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Learn more about Amazon Prime. A day later another body, partially eaten by a gator, is found floating in the old forgotten underwater Chinese Graveyard. Guy LeBlanc is not your usual homicide detective. With his long raven hair, casual dress and deep blue eyes he is a man not easily forgotten and as the body count begins to rise, LeBlanc must now come to grips with not only a string of grisly murders, but the intensifying psychic ability he has inherited from his biological father, Harbin LeFleur, a Creole Voodoo Priest.
As former Special Forces officer who specialized in black ops and now unsure of whom he can trust he calls in part of his former unit to find and overturn the organized conspiracy headquartered in a secluded swamp in southeast Louisiana. Read more Read less. Prime Book Box for Kids. Guy LeBlanc Book 2 Paperback: Print edition purchase must be sold by Amazon.
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Related Video Shorts 0 Upload your video. Try the Kindle edition and experience these great reading features: Return to Book Page. Lieutenant Guy LeBlanc is not your usual homicide detective. With his long, almost raven hair, casual dress and deep blue eyes he is a man not easily forgotten. Now faced with a serial killer preying on women Lieutenant Guy LeBlanc is not your usual homicide detective.
The brutality increases with each murder and suddenly it becomes clear that the killer is an expert in Black Voodoo.
Suspicion begins to fall not only on LeBlanc, but those who surround him. Was it for her protection or is she in more danger Kindle Edition , pages. To see what your friends thought of this book, please sign up. To ask other readers questions about The Mojo Murders , please sign up. Lists with This Book. In another study from Philip Morris, Patskan and colleagues compared the mutagenic activity of Marlboro full flavor, Marlboro Lights, and Marlboro Ultra Lights, finding that mutagenic activity was higher per mg of total particulate matter for Marlboro Ultra Lights, but this was for only some Salmonella strains used in the mutagenicity testing and for only some runs.
Thus, the evidence supports a modest increase in the mutagenicity of tobacco tar as the level of machine-measured tar falls; this effect may result from increased ventilation. These data should be interpreted with caution for several reasons. Mutagenicity is generally used as only a screening test, is often poorly associated with carcinogenicity in humans, and has not been quantitatively associated with differences in human risk. In addition, most of the studies described previously compared smoke generated under standardized machine-testing protocols. In actual use, smokers change their patterns of smoking, compensating for the design changes that result in lower yields of machine-measured tar and nicotine.
This compensatory smoking behavior makes comparisons of cigarettes with very different machine-tested yields difficult to interpret relative to carcinogenicity in humans when the smoke for the different cigarettes is generated using a single, standardized, machine-smoking protocol. Existing evidence about changes in the patterns of smoking cigarettes with low yields of tar and high ventilation supports a shift in the deposition of smoke in the lung toward the alveolar region; this shift likely contributes to the observed increase in adenocarcinoma of the lung.
Research has not clarified whether the magnitude of this shift in lung deposition, by itself, is great enough to explain the dramatic increase in adenocarcinoma observed in the United States. The mutagenicity of tobacco tar from cigarettes with lower yields of machine-measured tar is trending upward.
However, the trend is modest in size, and difficulties in extrapolating results from mutagenicity testing to risk for humans make it difficult to know whether these changes contribute to increasing the risk of lung cancer. The design and composition of cigarettes have changed substantively since the first major wave of evidence linking smoking to lung cancer in the s.
Although the details of these changes are only partially understood, changes in design—notably the addition of ventilated filters—have clearly changed the pattern of smoking, including more intense puffing. In addition, changes in the composition of cigarettes have resulted in incompletely characterized alterations in the chemical composition of cigarette smoke. Documented changes include increases in tobacco-specific nitrosamines and decreases in PAHs in the smoke of U. Substantial differences between U. The United States has somewhat preceded most other developed countries in the adoption of filtered and low-yield, machine-tested cigarettes, but U.
These changes raise a question of whether rates of lung cancer have been altered by the changes in the design and composition of cigarettes—changes that were accompanied by an initial belief that lower yields of machine-tested tar might signal a lower risk for lung cancer. In fact, the risk of lung cancer in the United States may have increased as a result of such changes. Comparison of results of CPS-I and CPS-II—two large epidemiologic studies conducted 20 years apart by ACS—demonstrated an increased risk of death from lung cancer from smoking across the year interval between the studies.
