crypt cells, neither transforming growth factor beta1 nor its receptor type II is expressed in the microadenoma cells. No hot spot mutations in the K-ras gene are found in the microadenoma tissue during these early stages of polyp development. Essentially, the same results have been obtained for the colonic polyps as well. These results suggest that early adenomas in the Apc(delta716) polyps are very similar to the normal proliferating cells of the crypt except for the lack of directed migration along the crypt-villus axis.     

Aromatic hydrocarbon receptor polymorphism: development of new methods to correlate genotype with phenotype

BACKGROUND: Non-steroidal anti-inflammatory drugs can reduce the risk of colorectal cancer. Reportedly, mRNA expression of cyclooxygenase-2 (COX-2) is elevated in human colorectal cancers compared with accompanying normal mucosa. The present study was undertaken to establish a simple analytical procedure to quantify COX-2 expression levels and to characterize COX-2 expression levels in human colorectal cancers, adenomas and hyperplastic polyps. METHODS: The combination of PCR using common primers designed in the highly conserved regions and fluorescence-based single-strand conformation polymorphism (F-SSCP) analysis of the products is used for quantitative determination of the proportions of COX-2 mRNA in human colorectal cancers, adenomas, hyperplastic polyps and accompanying normal mucosa. RESULTS: The present F-SSCP analysis was a simple and powerful method for quantitative determination of the proportions of COX-2 mRNA. The proportion of COX-2 mRNA was higher in cancer tissues than in accompanying normal mucosa in 46 of the 50 cancers. There was no significant correlation between the increase of the COX-2 proportion and tumor location or stages. The enhanced COX-2 expression was also observed in colorectal adenomas. On the other hand, the proportion of COX-2 mRNA in hyperplastic polyps was not significantly different from that in normal mucosa. CONCLUSIONS: The proportion of COX-2 to COX-1 expression was elevated in most human colorectal cancers and adenomas, but not in hyperplastic polyps. Therefore, the increased proportion of COX-2 expression might be an early event in the carcinogenesis of colorectal cancer.     

A normal initial colonoscopy after age 50 does not predict a polyp-free status for life

OBJECTIVES: The prevalence of colon polyps increases with age in the general population. It is unknown whether a lack of adenomatous polyps determined at one time point after the age of 50 is predictive of a subsequent low risk of polyp development. METHODS: Twenty-nine patients between ages 50 and 70 who had no prior history of polyps and had a normal colonoscopy at least 5 yr previously were recruited for follow-up colonoscopy to evaluate the incidence of neoplastic disease in this presumably low-risk group. RESULTS: The incidence of adenomatous polyps after a mean of 5.74 yr was 41.4% (95% confidence interval: 23.5-61.1%). A total of 20 adenomatous polyps were found in 12 patients. Seven polyps were 5 mm or more in size. CONCLUSIONS: We conclude that in patients with no history of colonic neoplasia who are 50 yr old, or older, the finding of a normal colonoscopy does not predict diminished risk of neoplasia.     

Colorectal lesions predisposing to cancer

Precursors of colorectal carcinoma are adenomatous polyps, sporadic or arising in familial adenomatous polyposis and Lynch syndrome and chronic inflammatory lesions related to ulcerative colitis and Crohn's disease. The adenoma-carcinoma sequence is well established and early detection and removal of colorectal adenomas is thought to prevent colorectal cancer in high risk asymptomatic persons, i.e. subjects over 45 years, with personal or familial history of adenomas and colorectal cancers. The precancerous potential of adenomatous polyps varies according to tissue type, with increased risk with the extent of the villous component, high grade of dysplasia, large size greater than 1 cm and multiple adenomas. The development of de novo colorectal cancer from normal mucosa with flat adenomas has been recently emphasized. The risk of colonic cancer in patients with ulcerative colitis and Crohn's disease is controversed.     

