WEBVTT 1 00:00:00.480 --> 00:00:01.410 Hi, y'all. 2 00:00:01.410 --> 00:00:02.820 In this lecture, we'll be discussing 3 00:00:02.820 --> 00:00:04.893 the epidemiology of pancreatic cancer. 4 00:00:05.730 --> 00:00:07.980 Our goals for this lecture are to review studies 5 00:00:07.980 --> 00:00:10.230 of coffee and pancreatic cancer, 6 00:00:10.230 --> 00:00:12.840 to review the anatomy and function of the pancreas, 7 00:00:12.840 --> 00:00:15.570 to describe the global burden of pancreatic cancer, 8 00:00:15.570 --> 00:00:18.150 review key studies of tobacco and alcohol, 9 00:00:18.150 --> 00:00:21.510 describe the role of pancreatitis and pancreatic cancer, 10 00:00:21.510 --> 00:00:23.730 review key studies of dietary fat, 11 00:00:23.730 --> 00:00:26.220 describe how bile acids promote pancreatic cancer, 12 00:00:26.220 --> 00:00:28.710 and finally to discuss prevention and control 13 00:00:28.710 --> 00:00:30.543 of pancreatic cancer. 14 00:00:31.620 --> 00:00:34.020 So to begin with, an article was published 15 00:00:34.020 --> 00:00:37.440 on March 12th, 1981, showing a statistical link 16 00:00:37.440 --> 00:00:40.710 between the drinking of coffee and cancer of the pancreas, 17 00:00:40.710 --> 00:00:42.240 which is the fourth most common cause 18 00:00:42.240 --> 00:00:44.283 of cancer death among Americans. 19 00:00:45.180 --> 00:00:46.830 This discovery was unexpected 20 00:00:46.830 --> 00:00:49.440 and the significance is not yet clear. 21 00:00:49.440 --> 00:00:53.250 The report wrote that it reflects a causal relation 22 00:00:53.250 --> 00:00:55.860 between coffee drinking and pancreatic cancer, 23 00:00:55.860 --> 00:00:57.450 and that coffee use might account 24 00:00:57.450 --> 00:00:58.500 for a substantial proportion 25 00:00:58.500 --> 00:01:00.843 of the cases of pancreatic cancer in the US. 26 00:01:02.130 --> 00:01:03.180 The report was published 27 00:01:03.180 --> 00:01:04.500 in the "New England Journal of Medicine", 28 00:01:04.500 --> 00:01:06.183 a prestigious medical journal. 29 00:01:07.620 --> 00:01:09.630 Although the statistical association in the study 30 00:01:09.630 --> 00:01:11.943 does not prove that coffee causes cancer, 31 00:01:13.470 --> 00:01:15.780 one of the investigators in the study 32 00:01:15.780 --> 00:01:17.610 stopped drinking coffee 33 00:01:17.610 --> 00:01:21.150 because of the potential relationship 34 00:01:21.150 --> 00:01:23.013 between coffee and pancreatic cancer. 35 00:01:25.410 --> 00:01:27.540 The study was a case control study 36 00:01:27.540 --> 00:01:30.520 and it looked at 360 cases 37 00:01:31.500 --> 00:01:35.130 and 643 group matched hospital controls 38 00:01:35.130 --> 00:01:36.540 who were treated by the same physicians 39 00:01:36.540 --> 00:01:38.430 who treated the cases. 40 00:01:38.430 --> 00:01:41.850 We see that of the cases, 20 consumed coffee, 41 00:01:41.850 --> 00:01:45.750 or 20 did not consume coffee and 347 did consume coffee, 42 00:01:45.750 --> 00:01:48.480 whereas in the control, it was 555 consumed coffee 43 00:01:48.480 --> 00:01:51.450 and 88 did not consume coffee. 44 00:01:51.450 --> 00:01:54.210 Many investigations after this one 45 00:01:54.210 --> 00:01:55.800 failed to confirm the association 46 00:01:55.800 --> 00:02:00.390 observed in the first 1981 study, so it's generally accepted 47 00:02:00.390 --> 00:02:02.040 that there's no causal association 48 00:02:02.040 --> 00:02:04.500 between coffee and cancer of the pancreas. 49 00:02:04.500 --> 00:02:07.680 If we remember Hill's criteria of causality, 50 00:02:07.680 --> 00:02:10.600 we know that causal relationships are only determined 51 00:02:11.820 --> 00:02:14.220 by looking at the full balance of evidence 52 00:02:14.220 --> 00:02:16.070 through multiple independent studies. 