For female smokers, the results from the contemporary cohorts show that lung cancer risk continued to rise through — Modeling of risks of lung cancer from smoking behaviors suggests that risk estimates based on the smoking experience in the s underestimated the current incidence of lung cancer.
In addition, the incidence of adenocarcinoma of the lung and the proportion of lung cancer that is adenocarcinoma has increased dramatically during the past several decades. This shift from squamous cell carcinoma to adenocarcinoma is confined to smokers, because neither the overall risk of lung cancer nor the risk of adenocarcinoma has changed over time among never smokers. The rate of squamous cell carcinoma of the lung has declined in the United States since the s and is well-predicted by declines in smoking behaviors, but the rate of adenocarcinoma continued to rise for an additional 10—15 years before either leveling off or beginning to decline.
Birth-cohort-specific analyses of trends in overall mortality from lung cancer and the incidence of type-specific lung cancer suggest that increases in diagnostic accuracy, differences by tumor type in the time course of excess risk reduction with cessation, and underestimation of the effect of intensity and duration of smoking in the studies that defined risk in the s do not explain the observed trends.
In contrast, a change in the risk of the cigarettes smoked over time does explain the increase in risk. A shift in the demographic composition of smokers toward those groups with less income and education may contribute to the increased risk of lung cancer among smokers, but this shift does not likely explain the increase in adenocarcinoma or the difference in the rates of incidence of squamous cell carcinoma and adenocarcinoma.
Most countries have experienced increases in the proportion of all lung cancer that is adenocarcinoma, but substantial differences are found in the extent of this increase when comparing the United States, where blended cigarettes are used, with Australia and Canada, where unblended cigarettes are used. Adenocarcinoma in the United States has increased more steeply, represents a much higher fraction of lung cancer, and has higher absolute incidence rates than those of Australia or Canada. Compared with unblended cigarettes, U. Exposure to tobacco-specific nitrosamines is also much higher among U.
Levels of a metabolite of NNK, a tobacco-specific nitrosamine, are an independent risk predictor for the occurrence of lung cancer after controlling for the intensity and duration of smoking. Compensatory changes in the patterns of puffing and inhaling smoke by smokers switching to cigarettes with low yields of toxicants may increase the deposition of smoke particles in the alveolar region of the lung.
This is supported by modeling of particle deposition in the lung that suggests this effect likely increases the deposition of particles in the alveolar region. Increased alveolar deposition and increasing tobacco-specific nitrosamine levels over time may have combined to increase the risk for adenocarcinoma. The evidence presented has multiple implications. Above all, if the risk of lung cancer has increased with changes in the design and composition of cigarettes, then the potential exists to reverse that increase in risk through changes in design and composition.
Even a modest reduction in the large burden of mortality from lung cancer would result in saving substantial numbers of lives over time. The evidence reviewed suggests that differences in the design and composition of cigarettes may contribute to differences in smoking-related risks of lung cancer in different populations and different geographic locations. Data also suggest that epidemiologic studies treating all cigarettes as having identical risks, or using single biomarkers of exposure to quantify actual exposure to the multiple carcinogens in cigarette smoke, should be undertaken with some caution.
The number of cigarettes smoked per day, measures of cotinine in biologic samples, and other measures of total smoke exposure will remain useful for estimating total smoke exposure and population risk. However, the potential for differences in products to yield differences in risk suggests that a broader array of biomarkers of exposure should be used to examine whether differences in the toxicity and composition of a given total exposure to smoke may also play an important role in determining differences in risks.
The changing risk for lung cancer associated with cigarettes over time also has implications for the surveillance of tobacco products. Monitoring tobacco products needs to go beyond tracking the most obvious changes, such as the addition of a filter, to assess the characteristics of the tobacco in the cigarette, how the product is manufactured, how it is likely to be smoked, the design of the cigarette, and its performance under a variety of smoking patterns.
