Tobacco Smoking and Gastrointestinal Cancer Risk

Abstract

Background

Smoking tobacco is the most preventable cause of gastrointestinal (GI) cancer disease in Germany. The more and the longer you smoke, the higher your risk of GI cancer. About 28% of 18–64 year-old Germans are current smokers; in addition, 11% of the population is regularly exposed to secondhand tobacco smoke.

Summary

Tobacco use is causally associated with esophageal, gastric, pancreatic, biliary, hepatocellular, colorectal, and anal cancers. Combining smoking with alcohol use, excess body weight, diabetes, or chronic infections synergistically enhances GI cancer risk. Smoking cessation effectively reduces tobacco-associated GI cancer risk.

Key Messages

Smokers should be encouraged to stop smoking tobacco and join programs of risk-adaptive cancer screening.

Introduction

Cancer is the major cause of death among adults aged 35–70 years in high-income countries. Among 35–70 year olds of high-income countries, deaths from cancer outnumber those from cardiovascular disease more than twice [1]. In many industrialized countries, lifetime cancer risk of the average population has risen to 35% and higher.

Smoking is the most important and preventable cause of cancer deaths. Tobacco acts on multiple stages of carcinogenesis; it delivers carcinogens directly to tissues, causes irritation and inflammation, and interferes with the body's natural protective barriers and defense mechanisms. Up to 30% of cancer deaths both in the USA and in Europe are due to tobacco use [2, 3, 4]. Tobacco smoking is causally associated with esophageal, gastric, pancreatic, biliary, hepatocellular, colorectal, and anal cancers. Depending on sex and site 8–52% of those malignancies are caused by smoking [3, 4]. In Korea, 51% of esophageal cancer deaths, 19% of liver, 21% of stomach, and 15% of pancreas cancer deaths are attributable to tobacco smoking [5].

A low-risk lifestyle can reduce overall gastrointestinal (GI) cancer risk by about 50% [6]. Stopping the use of tobacco yields remarkable health benefits. In particular smoking cessation reduces tobacco-associated excess GI cancer risk [7].

About 28% of 18–64 year-old Germans are current smokers. In addition, 11% of the population IS regularly exposed to secondhand tobacco smoke. Another 23–27% of German adults are former smokers [8, 9, 10]. Thus, about half of the population is still at risk of tobacco-associated cancers. Therefore risk-adaptive cancer screening strategies are being evaluated not only for lung cancer but also for the detection of early asymptomatic GI cancers [11, 12]. Special attention should be paid to synergistic carcinogenic effects of coincident risk factors such as tobacco plus alcohol. Patients exposed to various, synergistically acting carcinogens can have an up to 100-fold increased risk for certain GI cancers [13, 14, 15].

Esophageal Squamous Cell Cancer

The use of tobacco, including cigarettes, cigars, pipes, and chewing tobacco, is a major risk factor for esophageal squamous cell cancer (ESCC). The more and the longer a person smokes, the higher the ESCC risk. When tobacco use goes along with alcohol consumption, ESCC risk rises synergistically [15, 16], see (Fig. 1). The majority of drinkers do smoke. Smoking cessation time-dependently decreases ESCC risk, particularly in Western populations [17].

Fig. 1.

Combined exposure to both cigarette smoking and alcohol use and risk of developing ESCC. Alcohol (ethanol) consumption is given in milliliters of pure alcohol drunk per day. The material has been reproduced from [15]. OR, odds ratio; CI, confidence interval.

Persons exposed to synergistically acting carcinogens for more than 15–20 years may consider going for a screening esophagoscopy as to detect precancerous lesions and asymptomatic early ESCC. Male smokers with risky alcohol use should have access to screening esophagogastroscopy at the age of 50 years. Former smokers surviving a lung or head and neck cancer should be surveilled endoscopically for a second primary ESCC [16]. Risk prediction models for esophageal cancer among the general population and biomarkers for early detection are being evaluated [18, 19].

