Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk

The risk of colorectal cancer associated with smoking is unclear and may be influenced by genetic variation in enzymes that metabolize cigarette carcinogens. The authors examined the colorectal cancer risk associated with smoking and 26 variants in carcinogen metabolism genes in 1,174 colorectal cancer cases and 1,293 population-based controls recruited in Canada by the Ontario Familial Colorectal Cancer Registry from 1997 to 2001. Adjusted odds ratios were calculated by multivariable logistic regression. Smoking for >27 years was associated with a statistically significant increased colorectal cancer risk (adjusted odds ratio (AOR) = 1.25, 95% confidence interval (CI): 1.02, 1.53) in all subjects. Colorectal cancer risk associated with smoking was higher in males for smoking status, duration, and intensity. The CYP1A1-3801-CC (AOR = 0.47, 95% CI: 0.23, 0.94) and CYP2C9-430-CT (AOR = 0.82, 95% CI: 0.68, 0.99) genotypes were associated with decreased risk, and the GSTM1-K173N-CG (AOR = 1.99, 95% CI: 1.21, 3.25) genotype was associated with an increased risk of colorectal cancer. Statistical interactions between smoking and genetic variants were assessed by comparing logistic regression models with and without a multiplicative interaction term. Significant interactions were observed between smoking status and SULT1A1-638 (P = 0.02), NAT2-857 (P = 0.01), and CYP1B1-4390 (P = 0.04) variants and between smoking duration and NAT1-1088 (P = 0.02), SULT1A1-638 (P = 0.04), and NAT1-acetylator (P = 0.03) status. These findings support the hypothesis that prolonged cigarette smoking is associated with increased risk of colorectal cancer and that this risk may be modified by variation in carcinogen metabolism genes.     

Health risk behaviors: examining social inequalities in bladder and colorectal cancers

PURPOSE: The objective of this study is to estimate the proportion of the relationship between low socioeconomic status (SES) and the incidence of these cancer types accounted for by health risk behaviors. METHODS: A study population of 569 bladder, 592 colon, and 558 rectal cancer cases and 1549 controls was used to investigate health risk behaviors and SES effects. Odds ratios and 95 % confidence intervals (CIs) estimated by multivariate logistic regression approximated relative risks. The explanatory role of health risk behaviors was assessed by the change in the risk estimate on SES following their omission from the model. RESULTS: For each cancer site, individual education remained a predictor of risk after controlling for health risk behaviors. Adjustments for health risk behaviors (smoking) shifted the age- and sex-adjusted relative risk (RR) associated with bladder cancer from 2.24 to 1.74 (29.5%). No health risk behaviors (smoking, diet, obesity) resulted in substantial change in the low education risk estimates for colon cancer (RR = 2.88) or rectal cancer (RR = 2.42). CONCLUSIONS: Given the strength of SES relationships persisting after adjustment for health risk behaviors, this study suggests that our knowledge of SES pathways and risk factors for bladder, colon, and rectal cancers is incomplete.     

Cigarette smoking, tumor recurrence, and survival from bladder cancer

Results are presented from an investigation into the effects of cigarette smoking on tumor recurrence and survival in a group of 302 patients with bladder cancer. A regression analysis using Cox's proportional hazards model was done to evaluate the effect of cigarette smoking status, stage of disease at diagnosis, histology, race, sex, and the patient's age at diagnosis on length of survival. Results showed that younger patients, those with less extensive disease, and those with transitional cell tumors showed the best survival. Cigarette smoking was unrelated to survival. The effects of cigarette smoking on tumor recurrence were examined in patients with localized disease. Smoking status was not associated with either recurrence-free survival or the number of tumor recurrences. These findings suggest that cigarette smoking is not an important prognostic factor for patients with bladder cancer.     

Cigarette smoking and breast cancer risk

Luo et al. have had the advantage of assessing active and passive smoking effects on breast cancer in 40 clinical centers in the USA involving 79,990 women aged 50-79 years, who were enrolled in the Women's Health Initiative Observational Study from 1993 to 1998. This is the possibly the largest cohort that has demonstrated the hazards of cigarette smoking and its impact on carcinoma of the breast in women.     