The absence of such information for past and current tobacco products limits the ability to more fully study the effects of changes in the design and composition of cigarettes on risks of disease. The availability of such information could help in the assessment of potential differences in risks going forward. Finally, the rise in the risk of adenocarcinoma of the lung from smoking was unanticipated. This experience, like that of cigarettes with purportedly low yields of toxicants, indicates that changes to cigarettes should undergo careful, evidence-based assessments as such changes are being considered.
In many parts of the world, liver cancer remains a leading cause of cancer mortality. Primary liver cancer, the great majority of which is hepatocellular carcinoma HCC , generally presents at an advanced stage with limited treatment options and a poor prognosis.
Although worldwide liver cancer is the sixth most common cancer in terms of incidence, it represents the third most common cause of cancer-related death Ferlay et al. The incidence of liver cancer varies geographically worldwide, with rates generally consistent with the regional prevalence of the primary viral etiologic factors Nordenstedt et al.
Rates of HCC appear to have stabilized or started to decline in several Asian countries, where widespread vaccination against HBV and reduction of HBV cofactors have occurred during the past few decades Yuen et al. Historically, the United States has had a low incidence of liver cancer and low death rates for the disease.
However, obesity, diabetes, and associated nonalcoholic fatty liver disease, and the substantial burden of chronic HBV infection among foreign-born Asians may also be potential contributors to the increasing incidence of HCC Larsson and Wolk ; Starley et al. In addition to viral hepatitis, cirrhosis from consumption of alcohol represents an important cause of HCC worldwide London and McGlynn HCC is more common among men than women, which likely reflects gender differences in exposure to viral hepatitis and rates of progression of that disease, differences in smoking and in consumption of alcohol, and perhaps hormonal differences.
For example, people who drink alcohol are more likely to be smokers than people who do not drink alcohol Dawson In addition, most HCV infections worldwide are acquired by injecting drugs, and the prevalence of smoking is very high among injection drug users Marshall et al. In regions of the world with a high incidence of HCC, HBV infection is generally acquired perinatally or during early childhood. However, in other regions, HBV may be more commonly acquired through parenteral or sexual transmission; these behaviors may also be associated with smoking. Hence, the potential confounders must be examined carefully when assessing the association between smoking and HCC.
However, considerable epidemiologic evidence, including data from studies in which measures have been taken to address potential confounding, indicates that smokers are at an increased risk for liver cancer IARC The Surgeon General's report on smoking cessation USDHHS noted an association between smoking and HCC that persisted after controlling for potentially confounding lifestyle factors, including consumption of alcohol. The report also noted that HBV infections may modify the effects of smoking on the risk of liver cancer.
The Surgeon General's report on the health consequences of smoking USDHHS noted a consistent association between smoking and HCC after controlling for potentially confounding factors, but it called for further consideration of the history of viral hepatitis and consumption of alcohol.
Overall, the report concluded that although the data were suggestive of an association between smoking and liver cancer, further evidence was required to classify smoking as a cause of liver cancer. Circulating carcinogens from tobacco smoke are metabolized in the liver, exposing the liver to many absorbed carcinogens.
Experimental studies have identified several constituents of tobacco smoke e. Limited human data on smoke-related carcinogens have suggested increased levels of 4-aminobiphenyl and PAH adducts in HCC tissues compared with normal liver tissues Wang et al. Therefore, long-term exposure to carcinogens in smoke may lead to cellular damage in the liver and contribute to the development of cancer.
Cigarette smoking may also contribute to liver carcinogenesis through the development of liver fibrosis Dev et al. Similar to their effects on other fibrogenic conditions e. Smoking has also been recognized as a risk factor for primary biliary cirrhosis, which itself can progress to HCC Zein et al. Although their results have been inconsistent, several epidemiologic studies have demonstrated that smoking substantially increases the risk for progression from chronic liver disease to HCC Tsukuma et al.
Since the report of the Surgeon General, 90 additional studies have been published or identified that report on the association between smoking and liver cancer. IARC concluded that there was sufficient evidence of a causal association between cigarette smoking and liver cancer. Subsequently, Lee and colleagues published a meta-analysis that was based on the studies considered in the IARC report.
