Cancer rates among patients with hepatitis C are increased compared to those not infected

Public Release: 24-Apr-2015

Researchers suggest an extrahepatic manifestation of hepatitis C may be an increased risk of cancer

European Association for the Study of the Liver

April 24, 2015, Vienna , Austria: Results announced today at The International Liver CongressTM 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer.

The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin's lymphoma, renal and prostate cancers, as well as liver cancer.

A retrospective study at Kaiser Permanente, Southern California, USA, was conducted. The study authors recorded all cancer diagnoses in patients over 18 years of age with or without HCV during 2008-2012. Within the timeframe of the study 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non-HCV cohort.

In the HCV cohort there were 2,213 cancer diagnoses (1,524/100,000) during the 5-year period and 1,654 cancer diagnoses when liver cancer was excluded (1,139/100,000). In the non-HCV cohort there were 84,419 cancer diagnoses (605/100,000) during the same 5-year period and 83,795 (601/100,000) when liver cancer was excluded. When all cancers are considered the rate is 2.5 times higher in the HCV cohort; when liver cancers are excluded, the rate is still almost 2 times higher.

Lisa Nyberg, MD, MPH, Kaiser Permanente, Southern California, senior author of the study, explains: "The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers. These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer. However, the findings must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results."

Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver, commented: "This data adds to the evidence bank linking hepatitis C with an increased risk of cancer, and highlights that there is still a long way to go in order to fully understand this complex and devastating disease."

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About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL

Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact

For more information, please contact the ILC Press Office at:

ilc.press@easloffice.eu or
+44 (0)20 3580 5444

INCREASED CANCER RATES IN PATIENTS WITH CHRONIC HEPATITIS C: AN ANALYSIS OF THE CANCER REGISTRY IN A LARGE U.S. HEALTH MAINTENANCE ORGANIZATION

Anders H. Nyberg* 1, Joanie W. Chung2, Jiaxiao M. Shi3, T. C. Cheetham3, Kevin M. Chiang4, Reina Haque5, Zobair M. Younossi6, Lisa M. Nyberg1

1Gastroenterology/Hepatology, Kaiser Permanente, San Diego, 2Kaiser Permanete, Research and Evaluation, 3Research and Evaluation, Kaiser Permanente, Pasadena, 4Pharmacy Analytical Services, Kaiser Permanente, Downey, 5Research and Evaluatuion, Kaiser Permanente, Pasadena, 6Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, United States

Background and Aims: Hepatitis C virus (HCV) is an oncogenic virus, and an increased risk of malignancy in HCV has previously been reported. Cancer types associated with HCV include non-Hodgkin's lymphoma, renal and prostate cancers; as well as liver cancer. The aim of this study was to describe cancer rates in our cohort of HCV patients compared to cancer rates in the non-HCV population.

Methods: This is a retrospective study at Kaiser Permanente Southern California (KPSC), a large health maintenance organization with 3.5-4 million members. The KPSC cancer registry is an accredited program maintaining a complete profile of all cancer diagnoses for all KP members. In this study, we recorded all cancer diagnoses in patients ?18 years of age with or without HCV during 2008-2012.

Results: From 2008 to 2012, 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non HCV cohort. Mean age at cancer diagnosis in the HCV cohort was 61.8 years, in the non-HCV cohort, 63.5 years. In the HCV cohort there were 2,213 cancer diagnoses (1524/100000) during the 5 year period and 1,654 cancer diagnoses when liver cancer was excluded (1139/100000). In the non HCV cohort there were 84,419 cancer diagnoses (605/100000) during the same 5 year period and 83,795 (601/100000) when liver cancer was excluded. The rate ratios between the HCV and non HCV cohorts for the total number of cancer cases including and excluding liver cancer are shown in Table 1.

Conclusions: In our cohort of Hepatitis C infected patients, cancer rates were significantly increased compared to the non-HCV cohort. This suggests that another extrahepatic manifestation of HCV may be an increased risk of cancer.

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New drug combo causes cancer cells to 'eat themselves'

PTI Nov 6, 2013, 03.59PM IST

WASHINGTON: A new drug combination therapy could effectively kill colon, liver, lung, kidney, breast and brain cancer cells without affecting the healthy cells, scientists say.

