WEBVTT 1 00:00:00.000 --> 00:00:01.350 Hi everyone. 2 00:00:01.350 --> 00:00:04.950 In today's lecture, we'll be discussing cancer risk factors. 3 00:00:04.950 --> 00:00:07.650 To begin with, we have three goals of today's lecture 4 00:00:07.650 --> 00:00:10.320 to identify risk factors contributing to various kinds 5 00:00:10.320 --> 00:00:13.590 of cancers to describe the unique role of tobacco use 6 00:00:13.590 --> 00:00:16.470 in cancer ideology, and to summarize the importance 7 00:00:16.470 --> 00:00:18.810 of including questions about exposures to various 8 00:00:18.810 --> 00:00:21.480 risk factors in epidemiological studies. 9 00:00:21.480 --> 00:00:24.540 So to begin with, cancer is caused by what we call 10 00:00:24.540 --> 00:00:26.610 a web of causation. 11 00:00:26.610 --> 00:00:30.110 So that just means that it's due to the cumulative 12 00:00:30.110 --> 00:00:33.750 effects of multiple causal factors 13 00:00:33.750 --> 00:00:36.450 that are going to eventually cause cancer. 14 00:00:36.450 --> 00:00:38.790 It's difficult to establish a definitive proof 15 00:00:38.790 --> 00:00:42.510 of causality but an international panel 16 00:00:42.510 --> 00:00:45.120 of scientists created what's called the criteria 17 00:00:45.120 --> 00:00:48.682 of judgment, which is a tool or a series of questions 18 00:00:48.682 --> 00:00:51.037 that can be used to establish the causality 19 00:00:51.037 --> 00:00:52.263 of a disease. 20 00:00:53.250 --> 00:00:56.430 So in this web of causation we have five 21 00:00:56.430 --> 00:00:57.900 criteria of judgment. 22 00:00:57.900 --> 00:01:00.960 So the first is that multiple independent studies 23 00:01:00.960 --> 00:01:04.320 have confirmed or are consistent about the direction 24 00:01:04.320 --> 00:01:05.880 of an association. 25 00:01:05.880 --> 00:01:09.210 The second is that the strength of the association 26 00:01:09.210 --> 00:01:11.100 in dose response of increasing risk 27 00:01:11.100 --> 00:01:13.080 with increasing exposure. 28 00:01:13.080 --> 00:01:15.300 The third is that there's a temporal relationship 29 00:01:15.300 --> 00:01:17.040 between exposure and pathogenesis. 30 00:01:17.040 --> 00:01:22.040 That is the exposure happens before the event occurs 31 00:01:23.310 --> 00:01:25.920 or the disease begins. 32 00:01:25.920 --> 00:01:28.020 The fourth is that there's a biological plausibility 33 00:01:28.020 --> 00:01:30.350 of this association, and the fifth is that there's coherence 34 00:01:30.350 --> 00:01:32.130 of the association when the totality 35 00:01:32.130 --> 00:01:33.660 of evidence is considered. 36 00:01:33.660 --> 00:01:36.810 So these criteria really emphasize that when determining 37 00:01:36.810 --> 00:01:39.060 whether something causes something else, you're looking 38 00:01:39.060 --> 00:01:41.460 at a number of different independent epidemiological, 39 00:01:41.460 --> 00:01:46.020 biological studies that are going to help determine 40 00:01:46.020 --> 00:01:50.373 or paint a picture of what a causal effect might be. 41 00:01:52.230 --> 00:01:55.110 So of all cancer related deaths, 30% are due 42 00:01:55.110 --> 00:01:58.110 to chronic tobacco Smoking, 30 to 35% 43 00:01:58.110 --> 00:02:00.030 are due to dietary factors. 44 00:02:00.030 --> 00:02:03.450 15% to 20% are due to cancer causing infectious agents 45 00:02:03.450 --> 00:02:06.840 and 3% to 4% are due to alcohol abuse. 