The epidemiologic data came from a wide range of studies in both low- and high-incidence countries Tables 6. For many studies, the outcome was defined as HCC and was based on clinical, radiographic, laboratory alpha-fetoprotein levels , or pathologic criteria. A minority of studies relied on linkage to cancer or mortality registries, often using primary liver cancer as the outcome defined by the coding of cancer diagnoses from the International Classification of Disease for Oncology or causes of death from the International Classification of Diseases. Some studies were unable to distinguish between HCC and intrahepatic cholangiocarcinoma; however, none of these studies were from geographic regions where intrahepatic cholangiocarcinoma would likely represent a substantial portion of primary liver cancers.
Studies that did not explicitly differentiate between primary and secondary liver cancer and therefore may have included cancers with a different primary site that had metastasized to the liver were excluded from the analysis. This review focused on evaluations of the separate effects observed in current smokers, ever smokers, and former smokers in comparisons with never smokers or nonsmokers; studies with a reference group other than never smokers or nonsmokers were excluded e. The quantitative analyses excluded all studies that compared liver cancer cases with controls who had chronic viral hepatitis, cirrhosis, or other chronic liver disease.
Overall, studies—including 59 case-control Table 6. These studies, taken together, offered substantial heterogeneity in design, study population, assessment of smoking exposure, and the reporting of risk estimates. Many studies, however, were limited by having few HCC cases and reported nonsignificant increases in risk associated with various measures of smoking. Furthermore, many studies did not adequately control for potential confounding by major causal factors such as consumption of alcohol or HBV or HCV infection.
In an analysis combining data from 31 studies 12 case-control and 19 cohort that reported sufficient information to estimate risk for HCC in current smokers compared with nonsmokers Figure 6. When 11 studies 6 case-control and 5 cohort that controlled for confounding by the primary etiologic factors e. The findings of the IARC review and the current review are similar, except that the present review includes a greater number of studies 31 vs. Both the present review and the IARC analysis defined current smoking as reported at entry into the cohort or at the time of diagnosis of liver cancer.
Estimated risk for liver cancer in current smokers compared with nonsmokers. Weights are from random effects analysis. Estimated risk for hepatocellular carcinoma in current smokers compared with nonsmokers among studies that controlled for confounding by primary etiological factors viral hepatitis, consumption of alcohol.
Among 26 studies 18 case-control and 8 cohort with evaluable comparisons between ever smokers and never smokers Figure 6. In the 4 studies that adjusted for exposure to the primary etiologic agents Figure 6. Estimated risk for hepatocellular carcinoma in ever smokers compared with never smokers. Estimated risk for hepatocellular carcinoma in ever smokers compared with never smokers among studies that controlled for confounding by primary etiological factors viral hepatitis, consumption of alcohol. Among 33 case-control studies that evaluated dose-response relationships between smoking e.
Many studies that evaluated dose response did not formally test for trends; however, a substantial proportion of these studies were not adequately powered to address such relationships. In their meta-analysis, Lee and colleagues summarized data from 7 studies with evaluable estimates and reported a significant dose-response trend showing increased risk for liver cancer with higher number of cigarettes smoked.
However, this effect was notably less apparent among case-control studies that used hospital-based instead of population-based control groups. Because of concern for residual confounding of smoking effects by coinfection with viral hepatitis, the association between smoking and HCC was evaluated in the present review among persons who did not have evidence for chronic viral hepatitis.
In an analysis combining data from 13 studies 9 case-control and 4 cohort that estimated risk among persons who were negative for markers of chronic HBV or HCV infection Figure 6. Finally, when the analysis was restricted to the 3 studies that included only persons negative for both HBsAg and anti-HCV and also adjusted for consumption of alcohol Kuper et al. Estimated risk for hepatocellular carcinoma among persons without evidence for chronic viral hepatitis infection for current or ever smokers compared with never smokers. The present review did not identify any studies that directly evaluated the effects of interventions aimed at smoking cessation on subsequent risk for liver cancer.
Among 23 studies with the requisite data available from the publication 11 case-control and 12 cohort Figure 6. Estimated risk for hepatocellular carcinoma in former smokers compared with never smokers. Despite substantial geographic variation in the incidence of HCC and the distribution of etiologic factors, smoking was consistently related to increased risk for HCC in all geographic regions, although the magnitude of the association was not as strong in studies conducted in European countries.