53 00:02:17.760 --> 00:02:20.460 So to turn to the anatomy and function of the pancreas, 54 00:02:20.460 --> 00:02:22.440 we see that the pancreas is a dual functioning gland 55 00:02:22.440 --> 00:02:25.890 located deep in the abdomen just behind the stomach. 56 00:02:25.890 --> 00:02:27.600 Numerous pancreatic ducts communicate 57 00:02:27.600 --> 00:02:29.340 with the main's pancreatic duct 58 00:02:29.340 --> 00:02:31.410 that merges with the common bile duct 59 00:02:31.410 --> 00:02:35.220 to form the ampulla of Vater that empties into the duodenum, 60 00:02:35.220 --> 00:02:37.470 which is the upper small intestine. 61 00:02:37.470 --> 00:02:40.650 The pancreas is an endocrine and exocrine gland, 62 00:02:40.650 --> 00:02:42.990 and specialized endocrine cells 63 00:02:42.990 --> 00:02:45.270 called the islets of Langerhans are instrumental 64 00:02:45.270 --> 00:02:47.910 in the secretion of insulin and glucagon 65 00:02:47.910 --> 00:02:51.120 to maintain tight control of blood glucose. 66 00:02:51.120 --> 00:02:53.970 There are other exocrine cells called acinar cells 67 00:02:53.970 --> 00:02:55.920 that support powerful digestive enzymes 68 00:02:55.920 --> 00:02:57.810 like trypsin, lipase, and amylase, 69 00:02:57.810 --> 00:03:00.540 as well as alkaline fluid into the pancreatic ducts 70 00:03:00.540 --> 00:03:03.300 that eventually drain into the main pancreatic duct 71 00:03:03.300 --> 00:03:04.413 and the duodenum. 72 00:03:05.430 --> 00:03:07.950 The digestive enzymes secreted by the pancreas 73 00:03:07.950 --> 00:03:10.323 break down protein, fats, and carbohydrates. 74 00:03:12.480 --> 00:03:14.470 So the incidence of pancreatic cancer 75 00:03:16.710 --> 00:03:20.730 shows clear patterns of high incidence in the US, 76 00:03:20.730 --> 00:03:22.290 in Argentina, in Australia, 77 00:03:22.290 --> 00:03:24.790 and some parts of Central Asia and Western Europe. 78 00:03:29.760 --> 00:03:32.800 Similarly, mortality rates 79 00:03:33.720 --> 00:03:37.200 are similarly high in parts of Western Europe, 80 00:03:37.200 --> 00:03:40.833 Russia, Argentina, the US, and South Africa. 81 00:03:42.180 --> 00:03:43.080 Pancreatic cancer 82 00:03:43.080 --> 00:03:46.110 accounts for about 2% of all cancers in the US 83 00:03:46.110 --> 00:03:47.610 and it's uniformly fatal. 84 00:03:47.610 --> 00:03:49.860 It's the fourth leading cause of cancer deaths. 85 00:03:49.860 --> 00:03:53.190 The peak incidence is at age 60 to 65 years, 86 00:03:53.190 --> 00:03:56.343 when it's an incidence of 60 per 100,000 people. 87 00:03:57.930 --> 00:04:01.410 In 2020 in the US, the overall incidence was 4.9 88 00:04:01.410 --> 00:04:02.793 per 100,000 people, 89 00:04:03.660 --> 00:04:06.179 with an incidence of 5.7 per 100,000 90 00:04:06.179 --> 00:04:08.490 and 4.1 per 100,000 women. 91 00:04:08.490 --> 00:04:13.490 The mortality is 4.5 per 100,000 overall total population, 92 00:04:13.920 --> 00:04:18.920 and 5.3 per 100,000 men and 3.8 per 100,000 women. 93 00:04:19.410 --> 00:04:21.510 Key risk factors for pancreatic cancer 94 00:04:21.510 --> 00:04:24.270 include alcohol abuse, biliary obstruction, 95 00:04:24.270 --> 00:04:26.613 chronic pancreatitis, 96 00:04:27.450 --> 00:04:28.800 diabetes, obesity, 97 00:04:28.800 --> 00:04:32.100 a high fat diet, and chronic tobacco smoking. 