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Genetic and Environmental Influences in Colon Cancer

March 22, 2021
  • 00:00Support for Yale Cancer Answers
  • 00:02comes from AstraZeneca, dedicated
  • 00:05to advancing options and providing
  • 00:07hope for people living with cancer.
  • 00:10More information at astrazeneca-us.com.
  • 00:14Welcome to Yale Cancer Answers with
  • 00:17your host doctor Anees Chagpar.
  • 00:19Yale Cancer Answers features the
  • 00:21latest information on cancer care by
  • 00:23welcoming oncologists and specialists
  • 00:25who are on the forefront of the
  • 00:27battle to fight cancer. This week,
  • 00:29it's a conversation about genetic
  • 00:30and environmental influences in colon
  • 00:32cancer with Doctor Caroline Johnson.
  • 00:34Doctor Johnson is assistant professor
  • 00:36of Epidemiology in the Department of
  • 00:38Environmental Health Sciences at the
  • 00:40Yale School of Public Health and Doctor
  • 00:42Chagpar is a professor of surgical
  • 00:44oncology at the Yale School of Medicine.
  • 00:48Caroline you can
  • 00:50start off by telling us
  • 00:53a little bit about your research?
  • 00:56I use a technology called metabolomics
  • 00:58to investigate specific differences
  • 01:01in metabolism that affect colon cancer,
  • 01:04development progression and
  • 01:05even response to therapeutics.
  • 01:07So particularly in my research
  • 01:10I'm interested in examining
  • 01:13metabolism in patients that develop tumors
  • 01:15that occur on the right side of the colon,
  • 01:18so that is the area of the colon between
  • 01:21the appendix and slightly up from
  • 01:24there in the rectum and ascending colon,
  • 01:27because those patients have the poorest
  • 01:30survival and what we've seen in the
  • 01:33literature is actually female patients
  • 01:35have much higher incidence of tumors
  • 01:37that occur in this region of the colon,
  • 01:40so we've been using
  • 01:43metabolomics to get a
  • 01:45better understanding of the
  • 01:47metabolism of these tumors.
  • 01:48So maybe we can stop there
  • 01:50for a second and just kind of dig a
  • 01:53little bit deeper into what exactly
  • 01:55metabolomics is and how that works.
  • 02:00It's the study of all the small
  • 02:03molecules that are present within a
  • 02:05sample so we can take a biological sample
  • 02:08from a patient such as a blood sample,
  • 02:11or even a tumor tissue,
  • 02:14and we can analyze it in an agnostic manner.
  • 02:17So we examine basically all the different
  • 02:20levels of all the small molecules
  • 02:22that might be within that sample
  • 02:28and this is similar to genomics
  • 02:30or transcriptomics.
  • 02:30So small molecules are basically
  • 02:32metabolites that are within our
  • 02:34bodies that come from the processing
  • 02:36of things like dietary products,
  • 02:38and they produce vital components
  • 02:40that are needed for our bodies
  • 02:42for different biological processes,
  • 02:44such as growth and healing,
  • 02:46immune responses, energy,
  • 02:47and even sleep,
  • 02:49so metabolomic analysis can also
  • 02:52really show us about the metabolism
  • 02:54of an individual and it can
  • 02:56also show us metabolism of things
  • 02:58like environmental chemicals and
  • 03:00drugs as well within an individual
  • 03:03and that could
  • 03:05be produced by the bacteria or even
  • 03:07the microbiome within an individual.
  • 03:09And this technology is particularly
  • 03:12important for cancer
  • 03:13because we know that metabolites
  • 03:15can affect how a tumor grows as tumor
  • 03:17cells need nutrients and energy and the
  • 03:20tumors themselves produce metabolites.
  • 03:22So metabolomics can really provide
  • 03:24us great insight into how an
  • 03:26individual produces metabolites
  • 03:27and how this might propagate
  • 03:29tumor growth as well.
  • 03:31So basically you're
  • 03:32kind of looking at all of these
  • 03:34metabolites to gain some insight
  • 03:36into these colon cancers.
  • 03:38Tell us what sample you used to
  • 03:40to look at these metabolites.
  • 03:43One can imagine that there may
  • 03:45be many options that you would
  • 03:47have whether it's looking at the stool
  • 03:50or whether it's looking at tumor tissue,
  • 03:53or whether it's looking at blood.
