New Considerations in Defending Against Lung Cancer Cases Part 2: Genetic Signatures

Lung cancer claiming in asbestos litigation is not gone. To the contrary, a very recent report from KCIC points out the numbers, including 60 lung cancer filings this year by Napoli Shkolnick, 54 cases by Weitz & Luxenberg, and 35 by the Simmons firm.

More broadly, KCIC explained:

Lung cancer filings make up about 24 percent of the total filings received this year through August 31. Of these cases, Gori Julian & Associates filed the most cases at 120 and Napoli Shkolnik is second with 62. Again, Madison County, IL, is the jurisdiction with the highest number of filings, but the percentage of total lung cancer filings is much lower than that of mesothelioma. Madison County, IL, has seen 102 lung cancer filings according to our data and the number two jurisdiction — again St. Louis, MO — has seen 94 lung cancer filings to date.

In view of the falling numbers of smokers, and the notable numbers of lung cancer case filings over the past five years, lung cancer cases require serious attention by defense counsel. We believe it is highly likely that molecular issues will play a more prominent role in lung cancer cases moving forward. By presenting credible experts, and staying on top of the relevant genomic science, attorneys can be prepared to present the best arguments, and can diminish the chances of suffering through being ambushed by the other side.

As we have discussed previously [see here, here, and here], the ongoing revolution in molecular science has led to dramatic increases in our understanding of the human genome, including how environmental agents may impact the genome (e.g. DNA mutations, epigenetic changes, alterations in microRNA expression, etc.). In addition, plummeting costs of genetic-sequencing and related technologies have made it possible to take a close look at the DNA sequence of an individual in order to assess the presence or absence of genetic mutations or other genomic alterations that can address the questions of predisposition, or assigning attribution to a particular exposure (e.g. ionizing radiation, tobacco smoking, asbestos, etc.). In other words, these molecular techniques are potentially useful tools for investigating potential attribution to genetic causes and other potential environmental agents in cases of lung cancer, and may allow for the attribution of disease causation at the individual level, depending on what judges and juries decide about evidence and legal issues.

It is also important to remind our audience that genomic science should not be considered brand new and emerging science. It is widely used in medicine for a variety of purposes, such as predicting a patient’s response to a drug. In addition, genetic analyses have been used in many legal cases, with genetic evidence admitted and considered by the jury as to paternity or whether an individual’s DNA was left at a crime scene.

In the following sections we described new scientific developments in genetic signatures related to the causal pathway of lung cancer in asbestos litigation. Given the significant increase in asbestos-related lung cancer case filings over the past five years, it is highly likely that molecular issues will play a more prominent role in lung cancer cases moving forward. By staying on top of the relevant genomic science, asbestos defense attorneys can be prepared to mount the best defense possible, as well as diminish the chances that you will be ambushed by your opponents.

New Molecular Signatures in Lung Cancer

In recent years, scientists have raised new issues for asbestos litigation by seeking to identify molecular signatures or genetic patterns that could provide a biological explanation for lung cancers to counter the view that low levels of asbestos exposure were causally associated with the development of the tumor. At a very high level, this could distinguish a lung cancer which is related to asbestos exposure relative to one that is not. For instance, a particular lung tumor may have a fingerprint that is consistent with tobacco smoke, radiation, etc. and not with a fingerprint that is associated with asbestos. On this note, a recent study provides data that can be used by defendants to define lifetime tobacco smoke exposure from epigenetic profiles (i.e., assess whether a plaintiff really stopped smoking when they said they did).

The search for unique genomic fingerprints in cells making up the tumor (in scientific terms, this is can be referred to as somatic mutation signatures) is made possible by comparing the similarities and differences of tumors relative to their organ/tissue of origin. By comparing DNA derived from the tumor to DNA from normal tissue (e.g. comparing lung tumor to normal lung), genomic differences and their potential significance can be assessed. As alluded to earlier, advances in molecular science have made it possible to begin grouping together cancers based on unique genetic signatures, and subsequently determining commonalities among these groups of cancers, largely based on data collected from the patients (e.g. occupational history, smoking status, etc.). For instance, one may find that there exists a subset of lung cancers with a certain genetic signature, and these cancers happen to associate strongly with patients that were exposed to ionizing radiation, or tobacco smoke, or asbestos, etc. It is expected that the volume of data related to cancer and genetic alterations will increase substantially over the next few years. Below we describe two programs that will certainly contribute to this emerging body of data.

One project known as COMSIC (Causes of Mutational Signatures) is seeking to gain a broad understanding of the potential effects of toxic chemicals on the genome. A recent publication by this group detailed their findings from conducting whole genome sequencing of mouse cells following exposure to various mutagens. Overall, the different mutagens were shown to produce unique mutation signatures (Nik-Zainal, 2015). These types of data point to the view that certain exposures will leave their mark on the DNA, and researchers have been publishing data on such fingerprints related to a variety of exposures, including asbestos, as described below.

A recent study published by a Finnish research group reported their results related to genetic sequencing that was conducted to determine the association of known mutations with asbestos. The goal was to identify new mutations related to asbestos exposure in lung cancer and mesothelioma. Overall, in asbestos-exposed mesothelioma patients, new (previously non-described) and expected mutations were detected. Interestingly, additional analyses pointed to additional genes potentially associated with asbestos exposure (Maki-Nevala, 2016).

Further, earlier this year an article published in the New England Journal of Medicine highlighted the importance of paying close attention to the unique molecular alterations in the histological subtypes of lung cancer (Swanton, 2016). In particular, the unique molecular signatures serve as a rich source of information related to potential susceptibility genes, and a basis for understanding how certain toxic exposures may change these signatures. Overall, defense attorneys should be asking questions related to lung cancer subtypes, as well as the underlying genomics of the tumor. These types of analyses may help establish potential alternative cause arguments.

As molecular technologies continue to develop and data continues to emerge, our understanding of lung cancer signatures and their relationship to toxic exposures will become more refined. Ultimately, depending on how judges and juries view the scientific evidence, there may come to be unique lung cancer signatures that may implicate a certain exposure with a particular lung cancer, or help exonerate defendants.

How Are You Monitoring the Science?

Are you struggling to maintain an up-to-date awareness of the science related to your cases? We’ve designed a tool to help busy litigators and litigation teams stay current on the science – we call it DataTrove®. Click here to learn more about our unique tool.

Giovanni Ciavarra, Ph.D.

Kirk Hartley, Esq.