98 00:04:32.100 --> 00:04:33.840 As we can see from this figure, 99 00:04:33.840 --> 00:04:36.022 the risk of pancreatic cancer greatly increases 100 00:04:36.022 --> 00:04:38.700 with the number of cigarettes per day. 101 00:04:38.700 --> 00:04:40.920 That is, individuals smoking 40, 102 00:04:40.920 --> 00:04:42.810 or more than 40 cigarettes per day 103 00:04:42.810 --> 00:04:46.170 have 4.5 times the chances of developing pancreatic cancer 104 00:04:46.170 --> 00:04:48.123 than those who do not smoke cigarettes. 105 00:04:49.470 --> 00:04:52.690 There's also acute and chronic pancreatitis 106 00:04:52.690 --> 00:04:57.360 that can play a role in the causation of pancreatic cancer. 107 00:04:57.360 --> 00:04:59.340 So acute pancreatitis 108 00:04:59.340 --> 00:05:01.110 is defined as the inflammation, hemorrhage, 109 00:05:01.110 --> 00:05:04.110 and necrosis of the pancreas, While chronic pancreatitis 110 00:05:04.110 --> 00:05:07.410 is progressive relapsing acute pancreatitis. 111 00:05:07.410 --> 00:05:09.660 Signs and symptoms of acute pancreatitis 112 00:05:09.660 --> 00:05:11.460 include abdominal pain, hemorrhage, 113 00:05:11.460 --> 00:05:14.730 fat necrosis, jaundice or yellowing of the skin, 114 00:05:14.730 --> 00:05:16.860 ascites, and shock. 115 00:05:16.860 --> 00:05:21.390 The treatment for acute pancreatitis is the pain control, 116 00:05:21.390 --> 00:05:23.970 going to the emergency department of the hospital, 117 00:05:23.970 --> 00:05:25.770 NPO, and surgery. 118 00:05:25.770 --> 00:05:29.670 Chronic pancreatitis can be treated by changes in diet, 119 00:05:29.670 --> 00:05:34.503 abstaining from alcohol, and cholecystectomy. 120 00:05:37.350 --> 00:05:40.110 Alcohol is related to pancreatic cancer 121 00:05:40.110 --> 00:05:42.300 in a dose-dependent fashion. 122 00:05:42.300 --> 00:05:44.430 There is a two to threefold increased risk 123 00:05:44.430 --> 00:05:46.230 of pancreatic cancer in heavy drinkers 124 00:05:46.230 --> 00:05:48.230 who consume four or more drinks per day. 125 00:05:49.590 --> 00:05:53.340 Alcohol is an independent risk factor for pancreatic cancer, 126 00:05:53.340 --> 00:05:55.800 and chronic alcohol abuse causes pancreatitis, 127 00:05:55.800 --> 00:05:59.370 which can then transform into invasive pancreatic cancer. 128 00:05:59.370 --> 00:06:01.290 The progressive cascade of pathogenic events 129 00:06:01.290 --> 00:06:03.210 in chronic alcoholic pancreatitis 130 00:06:03.210 --> 00:06:05.550 involves chronic inflammation, cell necrosis 131 00:06:05.550 --> 00:06:07.230 release of digestive enzymes, 132 00:06:07.230 --> 00:06:11.100 cell autodigestion, formation of reactive oxygen species, 133 00:06:11.100 --> 00:06:12.840 collagen deposition, fibrosis, 134 00:06:12.840 --> 00:06:14.310 scarring of the pancreatic tissues, 135 00:06:14.310 --> 00:06:16.173 and transformation to neoplasia. 136 00:06:17.100 --> 00:06:19.650 Chronic pancreatitis refers to the persistent inflammation 137 00:06:19.650 --> 00:06:23.250 of the pancreas irrespective of the cause. 138 00:06:23.250 --> 00:06:25.230 It's a strong risk factor for the development 139 00:06:25.230 --> 00:06:26.643 of pancreatic cancer, 140 00:06:28.500 --> 00:06:29.973 and the risk increase, 141 00:06:31.050 --> 00:06:35.250 the risk of pancreatic cancer associated with pancreatitis 142 00:06:35.250 --> 00:06:36.300 is independent of gender, 143 00:06:36.300 --> 00:06:39.690 country of origin, and type of pancreatitis. 144 00:06:39.690 --> 00:06:41.640 The main cause of chronic pancreatitis 145 00:06:41.640 --> 00:06:43.260 is chronic alcohol abuse. 146 00:06:43.260 --> 00:06:46.020 More than 70% of adult patients with chronic pancreatitis 147 00:06:46.020 --> 00:06:48.780 have a history of excessive alcohol intake. 