The results from a recent preclinical study at Virginia Commonwealth University Massey Cancer Center lays the foundation to plan a future phase 1 clinical trial to test the safety of the therapy in a small group of patients.

"It is still too premature to estimate when a clinical trial will open to further test this drug combination therapy, but we are now in the planning phase and encouraged by the results of these laboratory experiments," said Andrew Poklepovic, assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine.

The study led by Paul Dent demonstrated that the drugs sorafenib and regorafenib synergise with a class of drugs known as PI3K/AKT inhibitors to kill a variety of cancers.

Sorafenib and regorafenib work by blocking the production of enzymes called kinases, which are vital to the growth and survival of cancer cells.

Sorafenib is currently approved by the FDA to treat kidney and liver cancers, and regorafenib is currently approved for the treatment of colorectal cancer.

However, sorafenib and regorafenib do not directly affect PI3K and AKT kinases, which are also very active in promoting cancer cell survival.

The addition of a PI3K/AKT inhibitor to the combination of sorafenib and regorafenib dramatically increased cell death and was even effective against cells with certain mutations that make one or the other drug less effective.

"We know that there are certain cellular processes that are frequently dysregulated in cancers and important to cell proliferation and survival, but if you shut down one, then cells can often compensate by relying on another," said Dent.

"We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive," Dent said.

Results showed that the combination therapy killed the cells by physically interacting with molecules to block the survival pathways and induce a toxic effect known as autophagy.

Autophagy is a protective process where cells metabolise themselves when starved of the resources needed to survive.

The study was published in the journal Molecular Pharmacology.

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Alcohol and Cancer Risk (Fact Sheet)

Provided by OncologyNurseAdvisor

October 28, 2013

What is alcohol?

Alcohol is the common term for ethanol or ethyl alcohol, a chemical substance found in beer, wine, and liquor, as well as in some medicines, mouthwashes, household products, and essential oils (scented liquids taken from plants). Alcohol is produced by the fermentation of sugars and starches by yeast.

The main types of alcoholic drinks and their alcohol content are as follows:

• Beers and hard ciders: 3-7 percent alcohol
• Wines, including sake: 9-15 percent alcohol
• Wines fortified with liquors, such as port: 16-20 percent alcohol

Liquor, or distilled spirits, such as gin, rum, vodka, and whiskey, which are produced by distilling the alcohol from fermented grains, fruits, or vegetables: usually 35-40 percent alcohol (70-80 proof), but can be higher

According to the National Institute on Alcohol Abuse and Alcoholism, a standard alcoholic drink in the United States contains 14.0 grams (0.6 ounces) of pure alcohol. Generally, this amount of pure alcohol is found in

• 12 ounces of beer
• 8 ounces of malt liquor
• 5 ounces of wine
• 1.5 ounces or a "shot" of 80-proof liquor

The federal government's Dietary Guidelines for Americans 2010 defines moderate alcohol drinking as up to one drink per day for women and up to two drinks per day for men. Heavy alcohol drinking is defined as having more than three drinks on any day or more than seven drinks per week for women and more than four drinks on any day or more than 14 drinks per week for men.

What is the evidence that alcohol drinking is a cause of cancer?

Based on extensive reviews of research studies, there is a strong scientific consensus of an association between alcohol drinking and several types of cancer (1, 2). In its Report on Carcinogens, the National Toxicology Program of the US Department of Health and Human Services lists consumption of alcoholic beverages as a known human carcinogen. The research evidence indicates that the more alcohol a person drinks—particularly the more alcohol a person drinks regularly over time—the higher his or her risk of developing an alcohol-associated cancer. Based on data from 2009, an estimated 3.5 percent of all cancer deaths in the United States (about 19,500 deaths) were alcohol related (3).

Clear patterns have emerged between alcohol consumption and the development of the following types of cancer:

• Head and neck cancer: Alcohol consumption is a major risk factor for certain head and neck cancers, particularly cancers of the oral cavity (excluding the lips), pharynx (throat), and larynx (voice box) (4). People who consume 50 or more grams of alcohol per day (approximately 3.5 or more drinks per day) have at least a two to three times greater risk of developing these cancers than nondrinkers (4). Moreover, the risks of these cancers are substantially higher among persons who consume this amount of alcohol and also use tobacco (5).