Gastric Cancer

Gastric cancer (GC) is the third leading cause of cancer deaths worldwide. Smoking tobacco is the most important behavioral risk factor for GC. Several studies have examined the relationship between tobacco use and GC. A meta-analysis estimated that the risk was increased about 1.5-fold and was higher in men. Risks are somewhat higher for cardia than noncardia GC. When tobacco smoking goes along with (CagA-positive) Helicobacter pylori infection, the risk for GC can increase synergistically [20, 21]. About 18% of GC cases and 21% of GC deaths may be attributed to smoking [3, 4]. Important to note, GC risk decreases with increasing time since stopping cigarette smoking and becomes similar to that of never smokers 10 years after quitting [22].

In addition, H. pylori infection, family history, diabetes, dietary (nitroso compounds and a high-salt diet with few vegetables), or lifestyle factors (excess body weight, physical inactivity, and alcohol use) as well as chronic atrophic gastritis are important risk factors of GC. All these risk factors should be taken into account when counseling a smoker whether and at what age to go for a screening esophagogastroduodenoscopy. The Korean National Cancer Screening Program has provided strong evidence that screening gastroscopy offered to the general population − starting at the age of 40 years − effectively reduces both GC and overall mortality [23]. Although early-detection screening is routine in Korea, Japan, and certain areas of China [23, 24, 25], in Western countries, screening esophagogastroscopy is restricted to persons at high risk.

Smokers who show 4 or more risk factors of esophageal and/or GC are at high risk of upper GI cancer and should be advised to go for a screening esophagogastroscopy at the age of 50 years. The aim is to detect early esophageal cancer, early esophagogastric junction adenocarcinoma, early GC, or precancerous lesions. Risk factors of GC are H. pylori infection, dietary (nitroso compounds and high-salt diet with few vegetables), and lifestyle factors (excess body weight, tobacco smoking, and risky alcohol use), family history, age, male sex, diabetes, and autoimmune gastritis/pernicious anemia. Well-known risk factors of (either squamous or glandular cell) esophageal cancer comprise tobacco use, risky alcohol intake, family history, (previous) head and neck cancer, age, male sex, excess body weight, Barrett's esophagus, reflux disease, and diabetes.

Hepatocellular Cancer

A nested case-control study in Europe showed that smoking tobacco contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively [26]. Tobacco use increases hepatocellular cancer (HCC) risk dose-dependently (see Fig. 2a). Various carcinogens can interact synergistically to cause HCC. The combination of tobacco smoking with excess body weight, alcohol use, or chronic hepatitis B or C infection can lead to overadditive HCC risks [27, 28, 29, 30]. Thus, obese smokers with concomitant diabetes and chronic hepatitis B or C infection are at a 100-fold increased risk of HCC [14]. Patients at high risk should go for liver ultrasound every 6 months as to detect early HCC. Important to note, HCC risk decreases after quitting smoking [7]. About 22% of liver cancer deaths in the USA could be prevented by not smoking [3].

Fig. 2.

Cubic spline graph of the multivariate-adjusted HR (represented by the solid line) and 95% CI (represented by the dotted lines) for the association between smoking intensity and HCC (a) and ICC risk (b) in the Liver Cancer Pooling Project (knots: 0.5, 10, 15, and 25; referent: 0). This material has been reproduced from [30]. HCC, hepatocellular cancer; ICC, intrahepatic cholangiocarcinoma.

Biliary Tract Cancer

Smokers have increased risk of intrahepatic (hazard ratio [HR] = 2.15; 95% confidence interval [CI] = 1.15–4.00, in case of >40 cigarettes/day) and extrahepatic cholangiocarinoma (HR = 1.69; 95% CI = 1.34–2.13) compared with nonsmokers. While smoking tobacco is associated with both intrahepatic (see Fig. 2b) and extrahepatic bile ducts as well as ampulla of Vater cancers (HR = 2.22; 95% CI = 1.69–2.92), a causal link with gallbladder cancer remains ambiguous [31].

Pancreatic Cancer

Cigarette smoking increases the risk for pancreatic cancer (PC), and the estimated population-attributable fraction of PC deaths to tobacco smoking is 11–32 percent [3, 32]. In multiple cohort and case-control studies, the relative risk for developing PC among smokers was about twice. PC risk increases up to 5-fold with the amount of cigarettes consumed [33]. Important to note, excess PC risk decreases with smoking cessation [7, 32]. It has been estimated that cessation of smoking could eliminate approximately 25 percent of PC cancer deaths in the USA.