148 00:06:48.780 --> 00:06:50.730 The majority of patients report daily consumption 149 00:06:50.730 --> 00:06:53.943 of at least 150 grams of alcohol for more than five years. 150 00:06:56.910 --> 00:06:59.760 Type 2 diabetes is also a key risk factor 151 00:06:59.760 --> 00:07:01.290 for pancreatic cancer. 152 00:07:01.290 --> 00:07:04.470 The twin epidemics of obesity and diabetes mellitus type 2 153 00:07:04.470 --> 00:07:07.290 have emerged in many populations throughout the world. 154 00:07:07.290 --> 00:07:09.030 Both conditions are independently associated 155 00:07:09.030 --> 00:07:10.650 with the development of pancreatic cancer, 156 00:07:10.650 --> 00:07:13.680 and obesity is associated with the onset of diabetes. 157 00:07:13.680 --> 00:07:16.080 Meta-analysis of epidemiologic studies 158 00:07:16.080 --> 00:07:18.570 show a twofold elevation in the risk of pancreatic cancer 159 00:07:18.570 --> 00:07:20.760 among individuals with a five year history 160 00:07:20.760 --> 00:07:22.770 of type 2 diabetes. 161 00:07:22.770 --> 00:07:24.960 Currently, however, there's no general consensus 162 00:07:24.960 --> 00:07:26.610 as to a cause and effect relationship 163 00:07:26.610 --> 00:07:29.730 between type 2 diabetes and pancreatic cancer. 164 00:07:29.730 --> 00:07:31.620 One argument against such a relationship 165 00:07:31.620 --> 00:07:33.810 is the fact that rates of pancreatic cancer 166 00:07:33.810 --> 00:07:36.630 have remained constant or declined in many nations, 167 00:07:36.630 --> 00:07:39.120 even though prevalence rates of obesity and type 2 diabetes 168 00:07:39.120 --> 00:07:41.100 have increased dramatically. 169 00:07:41.100 --> 00:07:42.480 Nevertheless, in subjects 170 00:07:42.480 --> 00:07:44.130 with longstanding type two 2 diabetes, 171 00:07:44.130 --> 00:07:47.130 the pancreas is chronically exposed to hyperinsulinemia, 172 00:07:47.130 --> 00:07:49.050 and since cultures of pancreatic cancer cells 173 00:07:49.050 --> 00:07:51.270 have been found to express insulin receptors, 174 00:07:51.270 --> 00:07:53.580 it's possible that hyperinsulinemia could serve 175 00:07:53.580 --> 00:07:55.623 as a promoter of pancreatic cancer. 176 00:07:56.640 --> 00:07:58.020 A major problem with studies 177 00:07:58.020 --> 00:08:00.060 of the association of pancreatic cancer and diabetes 178 00:08:00.060 --> 00:08:01.650 is that since both conditions evolve 179 00:08:01.650 --> 00:08:03.810 in the same organ over a period of many years, 180 00:08:03.810 --> 00:08:06.393 it's difficult to determine the causal pathway. 181 00:08:08.070 --> 00:08:09.210 There's also an association 182 00:08:09.210 --> 00:08:11.790 between dietary fat and pancreatic cancer. 183 00:08:11.790 --> 00:08:13.140 The US National Institutes 184 00:08:13.140 --> 00:08:15.210 of Health American Association of Retired Persons, 185 00:08:15.210 --> 00:08:17.580 or AARP, Diet and Health Study 186 00:08:17.580 --> 00:08:19.350 was designed to provide definitive evidence 187 00:08:19.350 --> 00:08:21.090 and dietary risk factors in the development 188 00:08:21.090 --> 00:08:22.800 of a variety of chronic diseases, 189 00:08:22.800 --> 00:08:24.603 including pancreatic cancer. 190 00:08:25.950 --> 00:08:29.820 The investigation of the relationship between dietary fat 191 00:08:29.820 --> 00:08:34.740 and pancreatic cancer was based upon a cohort of 308,736 men 192 00:08:34.740 --> 00:08:38.820 and 216,737 women 193 00:08:38.820 --> 00:08:41.130 aged 51 to 70 years of age 194 00:08:41.130 --> 00:08:43.440 who completed a food frequency questionnaire 195 00:08:43.440 --> 00:08:45.423 between 1995 and 1996. 