  • 03:55So what exactly do you do to try
  • 03:58to gain this insight?
  • 04:00That's a really good question,
  • 04:03basically we can take anything, we can
  • 04:05take a blood sample or stool sample,
  • 04:08or a tumor tissue,
  • 04:09and we can obtain these from patients,
  • 04:12and we can extract all the different
  • 04:15metabolites out of these biological samples.
  • 04:18And what we end up with is sort of a mixture
  • 04:21of anywhere from maybe 3000 up to you
  • 04:24know 10 to 20,000 different molecules
  • 04:27that could be present within this
  • 04:31sample within my research so far,
  • 04:33we have primarily examined
  • 04:35tumor tissues from patients,
  • 04:37so with collaborations with
  • 04:39both Sloan Kettering Cancer Center
  • 04:42and also Yale Cancer Center,
  • 04:44we obtained over
  • 04:45200 tumor tissues from patients
  • 04:47where these tumors had been obtained
  • 04:50during surgery and we were able to
  • 04:53analyze these tissues to examine which
  • 04:56metabolites were present and how they
  • 04:58were different between different patients.
  • 05:01So how they were different between
  • 05:03both women and men and from patients
  • 05:06with right sided colorectal cancer
  • 05:08and also from tumors that occurred in
  • 05:11other regions of the colon as well?
  • 05:15And if all of these patients had cancer,
  • 05:18one would imagine that you're
  • 05:21really looking at the metabolomic
  • 05:23profile of tumors in these patients
  • 05:26is that different than what you
  • 05:29would expect in normal colon?
  • 05:31So are there some metabolites
  • 05:33that you would expect only in
  • 05:36tumors versus in healthy tissue?
  • 05:39Yeah, that's
  • 05:40a great question, so we know that
  • 05:44tumors have very sort of increased
  • 05:48rapid growth, so we tend to see metabolites
  • 05:52linked to energy metabolism and sort of
  • 05:56making those or encouraging those building
  • 05:59blocks to be built to build new cells so
  • 06:02we know there's a lot of what they call
  • 06:06metabolic rewiring that happens within
  • 06:08a tumor compared to a normal tissue.
  • 06:12Andwithin my research,
  • 06:14we were really interested in looking at the
  • 06:17tumors themselves and how they differed
  • 06:20between male and female patients because
  • 06:23what is quite interesting about
  • 06:25colorectal cancer and all cancers,
  • 06:27they tend to have a higher
  • 06:29incidence in male patients,
  • 06:30but what we see is that in
  • 06:32the right side of the colon,
  • 06:34women tend to have this higher incidence, so
  • 06:38we wanted to see what was different
  • 06:41metabolically about these tumors that
  • 06:43occur specifically in in women with right
  • 06:45sided colorectal cancer and what we saw
  • 06:48was that they had this very different
  • 06:50metabolic profile where they tended to
  • 06:53generate energy differently
  • 06:55and they use one metabolites where
  • 06:57they produce one metabolite school,
  • 06:59disparaging that seemed to be much
  • 07:02higher within this set of patients
  • 07:04than compared to male patients that had
  • 07:07right sided colon cancer,
  • 07:08and also patients that had tumors
  • 07:11in the other side of the colon.
  • 07:14So we've really gone after this
  • 07:16metabolic pathway to understand
  • 07:18more about this side of metabolism and
  • 07:21potentially how it could in the future
  • 07:24be potentially targeted for perhaps
  • 07:26a precision medicine approach for
  • 07:29these groups of patients.
  • 07:31That's interesting that
  • 07:33women have a metabolite that
  • 07:36processes energy differently than men.
  • 07:40I just wonder when I think about
  • 07:43Asparagine I started thinking about
  • 07:48nucleic acids and amino acids
  • 07:53that form the building blocks of
  • 07:57cells and whether these could be
  • 08:01manipulated based on dietary factors,
  • 08:05for example.
  • 08:07So when we think about how cells use energy,
  • 08:13sometimes that may be
  • 08:15mediated in part by people's dietary intake,
  • 08:19did you look at that as a
  • 08:22potential difference in male
  • 08:24versus female patients?