Especially for people who have other risk factors like a family history of PC, risky alcohol use, excess body weight, chronic pancreatitis, or diabetes, it is crucial to quit smoking. There are synergistic interactions of tobacco smoking and alcohol use on the risk of PC [13]. Special attention should be paid to the smoking and drinking habits of young adults [34, 35].

Pancreatic adenocarcinoma has shown some of the most troubling signs of increase among young US adults. From 1995 to 2014, the average annual percent change in PC incidence increased with decreasing age from 0.77% (95% CI: 0.57–0.98) for the ages of 45–49 years to 2.47% (1.77–3.8) for the ages of 30–34 years and 4.34% (3.19–5.50) for the ages of 25–29 years [36]. Many experts blame the excess body weight epidemic, while others refer to altered intestinal microbiota, physical inactivity, diabetes mellitus, poor diet, risky alcohol use, and sedentary lifestyle. To what extent the recent smoking and drinking habits of young adults possibly contribute to the observed epidemiological changes still need to be investigated in more detail.

In the average population, there are to date no effective means available for the early detection of asymptomatic early-stage pancreatic adenocarcinoma. For the time being, not smoking and keeping a normal weight are the best options to significantly reduce the burden of PC deaths.

Colorectal Cancer

Cigarette smoking has been associated with increased incidence and mortality from colorectal cancer (CRC). A meta-analysis of 106 observational studies estimated that the risk of developing CRC was increased among cigarette smokers compared with those who never smoked (HR = 1.18, 95% CI = 1.11–1.25). Ever smoking explains about 11% of the CRC burden. The risk of dying from CRC is increased among smokers [37]. CRC risk factor attribution varies by the anatomic site. Thus, history of smoking is associated with left-sided CRC in a positive dose-response relationship [38, 39].

Ever and current smoking goes along with higher risk for certain molecular subtypes of CRC, especially with MSI-high, BRAF-mut, KRAS-wt, and CIMP-high CRC. In addition, tobacco use is associated with higher risk of CRC developing via the traditional or the serrated pathways [40].

Not only smoking but also age, sex, family history, risky alcohol use, diabetes, excess body weight, physical inactivity, poor diet, and ulcerative colitis are risk factors for sporadic CRC and have to be considered in risk-adaptive CRC screening strategies. Studies and models evaluating risk-adapted screening are still rare but suggest that risk-adapted CRC screening is more effective and efficient than conventional screening [11, 12].

Anal Cancer

Smoking increases the risk of anal cancer. The higher a person's pack-year history of smoking, the higher their risk of developing anal cancer. People who currently smoke are more likely to have cancer of the anus compared with people who do not smoke or have quit smoking [41]. Stopping tobacco use reduces the excess risk of developing anal cancer.

Preventive Oncology

A low-risk lifestyle can reduce GI cancer risk by as much as 50% [6]. Therefore, we should pursue a healthy lifestyle that includes following a prudent diet and avoiding excess body weight, pursuing an active exercise program, minimizing alcohol intake, and refraining from smoking tobacco.

It can be hard to quit smoking, but the chances of succeeding are drastically increased with the right support [42, 43, 44]. In several countries, there are comprehensive tobacco cessation programs that use recognized and evidence-based cessation aids. In Ireland, smokers are twice as likely to succeed in ending tobacco addiction with the help of national tobacco cessation programs and 4 times more likely with a combination of cessation programs and medication. Ireland now has more quitters than smokers [42]. The tobacco control measures implemented in Denmark, Norway, Sweden, and Finland have succeeded in lowering the percentage of daily smokers by about 50% [43]. As tobacco use is the most preventable cause of cancer deaths, effective tobacco control does reduce the burden of GI cancer significantly.

Conflict of Interest Statement

The author has no conflicts of interest to declare.

Funding Sources

This work was not funded.

Author Contributions

H.S. designed and wrote the manuscript.