196 00:08:46.290 --> 00:08:48.060 The study found that pancreatic cancer risk 197 00:08:48.060 --> 00:08:50.460 increased with high intake of total fat, 198 00:08:50.460 --> 00:08:53.280 saturated fat, or monounsaturated fat. 199 00:08:53.280 --> 00:08:55.560 The risk was highest for high intake of saturated fat 200 00:08:55.560 --> 00:08:57.093 from animal food sources, 201 00:08:57.990 --> 00:08:59.610 and results suggest that high intake 202 00:08:59.610 --> 00:09:02.160 of dietary fat of animal origin increases the risk 203 00:09:02.160 --> 00:09:04.443 of developing pancreatic cancer. 204 00:09:05.490 --> 00:09:07.920 The possible pathogenesis behind this 205 00:09:07.920 --> 00:09:09.420 is that diets with high fat content 206 00:09:09.420 --> 00:09:11.580 stimulate or stimulate bios secretion 207 00:09:11.580 --> 00:09:13.620 by the liver and biliary tract. 208 00:09:13.620 --> 00:09:14.940 Bio acids have been found 209 00:09:14.940 --> 00:09:17.880 to induce cyclooxygenase two or COX-2 210 00:09:17.880 --> 00:09:21.630 and lead to inflammation in pancreatic cancer cell lines. 211 00:09:21.630 --> 00:09:23.718 This inflammation can then lead 212 00:09:23.718 --> 00:09:26.463 to carcinogenic mutagenesis. 213 00:09:28.350 --> 00:09:30.840 So approximately 99% of pancreatic cancers 214 00:09:30.840 --> 00:09:32.340 evolve from the ductal epithelium 215 00:09:32.340 --> 00:09:34.830 and only 1% arise from acini. 216 00:09:34.830 --> 00:09:37.530 Pancreatic carcinogenesis involves chronic inflammation 217 00:09:37.530 --> 00:09:40.683 and promotion of cell division without normal apoptosis. 218 00:09:41.970 --> 00:09:45.390 Germline mutations can also be a cause of pancreatic cancer. 219 00:09:45.390 --> 00:09:47.130 Familial breast or ovarian cancer 220 00:09:47.130 --> 00:09:49.650 is often caused by heritable mutation 221 00:09:49.650 --> 00:09:51.630 in either of two tumor suppressor genes, 222 00:09:51.630 --> 00:09:54.330 the BRCA1 or BRCA2 genes. 223 00:09:54.330 --> 00:09:57.000 Females who inherit mutant alleles of one of these genes 224 00:09:57.000 --> 00:09:59.400 are not only at high risk of developing breast cancer 225 00:09:59.400 --> 00:10:02.730 and/or ovarian cancer, but they're also at increased risk 226 00:10:02.730 --> 00:10:04.200 for the development of other tumors, 227 00:10:04.200 --> 00:10:06.510 including pancreatic cancer. 228 00:10:06.510 --> 00:10:10.020 The familial atypical mole and melanoma syndrome or FAMM 229 00:10:10.020 --> 00:10:11.700 is a rare genetic disorder giving rise 230 00:10:11.700 --> 00:10:14.100 to multiple dysplastic pigmented moles of the skin 231 00:10:14.100 --> 00:10:16.440 that can progress to malignant melanoma. 232 00:10:16.440 --> 00:10:19.040 There's also a risk of developing pancreatic cancer. 233 00:10:20.340 --> 00:10:22.020 The Peutz-Jeghers syndrome is a rare 234 00:10:22.020 --> 00:10:23.730 autosomal dominant disorder 235 00:10:23.730 --> 00:10:25.050 characterized by the development 236 00:10:25.050 --> 00:10:28.260 of benign hamartomatous polyps in the gastrointestinal tract 237 00:10:28.260 --> 00:10:31.500 and hyperpigmented macules in the lips and oral mucosa. 238 00:10:31.500 --> 00:10:32.580 This syndrome is caused 239 00:10:32.580 --> 00:10:35.490 by a mutant tumor suppressor gene as well. 240 00:10:35.490 --> 00:10:37.830 Finally, the Lynch syndrome is characterized 241 00:10:37.830 --> 00:10:40.920 by high lifetime risk for the development of colon cancer. 242 00:10:40.920 --> 00:10:43.620 The cause of the syndrome is an inherited mutation 243 00:10:43.620 --> 00:10:47.460 in at least one set of genes that normally repair DNA. 244 00:10:47.460 --> 00:10:49.470 The genetic disorder also carries an increase 245 00:10:49.470 --> 00:10:51.670 in the risk of developing pancreatic cancer. 