46 00:02:06.840 --> 00:02:10.050 It's also notable that only five to 10% of cancers 47 00:02:10.050 --> 00:02:13.050 can be attributed to heritable genetic factors 48 00:02:13.050 --> 00:02:16.110 whereas the remaining 90 to 95% are related 49 00:02:16.110 --> 00:02:18.513 to environment and lifestyle factors. 50 00:02:19.920 --> 00:02:23.310 So this graph just depicts what I just mentioned 51 00:02:23.310 --> 00:02:26.340 and you can see infection diet and tobacco use are really 52 00:02:26.340 --> 00:02:29.721 the three main drivers or causal factors of cancer. 53 00:02:29.721 --> 00:02:32.910 So now let's dig into one of them. 54 00:02:32.910 --> 00:02:36.090 So tobacco smoking is the dominant cancer risk factor. 55 00:02:36.090 --> 00:02:38.430 During the 20th century, approximately 50 million 56 00:02:38.430 --> 00:02:41.310 people died from tobacco-related cancers. 57 00:02:41.310 --> 00:02:44.190 Approximately 50% of regular chronic smokers eventually 58 00:02:44.190 --> 00:02:47.820 succumb to tobacco related cancer and most die prematurely. 59 00:02:47.820 --> 00:02:51.300 And cigarette smoking causes about 30% of all cancer 60 00:02:51.300 --> 00:02:53.580 death making tobacco smoke the single most 61 00:02:53.580 --> 00:02:55.920 lethal source of carcinogens. 62 00:02:55.920 --> 00:02:58.127 Tobacco use has unfortunately continued to rise 63 00:02:58.127 --> 00:03:01.127 globally, and it is one of the greatest 64 00:03:01.127 --> 00:03:05.280 global public health challenges of our time. 65 00:03:05.280 --> 00:03:08.580 Recent survey data compiled from 193 member nations 66 00:03:08.580 --> 00:03:13.580 of the WHO showed that one in three adults smoke globally. 67 00:03:16.290 --> 00:03:19.587 So now we come to the 1964 US Surgeon General's Report 68 00:03:19.587 --> 00:03:21.000 on "Smoking and Health." 69 00:03:21.000 --> 00:03:23.790 And this was a landmark study that unequivocably 70 00:03:23.790 --> 00:03:26.490 linked tobacco to lung cancer, laryngeal cancer 71 00:03:26.490 --> 00:03:29.760 and a number of other severe adverse health outcomes. 72 00:03:29.760 --> 00:03:32.400 This report highlighted the many delirious health 73 00:03:32.400 --> 00:03:36.480 consequences of chronic cigarette smoking and tobacco use. 74 00:03:36.480 --> 00:03:38.700 Specifically, it showed that chronic smoking 75 00:03:38.700 --> 00:03:41.070 was linked to lung cancer, laryngeal cancer, 76 00:03:41.070 --> 00:03:46.070 chronic bronchitis, emphysema and coronary heart disease. 77 00:03:46.170 --> 00:03:48.960 The 1964 Surgeon General's report and many 78 00:03:48.960 --> 00:03:51.270 subsequent reports, have had a major impact 79 00:03:51.270 --> 00:03:54.240 on public attitudes and policy about smoking in America 80 00:03:54.240 --> 00:03:57.150 and most other developed nations. 81 00:03:57.150 --> 00:03:59.460 So after this report was published 82 00:03:59.460 --> 00:04:01.140 the percentage of adults who smoked cigarettes 83 00:04:01.140 --> 00:04:06.140 in the US declined from 42% in 1964 to only 18% in 2012. 84 00:04:07.890 --> 00:04:09.930 This means that 8 million premature smoking 85 00:04:09.930 --> 00:04:12.690 related deaths were prevented in the US population 86 00:04:12.690 --> 00:04:15.180 during the past 50 years. 87 00:04:15.180 --> 00:04:17.820 So after the 1964 report was published there was 88 00:04:17.820 --> 00:04:20.640 a 2020 Surgeon General's report on smoking cessation 89 00:04:20.640 --> 00:04:21.900 that was published. 