  • 08:26Within our cohort
  • 08:27we didn't have information on diet,
  • 08:30but that's very much something that
  • 08:32would be useful to have something
  • 08:35like a food frequency questionnaire,
  • 08:37which is sometimes collected
  • 08:39for different biobanks
  • 08:41and in different cohorts.
  • 08:43Yes, exactly I think it's
  • 08:47really important here,
  • 08:49but I think Asparagine does come from
  • 08:52many many different dietary sources
  • 08:54and it actually has been seen
  • 08:58to be produced potentially,
  • 09:01or metabolize by the microbiome as
  • 09:03well and it can be produced internally
  • 09:05through your own biochemical processing
  • 09:08of other metabolites through an
  • 09:10enzyme called Asparagine synthetase.
  • 09:12So, biologically,
  • 09:13it can come from your internal processing,
  • 09:16but it can also come from dietary sources,
  • 09:20and it can come from microbial
  • 09:22processing as well.
  • 09:24So, as with many metabolites that
  • 09:26are present within
  • 09:28tumors and also present within the colon,
  • 09:31we always have to take into account
  • 09:34all these different biological
  • 09:35sources of where they can come from.
  • 09:38So we can either
  • 09:40manipulate them and try and sort of,
  • 09:43potentially
  • 09:44reduce the effects of the disease,
  • 09:46or improve therapeutic response.
  • 09:48And it seems
  • 09:49to be so multifactorial when
  • 09:51you think about where all of
  • 09:53these metabolites can come from,
  • 09:55and all of the different processes
  • 09:58that could be going on
  • 10:00both within normal cells as
  • 10:02well as within cancer cells,
  • 10:05which raises the question,
  • 10:08do women normally have more of
  • 10:10this metabolite even outside
  • 10:12of their colon cancers?
  • 10:15I think in this context what we've begun to see
  • 10:19is that Asparagine might be increased in
  • 10:22these patients because these tumors may be
  • 10:25what we call nutrient deplete and this is
  • 10:27something that we still have to look into,
  • 10:30so we can't really confirm this,
  • 10:32but just from our metabolomic studies,
  • 10:34it seems to be indicating this.
  • 10:36And this is maybe due to differences
  • 10:39in blood supply to the tumor,
  • 10:41or something else.
  • 10:42Less oxygen
  • 10:44that might be getting to the tumor.
  • 10:46And when we look at the other
  • 10:49processes that are going on
  • 10:51within these samples we see
  • 10:53that the generation of other energy
  • 10:56metabolites is different as well,
  • 10:58which could be indicating that
  • 11:00there could be something particular
  • 11:03about how these tumors might be
  • 11:05growing in this area of the colon.
  • 11:07So at the moment we don't have normal
  • 11:10colon tissues from from individuals,
  • 11:12but that's something that we do want
  • 11:15to look at to see if
  • 11:19the patients that do not have
  • 11:21colon cancer, if the colon tissues have these
  • 11:25different metabolites that
  • 11:27could be different between men and women,
  • 11:33and could affect the development of these tumors.
  • 11:35You kind of wonder as
  • 11:39well whether this is cause or effect.
  • 11:42So in other words, is it that you
  • 11:45had a tumor which was growing,
  • 11:48which then caused this
  • 11:50altered metabolomic profile,
  • 11:52or was it that you had some other
  • 11:54processes that were going on that
  • 11:57altered your metabolomic profile,
  • 11:59which then spurred on the cancer?
  • 12:01Did you gain any insight into that question?
  • 12:06I think it's probably more of the latter.
  • 12:10We see that Asparagine
  • 12:14is produced internally.
  • 12:16As I mentioned through this
  • 12:18enzyme asparagine synthetase,
  • 12:20and this enzyme is controlled somewhat by
  • 12:23another gene mutation of aging mutant Kras,
  • 12:27so it could be that these tumors
  • 12:32have this oncogene and it could
  • 12:34be affecting these metabolites,
  • 12:36so it could be an effect that we're seeing,
  • 12:39but it is probably a combination
  • 12:42of many things, that includes this
  • 12:44potential mutation to this gene.