Cigarette smoking and risk of adult leukemia

A case-control study investigated the relation between cigarette smoking and histologic subtypes of adult leukemia in Missouri in 1984-1990. Among males, elevated risks associated with ever smoking were observed for acute nonlymphocytic leukemia (odds ratio (OR) = 1.5; 95% confidence interval (CI) 1.1-2.0) and acute myelocytic leukemia (OR = 1.5; 95% CI 1.1-2.1). Females also showed an increased risk of acute nonlymphocytic leukemia associated with ever smoking (OR = 1.4; 95% CI 1.0-1.9), with an increasing trend in risk by level of smoking (p less than 0.01). Attributable risk estimates of the proportion of acute nonlymphocytic leukemia caused by smoking were 33 percent in males and 29 percent in females. Elevations in risk were not apparent for chronic forms of leukemia. The findings support the hypothesis that some types of leukemia may be etiologically related to cigarette smoking.     

Tea consumption and risk of bladder and kidney cancers in a population-based case-control study

Recent epidemiologic studies have suggested that tea may be protective against cancers of the urinary tract. The authors examined the association between usual adult tea consumption and risk of bladder and kidney cancers in a population-based case-control study that included 1,452 bladder cancer cases, 406 kidney cancer cases, and 2,434 controls. For bladder cancer, the age- and sex-adjusted odds ratios (OR) (95% confidence intervals (CI)) referent to nonusers of tea were 0.9 (0.7, 1.1) for <1.0 cup/day, 1.0 (0.8, 1.2) for 1.0-2.6 cups/day, and 0.9 (0.7, 1.1) for >2.6 cups/day (cutpoints for users based on the tertile distribution among controls). When more extreme cutpoints were used, persons who consumed >5 cups/day (>90th percentile) had a suggestive decreased risk (OR = 0.7; 95% CI 0.5, 1.0), but there was no evidence of a dose-response relation. In analyses stratified by median total beverage intake (2.6 liters/day), there was an inverse association with tea use among persons who consumed less than the median (OR = 0.5; 95% CI 0.3, 0.8) but no association for persons who consumed at or above the median. In contrast, for kidney cancer, there was no association with tea use. Adjustment for site-specific risk factors did not alter these results. This study offers only minimal support for an inverse association between tea consumption and bladder or kidney cancer risk.     

Tobacco smoking, smoking cessation, and cumulative risk of upper aerodigestive tract cancers

Upper aerodigestive tract cancers are strongly related to smoking, and their incidence is substantially lower in former smokers than in continuing smokers. To estimate the effect of smoking cessation on the cumulative incidence of these cancers by age 75 years (in the absence of competing causes of death), the authors combined odds ratios for males from a network of Italian hospital-based case-control studies (1984-2000) with 1993-1997 incidence data for Italian men. The studies included 961 cases with oral/pharyngeal cancer, 618 cases with esophageal cancer, and 613 cases with laryngeal cancer, plus 3,781 controls. For all upper aerodigestive tract cancers, the cumulative risks by 75 years of age were 6.3% for men who continued to smoke any type of tobacco, 3.1% and 1.2% for men who stopped smoking at around 50 and 30 years of age, respectively, and 0.8% among lifelong nonsmokers. Corresponding figures were 3.3%, 1.4%, 0.5%, and 0.2% for oral/pharyngeal cancer; 1.0%, 0.5%, 0.4%, and 0.2% for esophageal cancer; and 2.1%, 1.1%, 0.2%, and 0.2% for laryngeal cancer. In this Italian population, men who stopped smoking before age 50 years avoided more than half of the excess risk of upper aerodigestive tract cancer as men who did not, and men who stopped smoking before age 30 years avoided more than 90% of the risk.     