90 00:04:21.900 --> 00:04:23.333 This report makes it clear that one of the most 91 00:04:23.333 --> 00:04:25.560 important actions people can take to improve 92 00:04:25.560 --> 00:04:27.600 their health is to quit smoking. 93 00:04:27.600 --> 00:04:30.120 This is true regardless of one's age or of how long 94 00:04:30.120 --> 00:04:33.060 they've been smoking, there are proven treatments 95 00:04:33.060 --> 00:04:35.790 and strategies to help people quit smoking successfully. 96 00:04:35.790 --> 00:04:38.880 And this report really describes those efforts 97 00:04:38.880 --> 00:04:42.089 and emphasizes the importance of treatment 98 00:04:42.089 --> 00:04:46.530 use of medications and ultimately the health benefits 99 00:04:46.530 --> 00:04:50.583 that can can accrue from quitting smoking tobacco use. 100 00:04:52.380 --> 00:04:56.190 So next, this figure from your textbook shows the number 101 00:04:56.190 --> 00:04:59.310 of worldwide deaths attributed to cigarette smoking 102 00:04:59.310 --> 00:05:02.760 and 5.4 million of the 1.1 billion adults who are 103 00:05:02.760 --> 00:05:05.430 chronically addicted to the smoking habit die annually 104 00:05:05.430 --> 00:05:08.520 from lung cancer and other smoking related diseases, 105 00:05:08.520 --> 00:05:11.160 like heart disease, chronic obstructive pulmonary disease 106 00:05:11.160 --> 00:05:14.493 or COPD, stroke and other cancers. 107 00:05:16.043 --> 00:05:20.040 Compared to non-smoker, chronic smokers have a 10 to 40 108 00:05:20.040 --> 00:05:23.250 fold increased risk of developing lung cancer. 109 00:05:23.250 --> 00:05:25.980 Worldwide approximately 90% of lung cancers 110 00:05:25.980 --> 00:05:28.650 are attributable to cigarette smoking. 111 00:05:28.650 --> 00:05:31.350 Chronic tobacco use markedly increases the risk 112 00:05:31.350 --> 00:05:34.050 of cancer development at many other anatomic sites 113 00:05:34.050 --> 00:05:37.860 including the oral cavity, larynx, pharynx, nasal cavity 114 00:05:37.860 --> 00:05:41.270 esophagus, stomach, kidney, urinary bladder, pancreas, 115 00:05:41.270 --> 00:05:43.920 liver and uterine cervix. 116 00:05:43.920 --> 00:05:46.170 And finally, smoking has also been implicated 117 00:05:46.170 --> 00:05:48.570 in the development of certain types of leukemia. 118 00:05:49.590 --> 00:05:52.260 In the US, we're also seeing that more women now die 119 00:05:52.260 --> 00:05:55.500 from smoking induced lung cancer than from breast cancer. 120 00:05:55.500 --> 00:05:57.930 There's a huge rise in female smoking 121 00:05:57.930 --> 00:06:00.780 and that's an important public health concern. 122 00:06:00.780 --> 00:06:03.150 In the Nordic countries like Iceland and Denmark, 123 00:06:03.150 --> 00:06:05.970 more women are now dying from lung cancer than men, 124 00:06:05.970 --> 00:06:08.910 and in several European countries 50% of young women 125 00:06:08.910 --> 00:06:12.180 are regular smokers, and such high rates will inevitably 126 00:06:12.180 --> 00:06:14.220 produce an incredible burden of lung cancer 127 00:06:14.220 --> 00:06:15.780 and other smoking related diseases 128 00:06:15.780 --> 00:06:17.733 in women for centuries to come. 129 00:06:19.470 --> 00:06:21.510 Diet and cancer in high income countries 130 00:06:21.510 --> 00:06:23.700 is also a critical concern. 131 00:06:23.700 --> 00:06:26.850 In high income countries, animal or saturated fat 132 00:06:26.850 --> 00:06:29.460 in certain polyunsaturated fatty acids are associated 133 00:06:29.460 --> 00:06:31.470 with cancers of the breasts, prostate 134 00:06:31.470 --> 00:06:33.210 and lower gastrointestinal tract. 