  • 12:46But also it could be the way
  • 12:48that the tumor is growing
  • 12:50as I mentioned within the
  • 12:52colon as well and all together,
  • 12:54all these different processes are
  • 12:56causing this effect of this increase
  • 12:59in Asparagine that seem to help
  • 13:02propagate the tumor when it
  • 13:04might be under these stress
  • 13:06conditions where it's not able to obtain
  • 13:08nutrients in a normal fashion,
  • 13:10so I think this is what
  • 13:13could be happening.
  • 13:14And also as I mentioned as well,
  • 13:17this combination of the microbiome
  • 13:19present as well within the colon
  • 13:22that could be affecting how this
  • 13:24metabolite is being processed.
  • 13:29And it's an interesting puzzle to
  • 13:31think about how metabolomics works
  • 13:33along with genetic mutations and so on
  • 13:36when we think about colon cancer.
  • 13:39We're going to take a short
  • 13:41break for a medical minute.
  • 13:43Please stay tuned to learn more
  • 13:45about genetic and environmental
  • 13:47influences in colon cancer with
  • 13:49my guest Doctor Caroline Johnson.
  • 13:51Support for Yale Cancer Answers
  • 13:53comes from AstraZeneca, working to
  • 13:56eliminate cancer as a cause of death.
  • 13:58Learn more at astrazeneca-us.com.
  • 14:02This is a medical minute
  • 14:03about head and neck cancers,
  • 14:05although the percentage of oral in
  • 14:07head and neck cancer patients in
  • 14:10the United States is only about
  • 14:125% of all diagnosed cancers,
  • 14:14there are challenging side effects
  • 14:16associated with these types
  • 14:17of cancer and their treatment.
  • 14:19Clinical trials are currently
  • 14:20underway to test innovative new
  • 14:22treatments for head and neck cancers,
  • 14:24and in many cases less radical
  • 14:26surgeries are able to preserve nerves,
  • 14:29arteries and muscles in the neck,
  • 14:31enabling patients to move,
  • 14:32speak, breathe and eat normally
  • 14:35after surgery.
  • 14:36More information is available
  • 14:38at yalecancercenter.org.
  • 14:39You're listening to Connecticut Public Radio.
  • 14:43Welcome back to Yale cancer answers.
  • 14:46This is doctor Anees Chagpar and I'm
  • 14:48joined tonight by my guest doctor
  • 14:50Caroline Johnson and we're talking about
  • 14:52genetic and environmental influences in
  • 14:55colon cancer and right before the break,
  • 14:57Caroline was telling us about her
  • 14:59studies looking at metabolomics.
  • 15:01That is to say the study
  • 15:04of different metabolites.
  • 15:05Looking at gender differences
  • 15:06in right sided colon cancer.
  • 15:08So Caroline, I wanted to dig into
  • 15:11that a little bit more because we
  • 15:14started to talk about whether
  • 15:16these metabolomic changes
  • 15:19are what drives the colon cancer or
  • 15:22whether the colon cancer is what
  • 15:24drives the metabolomic changes,
  • 15:27and you had mentioned that the
  • 15:30metabolomic changes may be in part
  • 15:33related to mutations in KRas,
  • 15:36but we know that Kras and oncogenes
  • 15:40may spur on cancers as well.
  • 15:43I wonder whether these two processes
  • 15:46are independent of each other.
  • 15:49That is to say,
  • 15:50Kras causes metabolomic changes and
  • 15:53also causes separately tumor development
  • 15:55or whether these are Interrelated.
  • 15:59Do you have any sense on that?
  • 16:03I think they are interrelated and the
  • 16:07findings that we have seen
  • 16:10linking Mutant Kras and Asparagine
  • 16:12have been seen in other cancers as well.
  • 16:16So you know the mutant carriers is very
  • 16:19common in pancreatic cancers and there is a
  • 16:22clinical trial right now
  • 16:25actually that I saw yesterday
  • 16:27for targeting Asparagine by
  • 16:29using a drug
  • 16:31along with other first line chemo.
  • 16:36So we do know that the mutant
  • 16:39Kras does regulate other
  • 16:41genes and signaling pathways that
  • 16:43does affect Asparagine production.
  • 16:45So I think it's probably a case of mutant
  • 16:48Kras affecting Asparagine levels.