Cigarette smoking and risk of breast carcinoma in situ

BACKGROUND: Although the associations with cigarette smoking have been explored extensively for invasive breast cancer, the relation to in situ cancer has not previously been examined in depth. METHODS: We analyzed data from a population-based case-control study of women living in Wisconsin, Massachusetts, and New Hampshire. Eligible cases of incident breast carcinoma in situ were reported to statewide registries in 1997-2001 (n = 1878); similarly aged controls (n = 8041) were randomly selected from population lists. Smoking history and other risk factor information were collected through structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated from logistic regression models adjusting for potential confounders. RESULTS: In multivariate models, the OR for breast carcinoma in situ among current smokers was 0.8, compared with never-smokers (95% CI = 0.7-1.0). Risk estimates increased towards the null with greater time since smoking cessation. Odds ratios were also less than 1.0 among women who initiated smoking in adolescence (OR = 0.8) or after a full-term birth (OR = 0.7), relative to women who never smoked. The reduced odds ratios associated with current smoking were strongest among women with annual screening mammograms (OR = 0.7; 95% CI = 0.6-0.9). Odds ratios were not less than 1.0 among current smokers without a recent screening mammogram (1.3; 0.9-2.0). CONCLUSIONS: Our findings suggest an inverse association between current smoking and risk of breast carcinoma in situ among women undergoing breast cancer screening.     

Cigarette smoking and the risk of breast cancer

The authors examined the relation between cigarette smoking and breast cancer in the Centers for Disease Control Cancer and Steroid Hormone Study, a multicenter, population-based case-control study. The study compared 4,720 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4,682 women randomly selected from the same geographic areas. Women who reported ever smoking cigarettes had a risk of breast cancer of 1.2 (95 percent confidence interval 1.1-1.3) compared with never smokers. There was no consistent dose-response pattern with any measure of smoking (pack-years of smoking, average number of cigarettes per day, or total years smoked) and little difference in risk between current and former smokers. There was some variation in risk by age, with slightly higher risk estimates for younger women than for older women. Although current smokers had an earlier natural menopause than did never smokers, the authors found no evidence of a protective effect of cigarette smoking on breast cancer risk. These findings suggest that the risk of breast cancer in women who smoke is the same as, or perhaps slightly higher than, women who have never smoked.     

Cigarette smoking and the risk of cervical neoplasia

The relationship between cigarette smoking and risk of cervical neoplasia was evaluated in a case-control study of 183 women with cervical intraepithelial neoplasia compared with 183 age-matched outpatient controls, and of 230 cases of invasive cervical cancer compared with 230 controls in hospital for acute conditions unrelated to any of the identified or suspected risk factors for cervical cancer. Current cigarette smoking was associated with an elevated risk of cervical intraepithelial neoplasia (relative risk = 1.76, 95 per cent confidence interval = 1.14-2.27) and of invasive cancer (relative risk = 1.69, 95 per cent confidence interval = 1.08-2.65). This association was only partially accounted for by a large number of identified potential confounding factors, including indicators of socioeconomic status and sexual habits. The risk increased with the number of cigarettes smoked and was apparently greater for women who started smoking at younger ages. The relative risk of intraepithelial neoplasia was elevated within 20 years after the start of smoking and showed little tendency to increase with increasing duration. On the other hand, the risk of invasive cervical cancer was apparently unaffected by smoking less than 20 years and increased steadily thereafter, reaching a point estimate of 3.63 after 40 years or more. If one assumes that intraepithelial neoplasia is an early stage of cervical cancer, this pattern of risk is consistent with the predictions from the multistage theory of carcinogenesis, if the effect of smoking is on one of the earlier stages. No obvious distorting factors, apart from the play of chance, is likely to produce such a risk pattern.     

Cigarette smoking and the risk of natural menopause

We reviewed published studies on the association of age at natural menopause and cigarette smoking. All demonstrated an earlier median or mean age of menopause among smokers; for current smokers vs noncurrent smokers the difference ranged from 0.8 to 1.7 years. For studies that presented suitable data, we computed prevalence odds ratios of menopause for current smokers vs never-smokers, current smokers vs noncurrent smokers, and former smokers vs never-smokers. The Mantel-Haenzel summary odds ratios and 95% confidence intervals for these contrasts were: 1.9 (1.7-2.2), 1.7 (1.5-1.9), and 1.3 (1.0-1.7). Studies that presented data on amount of cigarettes smoked per day demonstrated "dose-response" trends when analyzed using the Mantel-Haenszel extension. The consistency of results across studies, the persistence of the effect when age and other covariates were considered, and the dose-response relation all support the hypothesis that smoking increases the risk of early menopause.     

Cigarette smoking and the risk of diabetes in women.