135 00:06:33.210 --> 00:06:34.860 The colon and the rectum. 136 00:06:34.860 --> 00:06:37.140 Diets high in fat and low in fiber are linked 137 00:06:37.140 --> 00:06:40.050 to pathogenesis of colorectal cancer, prostate cancer, 138 00:06:40.050 --> 00:06:41.367 breast cancer, endometrial cancer 139 00:06:41.367 --> 00:06:44.460 and several other cancers. 140 00:06:44.460 --> 00:06:47.188 We also see that the westernized diet 141 00:06:47.188 --> 00:06:50.190 which is commonly described as the intake 142 00:06:50.190 --> 00:06:53.160 of excessive calories from fat, refined carbohydrates 143 00:06:53.160 --> 00:06:55.650 sugar and animal protein in combination 144 00:06:55.650 --> 00:06:57.870 with a sedentary lifestyle can lead to energy 145 00:06:57.870 --> 00:06:59.490 imbalance associated with a multitude 146 00:06:59.490 --> 00:07:02.670 of chronic diseases like obesity, type two diabetes 147 00:07:02.670 --> 00:07:07.140 cardiovascular disease, arterial hypertension, and cancer. 148 00:07:07.140 --> 00:07:10.920 We also see that obesity is linked to a number of cancers. 149 00:07:10.920 --> 00:07:13.650 In low and middle income countries, or LMICs. 150 00:07:13.650 --> 00:07:16.687 We see differences in the dietary risks 151 00:07:16.687 --> 00:07:19.470 than we see from high income countries. 152 00:07:19.470 --> 00:07:20.760 So we see that there are certain types 153 00:07:20.760 --> 00:07:23.520 of toxins that people can be exposed 154 00:07:23.520 --> 00:07:26.070 to by ingesting moldy grains. 155 00:07:26.070 --> 00:07:29.130 For example, aflatoxins when people consume them 156 00:07:29.130 --> 00:07:30.900 are metabolized by the liver and become highly 157 00:07:30.900 --> 00:07:33.360 carcinogenic epoxides. 158 00:07:33.360 --> 00:07:36.510 We also see that chronic exposure to these toxins is related 159 00:07:36.510 --> 00:07:38.550 to liver cancer, which is the leading cause of death 160 00:07:38.550 --> 00:07:41.500 in some populations in southern China, southeast Asia 161 00:07:41.500 --> 00:07:43.773 and coastal regions of Africa. 162 00:07:45.240 --> 00:07:49.320 It's also important to note that some dietary factors 163 00:07:49.320 --> 00:07:52.380 can interact with other cancer risk factors. 164 00:07:52.380 --> 00:07:55.260 So aflatoxins and hepatitis viruses that is 165 00:07:55.260 --> 00:07:57.570 hep B and Hep C interact synergistically 166 00:07:57.570 --> 00:07:59.553 in the pathogenesis of liver cancer. 167 00:08:00.660 --> 00:08:03.330 We also see that regular exposure to irritants, spices 168 00:08:03.330 --> 00:08:05.790 and hot beverages can produce chronic inflammation 169 00:08:05.790 --> 00:08:07.710 of the squamous cell lining of the esophagus 170 00:08:07.710 --> 00:08:09.990 and can cause dysplastic lesions. 171 00:08:09.990 --> 00:08:12.420 That's why in some communities where the consumption 172 00:08:12.420 --> 00:08:15.450 of hot beverages like tea or coffee are common 173 00:08:15.450 --> 00:08:18.900 especially extremely hot temperatures, like right 174 00:08:18.900 --> 00:08:21.870 after the water boils, we see elevated rates 175 00:08:21.870 --> 00:08:24.420 of esophageal cancer or other cancers 176 00:08:24.420 --> 00:08:26.643 of the upper digestive tract. 