Among 35 studies conducted in Asian countries Table 6. In countries in sub-Saharan Africa, the present data analysis was limited to case-control studies that evaluated ever smoking. Each study suggested an association between smoking and HCC, but none of them were statistically significant—likely because of the limited number of cases. Overall, the RR from the three studies with data available Kew et al. Veterans of the armed services were substantially overrepresented in these studies. The overall RR estimate in an analysis that combined current and ever smoking was 1.
Among the 14 studies reviewed from countries in Europe, 11 were case-control studies, largely from southern Europe, and 3 were cohort studies. Substantial heterogeneity was observed in these studies. In a series of case-control studies from Greece, smoking was consistently associated with HCC, but the associations were more pronounced and statistically significant among HBV-negative persons Trichopoulos et al. Elsewhere, 4 case-control studies from Italy reported null findings Filippazzo et al.
In 2 cohort studies from Sweden, the risk estimate in 1 study among females was less than 1. But, the other study observed increased rates of mortality from liver cancer among a cohort of men and a significant dose-response association with increased smoking Carstensen et al. In a Europe-wide cohort study, Trichopoulos and colleagues rigorously characterized the smoking behavior, alcohol consumption, diet, and viral hepatitis status of a half-million people.
Finally, in a quantitative analysis for the present review from 5 evaluable studies in Europe, the RR for HCC among current or ever smokers La Vecchia et al. Similar to the experience in Greece, several studies from other regions suggested a higher risk of liver cancer with smoking among HBV-negative persons than among those who were HBV positive Lam et al.
The risk of colon cancer was elevated among former smokers but not current smokers, while there were no significant findings for rectal cancer. DeVita and Rosenberg Unfortunately, researchers in the past did not have access to information about the nature and extent of these and other changes in cigarettes because they were handled as trade secrets and, therefore, not disclosed by the industry. Mary Beth rated it liked it Feb 20, However, by creating and sustaining addiction, it leads to the prolonged exposure to tobacco smoke that increases cancer risk for smokers.
Some other studies, however, failed to find any difference in this risk by HBV status Kew et al. And yet, according to eight studies published in or later, smokers with chronic HBV or HCV infection have a substantially higher risk for HCC than those who do not have chronic hepatitis infection Mori et al.
Formal evaluations of interactions between smoking and HBV or HCV infections have been reported infrequently from these studies. Although the present review focuses on HCC, which represents a substantial majority of primary liver cancer, a meta-analysis by Wenbin and colleagues reported on the association between smoking with gallbladder cancer.
Overall, a substantial body of evidence documents the association between smoking and primary liver cancer. The role of the liver as a primary site for metabolism of several recognized carcinogens provides strong biologic plausibility for a causal association between smoking and HCC. In epidemiologic studies from various geographic regions and with different designs, findings demonstrate a consistent but nonuniform association between smoking and primary liver cancer.
In the expanded meta-analysis included in this report, studies were identified that reported data on the risk of liver cancer from smoking. Although confounding by consumption of alcohol and HBV or HCV infection status may bias the findings of some studies, controlling for these risk factors does not fully account for the effects seen. Furthermore, the effect of ever smoking on risk of liver cancer was strengthened in the studies that addressed primary confounding factors. Risk for liver cancer was significantly increased in former smokers compared with never smokers, although risk for former smokers was attenuated relative to risk for current smokers.
While heterogeneity was observed in studies that evaluated dose-response associations, meta-analysis of a limited number of studies with data that could be combined suggested that increased smoking intensity increases the risk for liver cancer. The finding of increased risk for liver cancer from smoking was generally consistent regardless of geography or study design.
Greater heterogeneity was observed in studies from Europe than elsewhere. Several hospital-based case-control studies from southern Europe reported null or nonsignificant associations and the overall relationship between smoking and liver cancer was thus notably smaller in Europe. Modification of the effect of smoking on risk for liver cancer by viral hepatitis has been suggested, although formal statistical evaluation remains limited.