OBJECTIVES. Noninsulin-dependent diabetes mellitus, a major risk factor for cardiovascular disease, is prevalent in more than 12 million Americans. A voluminous amount of data demonstrates that cigarette smoking is an important cause of cancer and coronary heart disease. However, the association between cigarette smoking and the risk of diabetes is virtually unexplored, especially in women. METHODS. We examined the association between smoking and the incidence of noninsulin-dependent diabetes mellitus among 114,247 female nurses who were free of diabetes, cardiovascular disease, and cancer in 1976. We collected exposure information and disease status prospectively for 12 years from biennially self-administered questionnaires. RESULTS. Current smokers had an increased risk of diabetes, and we observed a significant dose-response trend for higher risk among heavier smokers. During 1,277,589 person-years of follow-up, 2333 women were clinically diagnosed with diabetes. The relative risk of diabetes, adjusted for obesity and other risk factors, was 1.42 among women who smoked 25 or more cigarettes per day compared with nonsmokers. CONCLUSIONS. These data suggest that cigarette smoking may be an independent, modifiable risk factor for noninsulin-dependent diabetes mellitus.     

Cigarette smoking and the risk of epithelial ovarian cancer

Cigarette smoking may affect each of the currently proposed mechanisms of ovarian carcinogenesis. Whether cigarette smoking has any effect on the development of ovarian cancer has not been adequately evaluated. To study this issue, the authors examined data from the Cancer and Steroid Hormone Study, a multicenter, case-control study of gynecologic cancers conducted between December 1, 1980, and December 31, 1982, in eight geographic areas of the United States. This analysis utilized data on 494 women with newly diagnosed epithelial ovarian cancer and 4,238 population-based control women 20-54 years of age. There was no association of epithelial ovarian cancer with dose of cigarette smoking, age smoking started, time since smoking started, or time since smoking last occurred. Simultaneous adjustment for age, parity, history of oral contraceptive use, and other potentially confounding factors did not alter these results.     

Cigarette smoking and the risk of anogenital cancer.

The association between cigarette smoking and cervical cancer has been demonstrated in numerous prior studies. As part of population-based case-control studies of cancers of the vulva, vagina, cervix, anus, and penis in relation to infection with human papillomavirus, conducted in western Washington State and the province of British Columbia from the mid 1980s until the present time, the authors have collected detailed information on smoking history. The proportion of subjects who were current smokers of cigarettes ranged from slightly over 40% among incident cases of vaginal and cervical cancer to 60% among cases of vulvar and anal cancer. In contrast, only about 25% of controls were current smokers. The adjusted odds ratios (OR) associated with current smoking were substantially elevated (OR = 1.9-14.6) for all cancer sites except cancer of the vagina (OR = 1.3). The risks tended to increase in proportion to the number of cigarettes smoked. For most cancer sites, the odds ratios associated with former smoking were substantially less than those associated with current smoking and diminished with increasing time since cessation of smoking. The authors' data and those of other investigators suggest that cigarette smoking plays a role in the etiology of anogenital cancers and that smoking has a late-stage or promotional effect.     

吸烟与结核病发病风险及戒烟后复吸的相关因素研究

目的 探讨吸烟与结核病发病风险和戒烟后复吸的危险因素.方法 对613例肺结核病例和1226例健康对照采用结构化问卷调查表进行调查.吸烟与结核病患病风险的关联采用Logistic回归分析,并用OR及其95％CI表示.戒烟者中复吸的危险因素采用Cox回归模型进行分析,并用风险比(hazard ratio,HR)及其95％ CI表示.Kaplan-Meier生存曲线用于比较不同治疗史和不同教育背景的病人戒烟后复吸风险的差异,并采用Log-rank法进行检验.结果 病例组中有吸烟史者(54.6％)高于对照组(45.1％),调整OR=1.93(95％ CI:1.51～2.48).尽管54.9％的结核病人在获知其结核病诊断后停止吸烟,但仍有18.4％的戒烟者在随访期内复吸,复吸高发于戒烟后6～9个月(6％)和12 ～15个月(11％).与受教育程度高和有过结核病治疗史的患者比较,受教育程度低和初治患者戒烟后复吸的风险增加,调整HR分别为3.48 (95％CI:1.28～9.47)和4.30(95％ CI:1.01～18.30).结论 吸烟是中国人群结核病预防和控制工作的一个重要因素,应当将控烟干预指导纳入现行的直接督导短程化疗(directly observed therapy shortcourse,DOTS)策略中去.     

