what about cancer? Again, nobody wants cancer. Uh, we've all known people who've died of cancer, um, or have had cancer. What can be done to reduce one's risk of cancer? Well, you asked earlier about the numbers. So let's throw some numbers out there, right? So globally we're talking about 11, 12 million deaths per year, about half the number of ASCVD, still a staggering number.

Um, at the individual level, put it this way, somewhere between one in three and one in four chance, anyone listening to this or watching this is going to get cancer in their lifetime. But what's the probability they will die from that cancer? Half of that, about a one in six chance of dying.

Okay. So is it true that every male gets prostate cancer? Most, in other words, on their deathbed, many men will die with prostate cancer and some will die from it. You and I have prostate cancer right now. Thank you for informing. Yes. Hopefully we will not die of it.

We should not die of it. Prostate cancer, colon cancer are cancers that no one should ever die from because they're so easy to screen for. They are so easy to treat when they are in their infancy, um, that it's totally unacceptable that people are dying from this. There are other cancers for which I can't really say that.

Breast cancer, much more complicated. Pancreatic cancer, much more complicated. Glioblastomae multiforme, much more complicated. So there, you know, as you said a second ago, cancer is not a disease. It is a category of diseases. Each, it's not just that each organ is different and breast differs from pancreatic. It's that within breast cancer, ER, PR positive, HER2/neu positive is a totally different disease from the triple negative breast cancers.

Those with BRCA mutations or non-BRCA mutations. Oh, yeah. Even putting that aside, just looking at the hormone profile of the individual breast cancers, they're totally different diseases. So it's not just that breast cancer is different from prostate cancer. It's that all breast cancers are quite different. Maybe I should frame the question a little differently than given the vast number of different types of cancers and categories within those.

Your question is still a fair one. I just wanted to throw that caveat out there. So now to your question. Okay. So what do we know? It turns out that we can very comfortably speak to several things. One is the role that genes play. So maybe I'll just spend one second on a gene 101 thing for the viewer.

We want to differentiate between what are called germline mutations and somatic mutations. So your germline and my germline are set. When we were born, our germline mutations... Any mutations we have in germline genes are inherited from our parents. They're non-negotiable. They're non-negotiable. You got those things. So question one is how much of cancer results from those types of genetic mutations?

And the answer is very little, less than 5%. So very... You mentioned one a moment ago, BRCA. Okay. So mutations in BRCA are germline mutations. A woman will get a BRCA mutation from one of her parents. And we will often have a sense of that just from the family history.

When mom and sister and aunt and grandmother had breast cancer, you've got a breast cancer gene. Now it might be BRCA. It might be another gene that's not BRCA, but there's no ambiguity. And we test for these genes mostly just for insurance purposes, frankly, but there's no ambiguity that that was a germline transmission of a gene that is driving cancer.

But 95+% of cancers are not arising from germline mutations. They are arising from somatic mutations or acquired mutations. So the question then becomes what is driving somatic mutation? And the two clearest indications of drivers of somatic mutation are smoking and obesity. Smoking we've talked about. Let's put that aside for a moment.

I'm so surprised about obesity. I don't know why I'm surprised, but I've never heard this. I'm probably just naive to the literature. Yeah. So obesity is now the second most prevalent environmental driver of cancer. Now I will argue, and I think I argue this in the book, hopefully pretty convincingly, I don't think it's obesity per se.

I think obesity is just a masquerading proxy. What is obesity? Obesity simply is defined by body mass index. Well, first of all, I don't think I'm obese, but I'm way overweight on BMI. You probably are too. So, you know, let's just ignore that. I'm clinically diagnosable as obese. Are you?

Oh, no. Well, not clinically. That would be BMI over 30. I don't think you're probably there. No, but if I measure my weight by height... Yeah, yeah, yeah. My BMI is probably 27 or 28. Okay. It's been a little while since I've checked. I only know body fat percentages and things like that.

So basically, like BMI is a far from perfect proxy, but at the population level, it's what we use. I wish we would get off it, by the way. I think it's really crap. Because it doesn't take into account lean versus non-lean tissue. Yeah. I think we could get better data if we looked at waist to height ratio.

That's a way better metric. So this is just a quick test for everybody. I'm going to argue your BMI is less relevant to me than your eye color. But if your waist circumference is more than 50% of your height, you should be concerned. Okay. Well, then I'm okay. Yeah, you're fine by that metric, right?