Stronger associations between smoking and HCC among persons who are negative for HBV infection have been observed in studies conducted on selected populations in Europe and China. In contrast, most studies from diverse regions—such as Asia, Egypt, Europe, and the United States—have found greater risks for liver cancer from smoking among persons with chronic HBV or HCV infections.
The burden of liver cancer is increasing in many regions of the world, notably due to HCV-related cases of HCC occurring in more developed countries. Among such persons, smoking also increases risk and consequently incidence and death rates related to liver cancer may continue to grow substantially in the more developed countries with rising HCC. In high-burden regions of the world where vaccination against HBV or reductions in exposure to aflatoxin are being achieved, rates of liver cancer are expected to decline.
However, if smoking increases in these low- and middle-income countries, then the potential for reducing liver cancer from these preventive interventions will not be fully realized. Colorectal cancer—that is, cancer of the colon or rectum—is the third most common type of cancer in the United States and also ranks third as a cause of cancer deaths among men and women in the United States Siegel et al.
For , the ACS projected , new cases of cancer of the colon and 40, new cases of cancer of the rectum as well as 51, deaths from the two cancers combined Siegel et al. In the mids, the lifetime probability of developing colorectal cancer was estimated to be 5. Worldwide, incidence and death rates for colorectal cancer vary more than fold among countries.
Studies show that among immigrants moving from low- to high-incidence countries, rates increase within one generation to the approximate rates of the new country, suggesting a strong role for environmental agents Thomas and Karagas Risk also varies substantially even within countries.
For example, in a study by Wei and colleagues of a middle-aged cohort of U. An increased risk of colorectal cancer has been linked to a variety of risk factors, including physical inactivity Wolin et al. Risk for colorectal cancer also increases for persons with a family history of colorectal cancer or polyps Fuchs et al. Conversely, several factors are consistently associated with a reduced risk of colorectal cancer, including the use of aspirin and other nonsteroidal anti-inflammatory drugs NSAIDs.
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Aspirin use of 10—20 years is associated with a decreased risk of colorectal cancer mortality Flossmann and Rothwell , and short-term or current use of hormone replacement therapy HRT reduces risk in women Rossouw et al. In addition, higher levels of vitamin D may protect against adenomatous polyps and incidence, recurrence, and death from colorectal cancer Ng et al. Calcium supplementation reduces the risk of recurrent polyps Baron et al. Initially, there was concern that this observed association reflected uncontrolled confounding factors, such as lifestyle characteristics, as well as differences in risk between colon and rectal cancer, which are often combined in epidemiologic studies.
Subsequent studies suggested a stronger relationship between smoking and rectal cancer than between smoking and colon cancer Terry et al. This difference was confirmed in two meta-analyses that were limited to prospective cohort studies Liang et al. In the latter systematic review, Botteri and colleagues searched the literature through May and evaluated data from six studies that compared the association of smoking and colon cancer separately from smoking and rectal cancer mortality. The RRs of ever smokers and current smokers were significantly higher for rectal cancer mortality than for colon cancer rectal cancer: Until the Surgeon General's report on women and smoking USDHHS , the reports of the Surgeon General on smoking had not considered the relationship of smoking with cancers of the colon and rectum.
The Surgeon General's report, after reviewing extensive evidence, concluded that the evidence is suggestive but not sufficient to infer a causal relationship between smoking and colorectal adenomatous polyps and colorectal cancer. Most cancers of the colon and rectum are adenocarcinomas. These tumors typically develop from clonal expansions of mutated cells through a series of histopathologic stages—from single crypt lesions to benign tumors adenomatous polyps to metastatic carcinomas—that take place over a span of 20—40 years Fearon and Vogelstein On the basis of the observation that mutations of the APC gene on chromosome 5q are found as frequently in small adenomatous polyps as in cancers, the loss of normal APC function is considered an early and possibly initiating event in colorectal tumorigenesis Powell et al.
Products of the APC gene influence cell proliferation, adhesion, migration, and apoptosis. Activating mutations in codons 12 and 13 of the RAS oncogene are important in the progression of adenomas but are not directly involved in malignant transformations in the bowel Bos ; Ohnishi et al.