Cigarette smoking and increased risk of mucinous epithelial ovarian cancer

Several studies have reported that cigarette smoking is associated with an increased risk of mucinous ovarian cancer, but other studies have failed to find such a relation. Using data from the Case-Control Surveillance Study, begun in four US cities in 1976, the authors conducted a case-control study (1976-2001) to examine the association between cigarette smoking and the risk of ovarian cancer of different cell types. Among 709 incident cases of epithelial ovarian cancer, 402 were serous, 74 were mucinous, 106 were endometrioid, and 127 were of other cell types. For mucinous ovarian cancer, the odds ratios were 1.5 (95% confidence interval (CI): 0.7, 3.4) among women who smoked less than one pack of cigarettes per day, 1.4 (95% CI: 0.6, 3.5) among women who smoked one pack per day, and 2.9 (95% CI: 1.2, 7.5) among women who smoked more than one pack per day, relative to never smokers. The odds ratios were 2.5 (95% CI: 1.1, 5.4) for ex-smokers and 1.4 (95% CI: 0.7, 2.9) for current smokers. While women with up to 15 pack-years of smoking had an almost 2.5 times' increased risk of mucinous ovarian cancer, such an increased risk was not found among those with more than 15 pack-years of smoking. There was no association between cigarette smoking and epithelial ovarian cancer of other cell types. Despite inconsistencies in the data, these results strengthen the evidence that cigarette smoking may play a role in the development of mucinous ovarian cancer but not ovarian cancer of other cell types.     

Triple primary cancers involving kidney,urinary bladder,and liver in a dye worker

A case of triple primary cancers (renal cell carcinoma of the kidney, transitional cell carcinoma of the bladder, and hepatocellular carcinoma of the liver) was reported at autopsy. A 53-year-old man, who had a history of exposure to benzidine, underwent nephrectomy for a left renal cell carcinoma and 10 years later, transurethral resection of bladder tumor (TUR-Bt) for a transitional cell carcinoma of the bladder. At the age of 65, he was diagnosed as having multiple hepatic tumors. Histological examination of biopsy specimens showed these lesions to be undifferentiated carcinomas. Immunohistological examination of both biopsy and autopsy specimens revealed that multiple hepatic tumors were hepatocellular carcinomas, not metastatic tumors from kidney or urinary bladder: tumor cells of hepatic tumors were positive for α-fetoprotein, although renal cell carcinomas and transitional cell carcinomas of urinary bladder were positive for Ber-EP4 and keratin, respectively. These findings suggest not only that immunohistological examination is helpful for the diagnosis of multiple primary cancers but also that benzidine may be hepatocarcinogenic in addition to those cancers that are known to be associated with benzidine exposure, i.e., renal cell carcinomas and transitional cell carcinomas in urinary bladder. Am. J. Ind. Med. 31:44–49 © 1997 Wiley-Liss, Inc.     

Fluid intake and risk of bladder and other cancers

There are appreciable differences in total fluid intake at the individual and population level, and substantial difficulties in obtaining valid measures of fluid intake. Epidemiological studies have examined the association between fluid intake and different types of cancer. For bladder cancer, fluid consumption has been associated with a moderate increase of risk in some studies, including a multicentric case-control study from the United States, based on about 3000 cases, with a decrease in others, including the Health Professional Follow-up study, or with no material association. The evidence, therefore, is far from consistent. Sources and components of fluids were also different across different types studies. From a biological point of view, a decreased fluid intake could result in a greater concentration of carcinogens in the urine or in a prolonged time of contact with the bladder mucosa because of less frequent micturition. Carcinogenic or anticarcinogenic components of various beverages excreted in the urine may also play a role in the process. It has been suggested that fluid consumption has a favorable effect on colorectal cancer risk. Fluid intake may reduce colon cancer risk by decreasing bowel transit time and reducing mucosal contact with carcinogens. Low fluid intake may also compromise cellular concentration, affect enzyme activity in metabolic regulation, and inhibit carcinogen removal. However, epidemiological data are inadequate for evaluation. Data are sparse and inconsistent for other neoplasms, including breast cancer. The fluid constituent of foods, confounding, interactions and possible influences of specific types of beverages should be investigated further. In conclusion therefore the association between total fluid intake and cancer risk remains still open to debate.