Tobacco.org

Joe Caridi: Not just a "smoker's disease" 

I want to thank you for your article about Caren Gorenberg and her struggle with lung cancer as a non-smoker. Caren's fight is one that I am very familiar with as my wife of 10 years, Dianne, is an 18-month survivor of lung cancer.

She is only 40 years old and is a life-long non-smoker. Dianne and I have learned much about lung cancer in the last year and a half and have been surprised as many of your readers were to learn that lung cancer hits non-smokers as well a life-long smokers in devastating numbers.

In fact, if lung cancer in never-smokers were classified as its own disease, it would rank as the 6th deadliest cancer in the U.S. . . .

I believe that the biggest problem facing lung cancer patients today is that most people believe that it is still a smoker's disease. And smokers somehow deserve to get cancer.

Jump to full article »

Gainesville nonsmoker with genetic mutation embarks on lung cancer crusade  

Caren Gorenberg couldn't believe it when she was told the news in late 2006. She had a mass in her lung. It was cancer.

"I had no signs ... not a symptom. I was feeling great. I had no clue that anything could possibly be wrong," she said.

"Everybody always asks immediately, 'Did you smoke?' " Gorenberg said.

The 67-year-old mother of four is not a smoker, yet she has been diagnosed with one of the most virulent forms of lung cancer. Now she is making it her personal cause to spread the word about lung cancer. It is increasingly showing up in women, particularly in non-smokers. . . .

Tarceva has proven particularly effective with patients who have Gorenberg's Exon 21 genetic mutation. . . .

"When I first went to the Internet, I didn't find much in the way of hope. Everything seemed to say, 'If you get this, you die,' " Gorenberg said.

While contacting research institutions and doctors internationally, Jamie Gorenberg discovered the Bonnie J. Addario Foundation.

Jump to full article »

Genetic Variant Raises Lung Cancer Risk  

People with a particular genetic trait are at much higher risk of developing lung cancer from exposure to secondhand smoke than others, even if they rarely come into contact with it, a new study finds.

Researchers also found that smokers with this variant are more susceptible to lung cancer, whether they light up a lot or a little.

"If you carried the inherited risk and then you smoked, it didn't matter if you were a light smoker or a heavy smoker -- you were significantly more likely to develop lung cancer," study co-investigator Susan Pinney, an associate professor in the department of environmental health at the University of Cincinnati, said in a news release from the school.

Jump to full article »

A Susceptibility Locus on Chromosome 6q Greatly Increases Lung Cancer Risk among Light and Never Smokers  

Cigarette smoking is the major cause for lung cancer, but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk. To characterize the effects that this region of chromosome 6q region has on lung cancer risk, we identified a haplotype that segregated with lung cancer. We then performed Cox regression analysis to estimate the differential effects that smoking behaviors have on lung cancer risk according to whether each individual carried a risk-associated haplotype or could not be classified and was assigned unknown haplotypic status. We divided smoking exposures into never smokers, light smokers (<20 pack-years), moderate smokers (20 to <40 pack-years), and heavy smokers (40 pack-years). Comparing results according to smoking behavior stratified by carrier status, compared with never smokers, there was weakly increasing risk for increasing smoking behaviors, with the hazards ratios being 3.44, 4.91, and 5.18, respectively, for light, moderate, or heavy smokers, whereas among the individuals from families without the risk haplotype, the risks associated with smoking increased strongly with exposure, the hazards ratios being, respectively, 4.25, 9.17, and 11.89 for light, moderate, and heavy smokers. The never smoking carriers had a 4.71-fold higher risk than the never smoking individuals without known risk haplotypes. These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers.

Jump to full article »

• Genetic variant greatly increases lung cancer risk for light smokers 

Individuals with a certain type of genetic susceptibility to lung cancer face a greatly increased risk for the deadly disease with even a small exposure to cigarette smoke, a study team that includes researchers from the University of Cincinnati (UC) has concluded.

For family members who carry this genetic variant, the risk of lung cancer is similar for both light and heavy smokers, the researchers say, adding that even non-smokers who are exposed to second-hand cigarette smoke and have a family history of lung cancer should be monitored for early detection.