But that's important. So if you're six feet tall, your waist better be under 36 inches. And if it's over, I would argue that's the definition of obesity, not your BMI being over 30. So back to this issue, because we're using such a crude measurement, it basically is catching a whole bunch of stuff.

But the question is, what's driving it? And I think if you really look at the physiology of cancer, I don't think it's obesity. I think it's two things that come with obesity, insulin resistance, which is two-thirds to three-quarters of obese individuals are insulin resistant, and inflammation. And I think those two things, with the inflammation and the immune dysfunction, with the insulin resistance and the hyper basically tonic growth stimulus that's coming, that's what's driving cancer.

So again, is it because a person is storing extra fat and their love handles that that's driving the risk of cancer? No. Those are just two things that are coming along for the ride. So beyond those two things, and along with certain... There are also certain environmental toxins we absolutely know are doing this, right?

So we understand that people who have exposure to asbestos have a much higher risk of certain types of lung cancers and things like that. But for the most part, those are our big risks. Beyond that, we talk about alcohol in certain cases, absolutely. Alcohol is a carcinogen. The dose part still isn't clear to me.

I don't know, is one drink a day moving the needle much on cancer risk per se? It's not clear. And it might depend on those genetic predispositions. So, yeah, if step one is don't get cancer, you have no control over your genes, you have control over smoking, you have control over insulin sensitivity.

I wish I could sit here and tell you that there is a proven anti-cancer diet, or that if you do X amount of exercise per week, you're going to not get cancer. We just don't have a fraction of the control over cancer that we have with cardiovascular disease. We don't understand the disease well enough.

So we don't understand kind of the initiation process and the propagation process. And we have to rely much more on screening. Are there good whole body screens for cancer? In other words, can I walk into a tube and or a cylinder rather, and get screened for the presence of tumors any and everywhere in the body outside the brain?

Because the brain is a little harder to get to, right? Believe it or not, the brain is actually pretty easy to screen for. Because it's so fatty and floating in water. Well, and also the head, when you put the head into an MRI scanner, there's no movement. It's the least motion artifact is in the brain.

So when you use something called diffusion weighted imaging with background subtraction in an MRI, a technology that was actually pioneered in the brain for stroke identification, it's also really good at looking for tumors as well. So let me make the argument for why screening matters. Because this is, again, kind of an area where I go far down a rabbit hole in a way that I think traditional medicine would argue against.

So my argument for screening is an argument at the individual level. And it goes as follows. To my knowledge, there is not a single example of a cancer that is more effectively treated when the burden of cancer cells in the body is higher than when it is lower. So the two examples I think I talk about in the book are colon cancer and breast cancer.

So when you take an individual with stage four colon cancer, that means that the cancer has left the colon and is now outside of the colon. So it's usually in the liver at a minimum, potentially in the lungs or in the brain. That person's five-year survival is very low.

Their 10-year survival is zero. We will treat them with a very aggressive regimen of multiple drugs. And again, you'll get a five-year survival of maybe 10% to 20%. And by 10 years, nobody's alive. If you take a person with stage three colon cancer, so the colon cancer is big and it's even in the lymph nodes around the colon.

But at least grossly, you can't see those cells in the liver. Microscopically, of course, we know they're there. Because if you don't treat those patients, they still die of colon cancer. But you whack them with the same chemo regimen that you were going to give the metastatic patients, 80% of those people are alive in five years.

So night and day difference in survival. What's the difference? In the person with metastatic cancer, you're treating a person with hundreds of billions of cells. In the adjuvant setting, which is what we call it adjuvant when you treat people who have only microscopic disease, you're treating billions of cells.

The same is true with breast cancer. So we have the clinical trial data to put them side by side. So rule number one is don't get cancer. Rule number two is catch cancer as early as possible if you're going to get it. Which brings us to your question of how do you screen for it?

We basically screen, the first line of screening is imaging, is a sort of visualization. So you have cancers that occur outside the body that you can look at directly. So skin cancer, you can look directly at the skin. Esophageal, gastric, colon cancer, those are outside the body, right? Mouth to anus embryologically is outside the body.