• Esophageal cancer: Alcohol consumption is a major risk factor for a particular type of esophageal cancer called esophageal squamous cell carcinoma (2). In addition, people who inherit a deficiency in an enzyme that metabolizes alcohol have been found to have substantially increased risks of alcohol-related esophageal squamous cell carcinoma (see

• Liver cancer: Alcohol consumption is an independent risk factor for, and a primary cause of, liver cancer (hepatocellular carcinoma) (6). (Chronic infection with hepatitis B virus and hepatitis C virus are the other major causes of liver cancer.)

• Breast cancer: More than 100 epidemiologic studies have looked at the association between alcohol consumption and the risk of breast cancer in women. These studies have consistently found an increased risk of breast cancer associated with increasing alcohol intake. A meta-analysis of 53 of these studies (which included a total of 58,000 women with breast cancer) showed that women who drank more than 45 grams of alcohol per day (approximately three drinks) had 1.5 times the risk of developing breast cancer as nondrinkers (a modestly increased risk) (7). The risk of breast cancer was higher across all levels of alcohol intake: for every 10 grams of alcohol consumed per day (slightly less than one drink), researchers observed a small (7 percent) increase in the risk of breast cancer. 

The Million Women Study in the United Kingdom (which included more than 28,000 women with breast cancer) provided a more recent, and slightly higher, estimate of breast cancer risk at low to moderate levels of alcohol consumption: every 10 grams of alcohol consumed per day was associated with a 12 percent increase in the risk of breast cancer (8).

• Colorectal cancer: Alcohol consumption is associated with a modestly increased risk of cancers of the colon and rectum. A meta-analysis of 57 cohort and case-control studies that examined the association between alcohol consumption and colorectal cancer risk showed that people who regularly drank 50 or more grams of alcohol per day (approximately 3.5 drinks) had 1.5 times the risk of developing colorectal cancer as nondrinkers or occasional drinkers (9). For every 10 grams of alcohol consumed per day, there was a small (7 percent) increase in the risk of colorectal cancer.

Research on alcohol consumption and other cancers:

Numerous studies have examined the association between alcohol consumption and the risk of other cancers, including cancers of the pancreas, ovary, prostate, stomach, uterus, and bladder. For these cancers, either no association with alcohol use has been found or the evidence for an association is inconsistent. 

However, for two cancers—renal cell (kidney) cancer and non-Hodgkin lymphoma (NHL)—multiple studies have shown that increased alcohol consumption is associated with a decreased risk of cancer (10, 11). A meta-analysis of the NHL studies (which included 18,759 people with NHL) found a 15 percent lower risk of NHL among alcohol drinkers compared with nondrinkers (11). The mechanisms by which alcohol consumption would decrease the risks of either renal cell cancer or NHL are not understood.

How does alcohol increase the risk of cancer?

Researchers have identified multiple ways that alcohol may increase the risk of cancer, including:

• ametabolizing (breaking down) ethanol in alcoholic drinks to acetaldehyde, which is a toxic chemical and a probable human carcinogen; acetaldehyde can damage both DNA (the genetic material that makes up genes) and proteins (see Question 5)
• generating reactive oxygen species (chemically reactive molecules that contain oxygen), which can damage DNA, proteins, and lipids (fats) through a process called oxidation
• impairing the body's ability to break down and absorb a variety of nutrients that may be associated with cancer risk, including vitamin A; nutrients in the vitamin B complex, such as folate; vitamin C; vitamin D; vitamin E; and carotenoids
• increasing blood levels of estrogen, a sex hormone linked to the risk of breast cancer

Alcoholic beverages may also contain a variety of carcinogenic contaminants that are introduced during fermentation and production, such as nitrosamines, asbestos fibers, phenols, and hydrocarbons.

How does the combination of alcohol and tobacco affect cancer risk?

Epidemiologic research shows that people who use both alcohol and tobacco have much greater risks of developing cancers of the oral cavity, pharynx (throat), larynx, and esophagus than people who use either alcohol or tobacco alone. In fact, for oral and pharyngeal cancers, the risks associated with using both alcohol and tobacco are multiplicative; that is, they are greater than would be expected from adding the individual risks associated with alcohol and tobacco together (5, 12).

Can a person's genes affect their risk of alcohol-related cancers?

A person's risk of alcohol-related cancers is influenced by their genes, specifically the genes that encode enzymes involved in metabolizing (breaking down) alcohol (13).