Slattery and colleagues related smoking to microsatellite instability a genetic marker in colon tumors, and Curtin and colleagues a showed microsatellite instability in rectal tumors that were diagnosed in current smokers. Clonal expansion of colorectal tumors containing mutant p53 genes gains a selective survival advantage for these tumors and they become increasingly invasive and metastatic.
Cigarette smoke contains many carcinogens, PAHs, heterocyclic aromatic amines, and N -nitrosamines Hoffmann and Hoffmann that can reach the large bowel via the circulatory system Giovannucci and Martinez One study documented that DNA adducts to metabolites of B[ a ]P, a potent PAH, in colonic mucosa occur more frequently and at higher concentrations in smokers than in nonsmokers Alexandrov et al. Moreover, DNA adduction levels in the colonic epithelium were found in one study to be higher in tumor tissue from persons with colorectal cancer than from control subjects Pfohl-Leszkowicz et al.
Other genes known to be important in colorectal cancer include mismatch repair genes associated with the hereditary familial syndrome, nonpolyposis colorectal cancer, or sporadic cases of colorectal cancer Liu et al. One study associated cigarette smoking with a mismatch repair deficiency in colorectal cancer, as reflected by a sixfold increase in the risk of microsatellite instability in tumors in current smokers compared with nonsmokers Yang et al.
Elsewhere, in a large case-control study of incident colon cancer, Curtin and colleagues b evaluated base excision repair and observed a twofold increase in the risk of tumor mutations in current and former smokers. More generally, research continues to provide insight into pathways by which smoking could increase risk for colorectal cancer Campbell et al. To date, the association between cigarette smoking and colorectal cancer has not been found to be modified by polymorphisms of genes that are important in the detoxification of carcinogens found in tobacco smoke, including GSTM1, GSTT1, and NAT2 Gertig et al.
However, when researchers examined only adenomas that were 1 centimeter cm or larger, current smokers with the GSTM1 null genotype were at a higher risk than those without the null genotype Lin et al. Furthermore, some evidence suggests an increased risk of colorectal cancer and advanced polyps in smokers with GST1 null genotype Ates et al. Overall, a meta-analysis of 12 studies that evaluated polymorphisms in GSTM1 did not show any significant interaction with smoking and risk Raimondi et al.
Combined data from 7 of the 12 studies indicated that smokers with mEH3 low- or medium-metabolizer genotypes had a slightly lower risk of colorectal adenoma than smokers with mEH3 high-metabolizer genotypes. None of the other common genetic polymorphisms involved in metabolizing tobacco carcinogens modified the risk of colorectal adenoma or cancer.
Animal models of the carcinogenicity of tobacco in the colon and rectum have been limited to date and have not included studies in which the route of exposure was inhalation. In inbred male Syrian hamsters, adenocarcinomas of the colon have been produced by intrarectal instillation of B[ a ]P Wang et al. Finally, in vitro studies have shown that both rat and human colonic epithelium in cell cultures can enzymatically activate B[ a ]P Autrup et al. The published studies on cigarette smoking and colorectal adenomatous polyps and cancer cited in this section were identified by updating through December the search of the MEDLINE database from through July that was used in the Surgeon General's report.
In addition, this more recent search included examination of the Web of Science and Embase, also through December Since the s, the association between cigarette smoking and colorectal adenomas and cancer has been evaluated in many prospective and case-control studies; the present review extends work summarized in the Surgeon General's report and focuses on published studies that excluded cigar and pipe smokers, identified lifetime nonsmokers, and distinguished current smokers from former smokers. If multiple reports resulted from the same prospective cohort, then the results from the longest follow-up are used unless otherwise stated.
Botteri and colleagues b used rigorous search and data extraction techniques to synthesize the evidence for an association between smoking and the risk of adenomatous polyps. Among articles published from —, they evaluated in detail; these studies were conducted in countries around the world.
An evaluation for publication bias by Botteri and colleagues b showed no indication of such bias for the reporting of results about current smokers, but there was evidence for reports related to former and ever smokers. Forest plot of relative risk for colorectal adenoma for current smokers versus never smokers.
Adapted from Botteri et al.