The study, conducted by the Genetic Epidemiology of Lung Cancer Consortium (GELCC), is being published online March 9, 2010, ahead of print by Cancer Research, a publication of the American Association for Cancer Research. Print date is March 15.

Jump to full article »

Smoking significantly increases risk of aneurysm in people with certain genes  

For people who carry common gene variants, cigarette smoking greatly increases the risk that a blood vessel in the brain will weaken and balloon out -- called an aneurysm -- which could be life-threatening if it ruptures, according to research presented at the American Stroke Association's International Stroke Conference 2010.

Researchers reported on two new studies from the Familial Intracranial Aneurysm (FIA) project, a multinational collaboration funded by the National Institutes of Neurological Disorders and Stroke to study genetic and other risk factors in families with at least two members affected by intracranial aneurysm.

Jump to full article »

Taiwan study proves relation between tobacco, lung cancer 

A Taiwanese research had further identified the reason why tobacco causes lung cancer and other smoking-related diseases and was made the cover story of the February issue of the world is leading biomedical journal, The Journal of Clinical Investigation.

The study revealed the mechanism of how tobacco-specific carcinogen causes lung tumors. It showed that the key ingredient of tobacco carcinogen, nicotine-derived nitrosamine ketone (NNK), would induce the accumulation of a protein, DNA methyltranferase 1 (DNMT1), which inhibits the tumor suppressor genes, and lead to lung cancer.

It also showed that the accumulation of DNMT1 in lung cancer patients who smoked continuously correlates with poor recovery.

Jump to full article »

Researchers Explain How Tobacco Carcinogen NNK Triggers Lung Tumors. 

The tobacco-specific carcinogen NNK may promote lung-tumor formation and development by inducing the accumulation of the DNA methyltransferase 1 (DNMT1) protein in the nucleus, report researchers from National Cheng Kung University, Taiwan. They explain that DNMT1 silences genes that suppress tumor formation.

The study, appearing in the January 19 edition of The Journal of Clinical Investigation, is titled "The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients."

DNMT1 catalyzes DNA methylation and is overexpressed in many human diseases including cancer. NNK also induces DNA methylation, however, the role of DNMT1-mediated methylation in tobacco carcinogenesis has remained unclear.

In this study, the scientists found that in a human lung cell line, glycogen synthase kinase 3β (GSK3β) phosphorylated DNMT1 to recruit β-transducin repeat-containing protein (βTrCP). This resulted in DNMT1 degradation. NNK activated AKT, inhibiting GSK3β function and thereby attenuating DNMT1 degradation.

The authors also found that NNK induced βTrCP translocation to the cytoplasm, resulting in DNMT1 accumulation in the nucleus as well as hypermethylation of tumor-suppressor gene promoters.

Jump to full article »

Researchers Uncover Mechanism of Tobacco Carcinogen. 

A group of investigators has discovered that nicotine-derived nitrosamine ketone (NNK), a tobacco carcinogen, not only causes DNA and genetic alteration but also induces epigenetic alterations in the process of cancer formation, inhibiting tumor suppressor genes.

The findings appear in a paper titled "The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients," published in The Journal of Clinical Investigation. The research team was led by Yi-Ching Wang, Ph.D., department of pharmacology, National Cheng Kung University.

DNA methyltransferase 1 (DNMT1) catalyzes DNA methylation and is overexpressed in many human diseases including cancer. The tobacco-specific carcinogen NNK also induces DNA methylation. The role of DNMT1-mediated methylation in tobacco carcinogenesis, however, remains unclear.

To better understand this mechanism, the researchers used human and mouse lung cancer samples and cell lines to determine how NNK induced DNMT1 expression and activity and triggered the inhibition of tumor suppressor genes.

Jump to full article »

A Rigorous and Comprehensive Validation: Common Genetic Variations and Lung Cancer  

Conclusions: None of the five candidate SNPs in lung cancer risk can be confirmed in our study. The previously reported association could be explained by disparity in tobacco smoke exposure and chronic obstructive pulmonary disease history between cases and controls. Instead, we found rs4324798 to be an independent predictor in small cell lung cancer survival, warranting further elucidation of the underlying mechanisms.