246 00:10:52.680 --> 00:10:55.860 Somatic mutations involving base pair changes in DNA 247 00:10:55.860 --> 00:10:57.510 occasionally occur in specific cells 248 00:10:57.510 --> 00:10:59.790 of specific tissues of the human body. 249 00:10:59.790 --> 00:11:01.590 The phenotypic effects of such mutations 250 00:11:01.590 --> 00:11:04.293 persist in the lineage of the cell of origin. 251 00:11:05.310 --> 00:11:08.130 Somatic mutations of K-RAS gene have been observed 252 00:11:08.130 --> 00:11:10.020 in up to 90% of certain malignancies, 253 00:11:10.020 --> 00:11:13.470 like colon cancer, lung cancer, and pancreatic cancer. 254 00:11:13.470 --> 00:11:16.260 This gene communicates signals from outside the cell 255 00:11:16.260 --> 00:11:19.560 to the nucleus, a process known as signal transduction. 256 00:11:19.560 --> 00:11:22.590 Because this signal transduction stimulates cell division, 257 00:11:22.590 --> 00:11:24.030 its dysregulation may result 258 00:11:24.030 --> 00:11:25.350 in heightened cell proliferation 259 00:11:25.350 --> 00:11:26.800 and malignant transformation. 260 00:11:29.700 --> 00:11:31.680 Epigenetics are the study of changes 261 00:11:31.680 --> 00:11:32.580 in the expression of genes 262 00:11:32.580 --> 00:11:36.333 without any alteration in the base pair sequence of the DNA. 263 00:11:37.170 --> 00:11:40.230 Is also related to the development of pancreatic cancer. 264 00:11:40.230 --> 00:11:41.700 So in epigenetics, 265 00:11:41.700 --> 00:11:44.070 different genes can be up or downregulated, 266 00:11:44.070 --> 00:11:47.850 and COX-2 upregulation is common in pancreatic cancer cases. 267 00:11:47.850 --> 00:11:49.380 This upregulation of COX-2 268 00:11:49.380 --> 00:11:53.853 can lead to chronic pancreatitis and necroinflammation. 269 00:11:54.810 --> 00:11:58.200 And as we've discussed, inflammation is closely related 270 00:11:58.200 --> 00:11:59.643 to the causation of cancer. 271 00:12:00.900 --> 00:12:04.590 Next, islet cell tumors are a form 272 00:12:04.590 --> 00:12:06.120 related to pancreatic cancer, 273 00:12:06.120 --> 00:12:07.560 and they arise from endocrine cells 274 00:12:07.560 --> 00:12:08.960 in the islets of Langerhans. 275 00:12:10.080 --> 00:12:11.550 Most are beta cell tumors, 276 00:12:11.550 --> 00:12:14.220 since the beta cells elaborate insulin. 277 00:12:14.220 --> 00:12:16.590 Insulinomas are clinically characterized 278 00:12:16.590 --> 00:12:20.370 by attacks of hyperinsulinemia and hypoglycemia. 279 00:12:20.370 --> 00:12:22.020 These tumors are a component 280 00:12:22.020 --> 00:12:25.140 of the Zollinger-Ellison syndrome defined by the triage 281 00:12:25.140 --> 00:12:30.140 of various ulcers, secretion of different enzymes, 282 00:12:31.770 --> 00:12:34.413 and pancreatic islet cell tumors. 283 00:12:36.180 --> 00:12:37.980 Most islet cell tumors are benign 284 00:12:37.980 --> 00:12:40.713 and less than 10% are malignant carcinomas. 285 00:12:43.127 --> 00:12:46.110 Finally, to turn to pancreatic cancer prevention, 286 00:12:46.110 --> 00:12:48.510 unfortunately there are no preventive methods. 287 00:12:48.510 --> 00:12:50.400 In order to reduce risk, 288 00:12:50.400 --> 00:12:52.440 individuals can avoid tobacco and alcohol, 289 00:12:52.440 --> 00:12:54.870 maintain a healthy weight through regular exercise, 290 00:12:54.870 --> 00:12:57.660 eat a diet rich in fruits, vegetables, and whole grains, 291 00:12:57.660 --> 00:13:00.303 and maintain blood glucose within normal limits.