  • 16:51But of course, as I mentioned before,
  • 16:53asparagine can be modulated by other sources,
  • 16:59and also from the microbiome,
  • 17:02and we have analyzed the microbiome from some
  • 17:05of the tumors from the right sided patients.
  • 17:09So from both men and women,
  • 17:12and we have a sense that
  • 17:14there is some microbiota
  • 17:17that are correlated with asparagine
  • 17:19levels only in in the female patients.
  • 17:22So we do believe there is a
  • 17:26multifactorial effect
  • 17:27on asparagine production
  • 17:28that could be itself propagating
  • 17:31the tumors as well by giving
  • 17:34them more nutrients,
  • 17:35we know that Asparagine can increase
  • 17:38the uptake of other amino acids and can
  • 17:41affect other processes such as even
  • 17:44polymetabolite
  • 17:46production or autophagy,
  • 17:47another process is like that.
  • 17:49So I believe this is
  • 17:52very wide combined effect.
  • 17:54And really the technology metabolomics
  • 17:57has allowed us to get an insight into
  • 18:00this because we can not only
  • 18:03analyze Asparagine,
  • 18:04we can analyze all the other
  • 18:07metabolites that could be
  • 18:08affected by asparagine levels as well,
  • 18:10it could be affected by mutant Kras
  • 18:13so it really is
  • 18:14a wider scope or a magnifying
  • 18:18glass really into looking more into
  • 18:21how these pathways are regulated
  • 18:23by both genes and metabolites.
  • 18:26Have you found a difference in
  • 18:28Asparagine between men and
  • 18:31women who are Kras negative?
  • 18:32That is to say, they don't
  • 18:35have a Kras mutation.
  • 18:37I wonder whether
  • 18:40these two are directly linked,
  • 18:42so for example,
  • 18:43women may have more Kras mutations,
  • 18:47and therefore you may be seeing
  • 18:49these metabolomic differences
  • 18:50or whether these are really
  • 18:53separate processes altogether?
  • 18:56We haven't looked at that specifically
  • 19:05but what we have done is we've
  • 19:08looked at survival, and actually
  • 19:10there's many different
  • 19:12publicly available data sources
  • 19:14that we can look at to look at gene
  • 19:17expression and also patient survival.
  • 19:19So we looked at mutant Kras
  • 19:21we looked at asparagine synthetase
  • 19:24and we saw that patients with these
  • 19:27genes had much poorer survival if
  • 19:30they were female and they had a right sided
  • 19:34tumor so we compared,
  • 19:36the Kras mutant to the Kras
  • 19:38wild type, and it was again
  • 19:39in these different resources
  • 19:41we saw that it was always the female
  • 19:43patients of right sided colon
  • 19:45cancer that had the poorer survival,
  • 19:47and we looked at asparagine
  • 19:48levels within our own cohorts.
  • 19:50And we looked at the survival data because
  • 19:52our tumors were collected in the 1990s,
  • 19:54so we were able to follow up
  • 19:56with survival of the patients.
  • 19:58And we saw that it was again,
  • 20:00the women with
  • 20:01right sided tumors
  • 20:03that had poor survival,
  • 20:05and increased risk of recurrence if
  • 20:07they had high asparagine levels.
  • 20:11Interesting and did you
  • 20:13look at whether these asparagine
  • 20:15levels were higher in tumors that
  • 20:17were larger versus smaller, or was it
  • 20:20if you looked at two tumors
  • 20:22that were identical in terms
  • 20:24of their size and their grade,
  • 20:26and the level of invasion
  • 20:28and their lymph node status,
  • 20:30and all of the other markers
  • 20:32that we look at for prognosis
  • 20:34was asparagine independently
  • 20:36associated with prognosis?
  • 20:37We didn't have the size of the tumors
  • 20:40to sort of understand that,
  • 20:42but that's a very good question.
  • 20:44What we did was we we had a very small
  • 20:47amount of tumor from each patient,
  • 20:49but it was the same size for each
  • 20:52patient that the biopsy that we had.
  • 20:54So we compared between those biopsy sizes.
  • 20:57But we did take into account things like
  • 20:59the stage of the patient and we saw
  • 21:02across the board that it was stage one,
  • 21:05stage two and three that had
  • 21:07high levels of asparagine in the
  • 21:10women with right sided colon cancer,
  • 21:13but for men they didn't have
  • 21:15these high levels of asparagine
  • 21:17at these different stages,
  • 21:19so it tended to be mostly in the
  • 21:22women again.