So you can put a scope in and you can look directly at the cancer. But for all other cancers that are inside the body, yeah, you have to rely on some sort of imaging modality. Although now we're starting to look at things called liquid biopsies. So blood tests that are looking for cell-free DNA.

And the cell-free DNA gives us a sense of based on the epigenetic signature of what you're looking at, hey, is there a cancer in the body? And if so, what tissue is it potentially coming from based on these epigenetic signatures? So the problem with relying on any one modality is a problem of sensitivity and specificity optimization.

Now with MRI scanners, which are in some ways the best way to do this because they don't have radiation. So you don't want to be incurring damage as you do this. The irony of doing a whole body CT scan to screen for cancer is your whole body CT scan would be close to 30 to 50 millisieverts of radiation.

It's a staggering sum of radiation. So does that mean that people should, sorry to pull you off this, but I was going to ask about this anyway, avoiding going through the whole body scanner at the airport? Noise. So low. So low. Yeah. Going through a whole body scanner at the airport or even getting a DEXA scan.

I mean, these are trivial amounts of radiation. What about flying? You hear that pilots get more cancer. If you're a pilot who's flying over the North Pole back and forth and back and forth, you're probably getting, you know, five to 10 millisieverts a year. The NRC suggests that nobody should get more than 50 millisieverts a year.

So you and I both travel a fair amount, but typical travel for the busy person, let's say two round trip flights of more than two hours per month and an international trip every three months. Probably still less than a millisievert a year. Yeah. Living at sea level, one millisievert a year, living at a mile elevation.

If you lived in Denver, you're at two millisieverts a year. I have to ask standing in front of the microwave. I'm just, we've got friends. They ask. With or without testes on the counter. That's an inside joke that unfortunately and fortunately deserves no description. And Peter's not referring to me.

But people worry about other sources of radiation. So it doesn't sound like the microwave is a concern. What are the other major sources of radiation? I mean, outside of sort of nuclear stuff where things go sadly wrong. You live near a plant or there's been a... Yeah, there's been a...

It's mostly at the hands of medical professionals, right? It's the CT scanner and the PET scanner are hands down the biggest source of radiation. What about the x-rays at the dentist when they go... They're very low. When they scurry behind the wall, put me under the blanket. They're very low, relatively speaking.

Fluoroscopy is very high. They tend to try to cover up all of you that... So for example, if they were doing a fluoroscopic study of your kidney because you had a stone or if you were getting an injection into, you know, if they were doing a fluoroscopic guided injection of one of your discs in your neck, that would be a locally pretty high dose.

But they're going to cover the hell out of you elsewhere. And again, if you get one of these things, it's not the end of the world. But boy, I wouldn't want to be getting one a month. And back to the point about screening, you know, a chest abdomen pelvis CT scan is probably...

I mean, look, there's probably a scanner out there now that's moving fast enough that it's much lower. But I'll give you an example. Okay. Remember how I talked about we do CT angiograms on all of our patients for coronary artery disease? An off-the-shelf scanner for this is 20 millisieverts of radiation.

Okay. So calibrate, calibrate me because... That's 40% of your annual allotment. Oh, wow. So the medical practitioners really are the major culprits here. That's right. So what we say is, and I think most doctors are now realizing this is, no, no, it behooves you to pay a little bit more to go to a really good place that can do that scan for two millisieverts.

Meaning they have a much faster CT scanner, much better software, and they're better engineers. So they have better engineering that they can do on the scanner to get that done. So if someone listening to this, here's my take. Do not get a CT scan or any imaging study without asking, how much radiation am I seeing?

And if a person can't tell you how many millisieverts of radiation you're being exposed to, then just say, I'm going to wait a minute until somebody can tell me that. I realize... And keep in mind, if 50 is the most you should ever be exposed to in a year, there better be a damn good reason why I'm going to get 25 in a day.

Now, there are some people who have to do this. If you're a cancer patient and they're scanning you as a part of your treatment, you have to pick and choose between those two opportunities. So I also don't want to create some fear mongering where, oh my God, if you hit 50 in a year, you're hosed.

No, it's just I wouldn't want to hit 50 a year every year for my whole life. And I certainly wouldn't want to be hitting hundreds a year for any period of time. I think we're just trying to raise awareness and also calibrate people to what the sources are and so they can make good choices, not to place them into a chronic state of fear.