For example, one way the body metabolizes alcohol is through the activity of an enzyme called alcohol dehydrogenase, or ADH. Many individuals of Chinese, Korean, and especially Japanese descent carry a version of the gene for ADH that codes for a "superactive" form of the enzyme. This superactive ADH enzyme speeds the conversion of alcohol (ethanol) to toxic acetaldehyde. As a result, when people who have the superactive enzyme drink alcohol, acetaldehyde builds up. Among people of Japanese descent, those who have this superactive ADH have a higher risk of pancreatic cancer than those with the more common form of ADH (14).

Another enzyme, called aldehyde dehydrogenase 2 (ALDH2), metabolizes toxic acetaldehyde to non-toxic substances. Some people, particularly those of East Asian descent, carry a variant of the gene for ALDH2 that codes for a defective form of the enzyme. In people who have the defective enzyme, acetaldehyde builds up when they drink alcohol. The accumulation of acetaldehyde has such unpleasant effects (including facial flushing and heart palpitations) that most people who have inherited the ALDH2 variant are unable to consume large amounts of alcohol. Therefore, most people with the defective form of ALDH2 have a low risk of developing alcohol-related cancers.

However, some individuals with the defective form of ALDH2 can become tolerant to the unpleasant effects of acetaldehyde and consume large amounts of alcohol. Epidemiologic studies have shown that such individuals have a higher risk of alcohol-related esophageal cancer, as well as of head and neck cancers, than individuals with the fully active enzyme who drink comparable amounts of alcohol (15). These increased risks are seen only among people who carry the ALDH2 variant and drink alcohol—they are not observed in people who carry the variant but do not drink alcohol.

Can drinking red wine help prevent cancer?

Researchers conducting studies using purified proteins, human cells, and laboratory animals have found that certain substances in red wine, such as resveratrol, have anticancer properties (16). Grapes, raspberries, peanuts, and some other plants also contain resveratrol. However, clinical trials in humans have not provided evidence that resveratrol is effective in preventing or treating cancer (17). Few epidemiologic studies have looked specifically at the association between red wine consumption and cancer risk in humans. 

What happens to cancer risk after a person stops drinking alcohol?

Most of the studies that have examined whether cancer risk declines after a person stops drinking alcohol have focused on head and neck cancers and on esophageal cancer. In general, these studies have found that stopping alcohol consumption is not associated with immediate reductions in cancer risk; instead, it may take years for the risks of cancer to return to those of never drinkers.

For example, a pooled analysis of 13 case-control studies of cancer of the oral cavity and pharynx combined found that alcohol-associated cancer risk did not begin to decrease until at least 10 years after stopping alcohol drinking. Even 16 years after they stopped drinking alcohol, the risk of cancer was still higher for ex-drinkers than for never drinkers (18).

In several studies, the risk of esophageal cancer was also found to decrease slowly with increasing time since stopping alcohol drinking. A pooled analysis of five case–control studies found that the risk of esophageal cancer did not approach that of never drinkers for at least 15 years after stopping alcohol drinking (18).

Is it safe for someone to drink alcohol while undergoing cancer chemotherapy?

As with most questions related to a specific individual's cancer treatment, it is best for a patient to check with their health care team about whether or not it is safe to drink alcohol during or immediately following chemotherapy treatment. The doctors and nurses administering the treatment will be able to give specific advice about whether drinking alcohol is safe with particular chemotherapy drugs and/or other medications prescribed along with chemotherapy.

Selected References

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Alcohol consumption and ethyl carbamate Exit Disclaimer. IARC Monographs on the Evaluation of Carcinogenic Risks in Humans 2010;96:3-1383.

2. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. Exit Disclaimer IARC Monographs on the Evaluation of Carcinogenic Risks in Humans 2012;100(Pt E):373-472.

3. Nelson DE, Jarman DW, Rehm J, et al. Alcohol-attributable cancer deaths and years of potential life lost in the United States. American Journal of Public Health 2013;103(4):641-648.

4. Baan R, Straif K, Grosse Y, et al. Carcinogenicity of alcoholic beverages Exit Disclaimer. Lancet Oncology 2007;8(4):292-293.

5. Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiology, Biomarkers & Prevention 2009;18(2):541-550.