  • 21:24And so when you looked at prognosis,
  • 21:26did you look at it and found that
  • 21:29asparagine was correlated with prognosis?
  • 21:31Was that independent of
  • 21:32their stage at presentation?
  • 21:35Yes, it seems to be
  • 21:39independent of stages
  • 21:41asparagine levels within the tumors.
  • 21:43So what we really want to do
  • 21:45next is we want to obtain blood
  • 21:47samples from patients to see if
  • 21:49we can measure asparagine levels.
  • 21:52And if this could be potentially a
  • 21:54biomarker as well for these patients.
  • 21:56So that's something that we want
  • 21:58to validate in a larger cohort.
  • 22:00That's something we're looking into
  • 22:02right now to collect these samples.
  • 22:05When we were talking about cause
  • 22:07versus effect, it really gets to
  • 22:10your next steps, right?
  • 22:12So if we think that
  • 22:15asparagine is really an effect,
  • 22:17in other words, you have a tumor that
  • 22:20then causes asparagine levels to go up,
  • 22:23such that those asparagine levels
  • 22:26are predictive of prognosis,
  • 22:27certainly thinking about,
  • 22:29can we use this as a biomarker,
  • 22:32especially if it can be found in something
  • 22:36simple like a blood sample or a stool sample,
  • 22:40might be helpful.
  • 22:41On the other hand,
  • 22:43if we think about it being more of a cause,
  • 22:47that is to say,
  • 22:48if you have high levels of asparagine that
  • 22:52then sets off a cascade that leads
  • 22:55to worse tumors and worse prognosis,
  • 22:58then the concept might shift
  • 23:00not only to be a biomarker,
  • 23:03but to really think about
  • 23:05this as a therapeutic target.
  • 23:07So where where do you kind of come down on
  • 23:11your next steps with regards to that?
  • 23:15That's a really good question.
  • 23:17We are currently designing
  • 23:19studies to look at the effect of
  • 23:22asparagine on tumor growth.
  • 23:26Providing a different cell line,
  • 23:28and animal models asparagine to see
  • 23:30if it does propagate tumor growth.
  • 23:33There was a study
  • 23:36out in Nature a couple of
  • 23:38years ago where they in a different
  • 23:41cancer model, in a breast cancer model,
  • 23:44they fed mice
  • 23:45asparagine in their diet and
  • 23:47they saw that it actually caused
  • 23:49the primary tumor to metastasize.
  • 23:51So there's been a number of studies
  • 23:54that have looked into asparagine and
  • 23:56have seen that it can propagate tumor growth.
  • 23:59So we had we have a study that has been
  • 24:03funded by the American Cancer Society
  • 24:05where we will be looking at the effect
  • 24:08of both the gene that produces
  • 24:11asparagine so asparagine synthetase,
  • 24:13and we've developed some cell lines where
  • 24:15we have the knockout of this gene,
  • 24:18and we will be
  • 24:22injecting this
  • 24:25into mice and also to feed them
  • 24:28asparagine to see if it will actually
  • 24:32affect tumor growth so
  • 24:35hopefully in the future
  • 24:37down the line we can sort of test
  • 24:40to see if any of the asparagine
  • 24:42reducing drugs
  • 24:45could be used as a therapeutic
  • 24:47to reduce asparagine levels
  • 24:49in colon cancer patients, potentially.
  • 24:52iI's so interesting when you talk about that
  • 24:55study in breast cancer where feeding
  • 24:57asparagine led to increased metastasis.
  • 25:00One of the obvious questions I'm sure
  • 25:02all of our listeners want to know is
  • 25:06what foods out there are high in asparagine?
  • 25:11That's something
  • 25:13we're looking into as well.
  • 25:15As with any sort of food source,
  • 25:18there are many different components
  • 25:19within a
  • 25:21vegetable or within
  • 25:24anything that you eat.
  • 25:29I think if it was going to be given
  • 25:33as a therapeutic
  • 25:36I don't know if diet is
  • 25:39really the best way to approach it.