Relation of cigarette smoking to non-Hodgkin's lymphoma among middle-aged men

Because of previous inconsistencies in the observed relation of cigarette smoking to non-Hodgkin's lymphoma, this association was investigated in the Selected Cancers Study, a population-based case-control study of 1,193 non-Hodgkin's lymphoma cases and 1,903 controls, conducted between 1984 and 1988. Study subjects were men, and the median age of non-Hodgkin's lymphoma cases was 50 years (range, 32-60 years). As compared with the risk among men who had never smoked cigarettes, the risk among ever smokers was not increased (odds ratio (OR) = 1.05, p approximately 0.50), but the risk was significantly elevated among men who reported smoking > or = 2 1/2 packs per day and among men who had smoked for 30-39 years (OR = 1.45 in each group, p < 0.05). The estimated odds ratio among the 350 heavy smokers (> or = 50 pack-years) was 1.41 (95% confidence interval 1.08-1.85) after controlling for educational achievement, various occupational and medical exposures, and other potential confounders. The observed associations, however, tended to vary by age, with the odds ratio among heavy smokers decreasing from 2.8 among 32- to 44-year-olds to 1.1 among men over 55 years of age. These age-related differences, which may account for some of the inconsistencies seen in previous studies of cigarette smoking and non-Hodgkin's lymphoma, should be considered in future investigations.     

Citation for the Distinguished Physician Award of the Endocrine Society to Dr. John P. Bilezikian

OBJECTIVE: To elucidate the molecular mechanism of smoking cessation and its relationship to body weight gain, the effects of smoking on the serum levels of leptin were studied in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The serum levels of leptin after an overnight fast in 37 adult male Japanese patients with type 2 diabetes (17 smokers and 20 nonsmokers) were assayed using radioimmunoassay. In addition, the serum leptin levels in four nondiabetic smokers were measured before and 2 weeks after quitting smoking. RESULTS: Smokers and nonsmokers did not differ in age, BMI, or levels of blood glucose and fasting insulin but did differ in HDL cholesterol levels (1.07 +/- 0.18 vs. 1.32 +/- 0.24 mmol/l for smokers and nonsmokers, respectively, P = 0.002). The mean serum leptin level of smokers did not differ from that of nonsmokers (3.8 +/- 1.9 vs. 3.8 +/- 1.6 ng/ml). The leptin level correlated with the fasting insulin level and BMI (r = 0.55 and 0.56, P < 0.001 and 0.001, respectively). The leptin levels in four heavy smokers showed no change after the subjects quit smoking (3.3 +/- 1.0 vs. 3.8 +/- 1.8 ng/ml, before and after quitting, respectively). CONCLUSIONS: Because smoking did not affect the leptin levels, the effects of quitting smoking on the fuel metabolism appear to be due to some other factors.     

Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt

The relationship between history of schistosomiasis and bladder cancer risk was investigated using data from a case-control study conducted between January 1994 and July 1996 in Alexandria, Egypt. Cases were 190 subjects with incident, histologically confirmed invasive cancer of the bladder, and controls were 187 subjects admitted to hospital for acute, non-neoplastic, non-urinary tract conditions. Eighty-six cases (45%) vs 69 controls (37%) reported a history of urinary schistosomiasis. The corresponding multivariate odds ratio (OR) of bladder cancer -- after allowance for age, sex, education, smoking, other urinary infections and high-risk occupations -- was 1.72 (95% confidence interval (CI) 1.0-2.9). The ORs were 0.22 (95% CI 0.1-0.4) for intestinal schistosomiasis and 0.32 (95% CI 0.1-1.9) for schistosomiasis of other types. The OR for urinary schistosomiasis was higher in subjects who were younger at first diagnosis (OR of 3.3 for <15 years) and in those with a long time since first diagnosis (OR of 3.0 for > or = 35 years). The ORs were 15.8 for male ever-smokers with a history of urinary schistosomiasis, compared with never-smokers without such a history, and 3.2 for men ever-infected with urinary Schistosoma haematobium and ever-employed in high-risk occupations, compared with those never-infected and with no high-risk occupational history. This study confirms that clinical history of urinary schistosomiasis is significantly, but modestly, associated with increased bladder cancer risk, explaining some 16% of bladder cancer cases in this Egyptian population.     

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.