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November 3rd, 2016:

Exclusive: Global tobacco treaty leaders proposes ejecting delegates with ties to industry

By Duff Wilson and Aditya Kalra NEW YORK/NEW DELHI (Reuters) – The World Health Organization is about to get tough with the global tobacco industry.

Delegates at a conference next week on controlling tobacco with ties to the business could be refused credentials and ejected, according to an internal document seen by Reuters.

The proposal, if adopted by the full Framework Convention on Tobacco Control (FCTC) at the conference in India, could affect delegates sent by countries like China and Vietnam, where governments own cigarette companies or promote tobacco growing and have in the past sent representatives linked to the industry.

Any such members of the 180 delegations at the Nov. 7-12 conference near New Delhi “would be requested to leave the premises”, according to the Oct. 17 “note verbale”, an official diplomatic communication, from the WHO FCTC secretariat on behalf of the treaty’s leadership group to its parties.

At the last WHO FCTC conference, in Moscow in 2014, China’s 18-person delegation had four members from the “State Tobacco Monopoly Administration”.

At the 2012 conference, in Seoul, two of eight Vietnamese delegates were from the “Vietnam Tobacco Association”.

When asked about the letter, a Vietnamese government official who declined to be identified told Reuters there would be no industry representatives in their delegation.

China’s Ministry of Commerce did not immediately respond to a request for comment.

The proposed restriction highlights a growing battle between the industry and backers of the treaty, which went into effect in 2005 to guide national laws and policies in an effort to curb tobacco use, which kills an estimated 6 million people a year worldwide.

The global tobacco industry is estimated to be worth nearly $800 billion this year.

The International Tobacco Growers Association, a nonprofit group partly funded by big international cigarette companies, said the proposal was “beyond the wildest imagination”.

António Abrunhosa, chief executive of the group and a Portuguese tobacco grower, said in an email to Reuters that such a step was “unthinkable for a United Nations agency”.

John Stewart, deputy campaigns director at Corporate Accountability International, a Boston-based advocacy group that has supported tobacco-control efforts, praised the proposed restrictions.

“The tobacco industry has really forced parties and the secretariat into a corner,” he said in an interview.

“This is a bold good-government action to ensure that the treaty space, the place where public health policies will save millions of lives, is free of tobacco industry intimidation.”

Issues for debate at the conference include alternative livelihoods for tobacco farmers, e-cigarette regulation and trade and investment issues.

The secretariat earlier wrote to the treaty’s party nations asking them to exclude people with tobacco interests from their delegations.

In the latest note, the secretariat said it then turned to a FCTC leadership group for guidance after receiving a number of nominations from countries that ignored the suggestion.

(Additional reporting by Sue-Lin Wong in Beijing; Editing by Tom Lasseter, Robert Birsel)


Smoking-Linked Cancer Mutations Mapped

Scientists produce a detailed genomic map of mutations and epigenetic changes associated with smoking tobacco across 17 tumor types.

Researchers have uncovered the genomic mutations and DNA methylation patterns likely caused by tobacco smoke in 17 types of cancerous tumors. A comprehensive survey of mutations likely caused by carcinogens found in tobacco smoke by researchers at the Los Alamos National Laboratory in New Mexico, the Wellcome Trust Sanger Institute, and their colleagues was published today (November 3) in Science. The work provides a window into understanding the mechanisms by which tobacco smoke induces mutations that can lead to cancer in tissues that are directly or indirectly exposed to it.

“Comparing the mutations in cancers arising in smokers and non-smokers using genomic sequencing has never been done to this extent,” Gerd Pfeifer of the Van Andel Research Institute in Michigan, who was not involved in the work but penned an accompanying editorial, told The Scientist.

“This study highlights how important primary prevention remains for tobacco-related cancers and how much we still don’t know about the details of how tobacco causes cancer,” said Steve Rozen of the Duke-NUS Center for Computational Biology in Singapore who also was not involved in the study.

Ludmil Alexandrov of the Los Alamos National Lab, along with the Wellcome Trust’s Michael Stratton and their colleagues, used whole-genome sequences of 610 tumors and the exomes of 4,633 additional tumors, together covering 17 smoking-associated forms of cancer. The researchers examined each tumor as a mixture of multiple genomic mutation signatures identified in a previous study, which spanned a wider range of tumor types.?? Of the 5,243 tumors the researchers examined in the present study, 2,490 were derived from tobacco smokers and 1,063 from never-smokers.

“The hypothesis is that chemicals in tobacco directly damage DNA in tissues like the lung that are directly exposed to tobacco smoke. But there is not an understanding of how tobacco smoke increases the risk of cancer in other tissues not directly exposed to smoke like the bladder, and kidneys,” Alexandrov told The Scientist. “We wanted to understand the mechanisms by which tobacco can increase the risk for cancer.”

The tumor types with the highest odds ratio for developing cancer in individuals who smoke an average of more than 30 cigarettes a day are those that occur in tissues directly exposed to tobacco smoke, the researchers showed (small cell lung cancer, squamous lung cancer, and lung adenocarcinomas). Tallying the number of mutations observed in lung tissue samples, the researchers estimated that approximately 150 mutations accumulate in a given lung cell in individuals who smoke a pack of cigarettes a day for a year.

The team also found a mutational signature characteristic of tumors of the lung and larynx in smokers. This guanine-to-thymine base-pair change is thought to occur as a result of DNA adducts on guanines and has been previously demonstrated as the mutational signature that occurs in cells exposed to a known tobacco-derived carcinogen.

For tissues indirectly exposed to tobacco smoke, the picture is more complicated.

The researchers uncovered a complex mutational pattern spanning all the cancer types examined. This cellular aging–related mutational pattern was found in tumors from smokers and nonsmokers, but was enriched among smokers. “What we think is happening in this case is that tobacco smoke is deregulating a molecular clock, and that is increasing the speed with which these mutations accumulate,” explained Alexandrov. How these mutations occur is not yet clear.

“The tissues with direct tobacco exposure look different than tissues exposed indirectly,” said Rozen. “The ones affected indirectly are more mysterious, pointing out that we really don’t know the mechanism by which smoking causes tumors in these tissues.”

While different DNA methylation patterns in the blood cells of smokers compared to nonsmokers have been observed, in the present study, the researchers observed similar patterns of methylation in both groups.

Several tissues in which tobacco smoke–associated cancers develop are those involved in metabolism and waste filtration, such as stomach, liver, bladder, and kidney.

“These tissues don’t see the tobacco smoke directly, so the tobacco is likely acting through a proxy,” Alexandrov told The Scientist.

“We thought that this study would confirm prior results about smoking and cancer-causing DNA mutations,” he continued. “But we found quite a few new mechanisms suggesting that there is a lot that we still don’t know.”

Pfeifer suggested that the approach should now be used to study the origins of other cancers for which the carcinogen is unknown. “We can look at the mutational signatures to give us good clues on the type of mutagen that could have caused the mutations,” he said.

Alexandrov, Stratton, and colleagues now plan to apply the same methodology to uncover the mutational patterns and potential mechanisms behind other factors, such as obesity and hormonal changes, known to increase the risk of certain cancers. “We know that tobacco causes cancer and have revealed a suite of potential mechanisms. But there are a host of other factors that cause cancer and yet we have no idea about the mechanisms,” Alexandrov said.

L.B. Alexandrov et al., “Mutational signatures associated with tobacco smoking in human cancer,” Science, doi:10.1126/science.aag0299, 2016.