  • 25:42It could be better to potentially
  • 25:44try and reduce
  • 25:45asparagine levels,
  • 25:46and that's what I mean as using
  • 25:49it as a preventative measure
  • 25:52so encouraging people to eat less
  • 25:54foods that are high in asparagine.
  • 25:57Which brings us to the
  • 25:58question which foods are those?
  • 26:04At the moment we don't really know
  • 26:06which foods have high asparagine levels.
  • 26:09That's something that we
  • 26:11would need to look into 'cause you know
  • 26:13each food product does contain many
  • 26:16different amino acids and other products,
  • 26:18and it tends to be some food products that
  • 26:21may have higher asparagine levels have
  • 26:23other beneficial properties.
  • 26:28Yeah, that's a
  • 26:30really interesting point,
  • 26:31but I think that perhaps
  • 26:33targeting maybe
  • 26:36a therapeutic standpoint from
  • 26:38using something like asparagine.
  • 26:40AIDS might perhaps be more effective,
  • 26:43but definitely the diet would be
  • 26:45something that would be useful
  • 26:48to look into for these patients.
  • 26:50Yeah, because they kind of wonder
  • 26:53whether women just naturally
  • 26:55gravitate towards eating foods
  • 26:57that are higher in asparagine
  • 26:59or whether they process those
  • 27:03differently such that they end up with
  • 27:06higher levels of asparagine versus men,
  • 27:09and so understanding how
  • 27:12they metabolize those foods
  • 27:15might play a role, but can you
  • 27:18comment that in looking at the
  • 27:21enzymes that breakdown asparagine and
  • 27:24also those that increase asparagine ,
  • 27:27did you find a difference between men and
  • 27:30women in terms of their natural enzymes?
  • 27:33Even outside of the cancer patient?
  • 27:36We haven't looked at
  • 27:37the expression levels of those,
  • 27:40but that's a really interesting point.
  • 27:43We do know that the asparagine synthetase
  • 27:46is associated with poor survival
  • 27:48if it's a higher expression only in
  • 27:51women with right sided colorectal cancer.
  • 27:53But I think also having a
  • 27:56look more deeply at the microbiome
  • 27:58because we know that there are many
  • 28:01species within the microbiome that
  • 28:03can also metabolize asparagine.
  • 28:05This could be, you know,
  • 28:07another therapeutic that
  • 28:09could be explored as well,
  • 28:11and I think having a
  • 28:13more in depth look at
  • 28:16the microbiome that could be
  • 28:18present within the stool sample or
  • 28:20within the tissue samples within
  • 28:22patients is also really important.
  • 28:25The other question
  • 28:27that comes to mind is while your
  • 28:30research is really focused on the
  • 28:32differences between men and women,
  • 28:34one wonders, especially when you
  • 28:36think about the potential role for
  • 28:39asparagine in mediating prognosis.
  • 28:41I'm going back to that study
  • 28:44that you said was published in Nature
  • 28:47in the breast cancer model,
  • 28:49whether if you look at
  • 28:52men with colon cancers,
  • 28:53whether men with higher levels
  • 28:55of asparagine do worse than men
  • 28:57with lower levels of asparagine
  • 28:59have you looked at that?
  • 29:00We have and it doesn't
  • 29:02seem to be the case,
  • 29:04so it seems to be sort of what we've
  • 29:07seen is the opposite way round.
  • 29:10The with you for male patient
  • 29:12has higher levels of disparaging.
  • 29:14They tend to do better.
  • 29:16So it's really perplexing
  • 29:18Interesting, you know,
  • 29:19and it's really fascinating,
  • 29:20so it's something that you know
  • 29:22where we're looking into within
  • 29:23my lab in different models,
  • 29:25so hopefully we'll get
  • 29:27better insight into this in the
  • 29:29the next couple of years or so.
  • 29:31Doctor Caroline Johnson is assistant
  • 29:33professor of Epidemiology in the Department
  • 29:36of Environmental Health Sciences at
  • 29:37the Yale School of Public Health.
  • 29:40If you have questions,
  • 29:41the address is canceranswers@yale.edu
  • 29:43and past editions of the program
  • 29:45are available in audio and written
  • 29:47form at yalecancercenter.org.
  • 29:48We hope you'll join us next week to
  • 29:51learn more about the fight against
  • 29:54cancer here on Connecticut Public Radio.