6. Grewal P, Viswanathen VA. Liver cancer and alcohol. Clinics in Liver Disease 2012;16(4):839-850.

7. Hamajima N, Hirose K, Tajima K, et al. Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. British Journal of Cancer 2002;87(11):1234-1245.

8. Allen NE, Beral V, Casabonne D, et al. Moderate alcohol intake and cancer incidence in women. Journal of the National Cancer Institute 2009;101(5):296-305.

9. Fedirko V, Tramacere I, Bagnardi V, et al. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Annals of Oncology 2011;22(9):1958-1972.

10. Bellocco R, Pasquali E, Rota M, et al. Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis. Annals of Oncology 2012;23(9):2235-2244.

11. Tramacere I, Pelucchi C, Bonifazi M, et al. A meta-analysis on alcohol drinking and the risk of Hodgkin lymphoma. European Journal of Cancer Prevention 2012;21(3):268-273.

12. Turati F, Garavello W, Tramacere I, et al. A meta-analysis of alcohol drinking and oral and pharyngeal cancers: results from subgroup analyses. Alcohol and Alcoholism 2013;48(1):107-118.

13. Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncology 2009;10(2):173-180.

14. Kanda J, Matsuo K, Suzuki T, et al. Impact of alcohol consumption with polymorphisms in alcohol-metabolizing enzymes on pancreatic cancer risk in Japanese. Cancer Science 2009;100(2):296-302.

15. Yokoyama A, Omori T. Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers Exit Disclaimer. Alcohol 2005;35(3):175-185.

16. Athar M, Back JH, Tang X, et al. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicology and Applied Pharmacology 2007;224(3):274-283.

17. Patel KR, Scott E, Brown VA, et al. Clinical trials of resveratrol. Annals of the New York Academy of Sciences 2011;1215:161-169.

18. Rehm J, Patra J, Popova S. Alcohol drinking cessation and its effect on esophageal and head and neck cancers: a pooled analysis. International Journal of Cancer 2007;121(5):1132-1137.

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HIV drugs may get new role in fighting cancer

By Ben Hirschler

Fri Oct 25, 2013 3:07pm EDT

(Reuters) - A type of HIV medicine that stops the AIDS virus from entering immune system cells could in future be put to work against cancer in new combination therapies being developed by drug companies.

Interest in using so-called CCR5 inhibitors to fight tumors was fuelled last year when U.S. researchers, testing the drugs on mice, reported a marked reduction in aggressive breast cancer cells spreading to the animals' lungs.

Researchers from the Thomas Jefferson University Kimmel Cancer Center described the results as "dramatic" after they were published in the Journal of Cancer Research.

Now industry analysts at Citi believe Merck & Co Inc is set to take things to the next stage by testing its CCR5 drug vicriviroc in cancer patients. The product was abandoned as a treatment for HIV in 2010 following an unsuccessful study.

Pfizer Inc and Bristol-Myers Squibb - which also have similar drugs in their portfolios - could follow suit, Citi said in a note on Friday.

Asked to comment on the suggestion that it would start testing vicriviroc in patients in 2014 as part of a combination therapy for cancer, a spokesman for Merck said: "We have not disclosed any such plans."

Citi said it expected vicriviroc to re-enter clinical testing in combination with cancer immunotherapy as Merck explores its potential across multiple tumor types, including melanoma, colorectal, breast, prostate and liver cancer.

Immunotherapy, which harnesses the body's immune system to fight cancer, is a hot new area for cancer research, with some experts predicting the approach will in future form the backbone of many cancer treatments.

However, drug combinations are expected to be critical to its success as oncologists will need to block cancer cells on several fronts at once.

One option is to combine two immunotherapies, while another approach, also being pursued by other companies like Roche Holding AG and AstraZeneca Plc, is to combine immunotherapy medicines with different drug types.

CCR5 inhibitors are one such option, given the encouraging signals from pre-clinical research. As these drugs have already been studied in HIV, their development could be relatively rapid.

Pfizer could also start clinical trials in cancer with its approved CCR5 drug Selzentry, which is currently marketed for HIV via the ViiV Healthcare alliance with GlaxoSmithKline Plc and Shionogi & Co Ltd.

Bristol, meanwhile, has a dual CCR2/5 inhibitor in mid-stage Phase II development, which is being tested for diabetes and kidney disease.

(Editing by Patrick Lannin)

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