177 00:08:27.570 --> 00:08:30.720 So as I noted, the practice of ingesting hot 178 00:08:30.720 --> 00:08:33.540 spicy beverages is commonplace in many cultures 179 00:08:33.540 --> 00:08:36.150 in communities in East Asia, in the Middle East 180 00:08:36.150 --> 00:08:38.883 which contributes to esophageal cancer rates. 181 00:08:40.560 --> 00:08:44.070 Turning to alcohol, chronic alcohol use is a risk factor 182 00:08:44.070 --> 00:08:46.890 for a number of cancers, including cancer of the oral cavity 183 00:08:46.890 --> 00:08:49.830 the esophagus, the liver, and the pancreas. 184 00:08:49.830 --> 00:08:52.020 Alcohol can also interject synergistically 185 00:08:52.020 --> 00:08:55.020 with chronic cigarette smoking that can again 186 00:08:55.020 --> 00:08:57.543 increase the risk of cancers in some sites. 187 00:08:59.400 --> 00:09:02.190 Next, we see that in low and middle income countries 188 00:09:02.190 --> 00:09:04.830 more than 20% of cancers and related deaths are caused 189 00:09:04.830 --> 00:09:07.080 by infectious agents that cause cervical cancer 190 00:09:07.080 --> 00:09:10.950 liver cancer, stomach cancer, and other kinds of cancers. 191 00:09:10.950 --> 00:09:14.910 Especially in China, Asia and Africa we see various 192 00:09:14.910 --> 00:09:16.680 infectious agents playing a role. 193 00:09:16.680 --> 00:09:21.020 These include hepatitis viruses human papilloma viruses 194 00:09:21.020 --> 00:09:25.284 or HPV, Helicobacter pylorus, schistosomiasis, 195 00:09:25.284 --> 00:09:28.620 co-infection by HIV and herpes B 196 00:09:28.620 --> 00:09:32.970 or herpes virus eight rather, and malaria, 197 00:09:32.970 --> 00:09:35.700 which can be linked to Burkett's Lymphoma. 198 00:09:35.700 --> 00:09:39.150 In regions with high HPV infection rates 199 00:09:39.150 --> 00:09:41.820 and cervical screening programs or a lack rather 200 00:09:41.820 --> 00:09:43.560 of cervical screening programs. 201 00:09:43.560 --> 00:09:48.560 Cervical cancer ranks first as a cause of cancer death. 202 00:09:48.750 --> 00:09:51.030 We also see that more than 80% of all cervical 203 00:09:51.030 --> 00:09:53.910 cancer deaths today occur in low and middle income countries 204 00:09:53.910 --> 00:09:57.690 due to this duality of high rates of HPV 205 00:09:57.690 --> 00:09:59.880 and low rates of screening. 206 00:09:59.880 --> 00:10:02.280 Finally, we see the chronic infections account 207 00:10:02.280 --> 00:10:05.100 for less than 10% of all malignancies in high income 208 00:10:05.100 --> 00:10:09.060 countries, and that's due to more screening programs, 209 00:10:09.060 --> 00:10:10.500 vaccination, et cetera. 210 00:10:10.500 --> 00:10:13.290 So stomach cancer declined in many nations 211 00:10:13.290 --> 00:10:15.030 due to the replacement of irritating preservatives 212 00:10:15.030 --> 00:10:18.660 by refrigeration and ready access to fruits and vegetables. 213 00:10:18.660 --> 00:10:22.369 So lowering the chance of infection with bacteria 214 00:10:22.369 --> 00:10:24.990 or molds or other agents. 215 00:10:24.990 --> 00:10:28.380 Cervical cancer rates have decreased due to an increase 216 00:10:28.380 --> 00:10:30.510 in the use of the Pap test. 217 00:10:30.510 --> 00:10:33.750 And finally rates of liver cancer have declined 218 00:10:33.750 --> 00:10:35.640 in China and Thailand due to effective 219 00:10:35.640 --> 00:10:38.460 immunization programs to prevent viral hepatitis 220 00:10:38.460 --> 00:10:41.310 and improve storage conditions of staple foods 221 00:10:41.310 --> 00:10:43.443 to reduce exposure to toxins.