Jump to full article »

• The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients 

DNMT1 overexpression strongly correlates with smoking status and poor prognosis of lung cancer patients. . . .

NNK increases DNMT1 protein expression and activity. . . .

NNK prolongs DNMT1 protein stability through AKT signaling, which is associated with the ubiquitin-proteosome system. . . .

NNK activates AKT, then inhibits GSK3β/β-transducin repeat–containing protein–mediated protein degradation, leading to DNMT1 protein accumulation. . . .

NNK treatment enhances AKT downstream proteins, promotes hnRNP-U/βTrCP translocation to the cytoplasm, and induces DNMT1 accumulation in the nucleus . . .

NNK induces DNMT1, p-AKTser473, p-GSK3βser9, cytoplasmic hnRNP-U, and cytoplasmic βTrCP protein expression level in mouse lung adenoma tissues. . . .

DNMT1 and βTrCP interaction is disrupted in lung tumor tissue of patients who smoked.

Jump to full article »

Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes 

Jump to full article »

• Cigarettes May Cause Infections  

“Nearly every paper that you pick up discussing the health effects of cigarettes starts out with something to the effect that smokers and people exposed to secondhand smoke experience high rates of respiratory infections,” notes Amy Sapkota of the University of Maryland, College Park. The presumption has been that smoking renders people vulnerable to disease by impairing lung function or immunity. And it may well do both.

“But nobody talks about cigarettes as a source of those infections,” she says. Her new data now suggest that’s distinctly possible.

If these germs are alive, something she has not yet confirmed, just handling cigarettes or putting an unlit one to the mouth could be enough to cause an infection.

The idea that tobacco might contain viable germs isn’t just idle conjecture. Several research teams have isolated bacteria from tobacco that they could grow out in petri dishes. Those earlier investigations tended to hunt for — and, when found, attempted to grow — only one or two species of interest, Sapkota says. . . .

Several thousand potentially toxic chemicals have been isolated from cigarettes. Sapkota says that it’s not hard to imagine that the number of germs hosted by tobacco products could rival that of the carcinogens and other poisons residing in or produced by burning tobacco.

How so, when she’s only found genetic material indicting hundreds of germs? Owing to the bacterial probes available when Sapkota began her tobacco work, she was only able to screen for 700-odd species. But newer probes on the market can now screen for the bacterial 16S genetic material of 5,000 or more germs. And if she used such huge batteries of probes now, she said she fully expects she could turn up at least 1,000 hitchhiking bacterial species in tobacco products.

Jump to full article »

AACR-IASLC: Boffo Debut for Gene-Targeted Drug in NSCLC  

Action Points

* Caution interested patients that the investigational drug used in the study is not FDA approved and that its efficacy will need to be confirmed in the ongoing phase III trial.

* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

CORONADO, Calif. -- Non-small cell lung cancers linked to a specific genetic abnormality may be highly responsive to a novel drug that inhibits anaplastic lymphoma kinase (ALK), according to preliminary trial results reported here.

Among patients with rearrangements on the anaplastic lymphoma kinase (ALK) gene within the short arm of chromosome 2 of their lung tumors, 64% had an objective response to the ALK inhibitor PF-02341066.

The phase I study findings were presented at the Joint Conference on Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research-International Association for the Study of Lung Cancer.

Jump to full article »

EGFR gene signature predicts non-small cell lung cancer prognosis 

Epidermal growth factor receptor (EGFR) is a validated therapeutic target for non-small cell lung cancer. Researchers have now discovered a 93-gene signature that is associated with the presence of EGFR mutations in tumors from lung cancer patients and is a favorable prognostic marker in patients with early stage lung cancer.

"We hope this mutation signature will be able to define patients with these tumor types who will then respond to EGFR inhibition," said Pierre Saintigny, M.D., Ph.D., a research scientist at the University of Texas M. D. Anderson Cancer Center.

Data presented at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer have immediate clinical implications. The EGFR-mutation signature will be evaluated as a predictor of response in the BATTLE (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination) I trial, which will be presented later this year.

Jump to full article »