A Quick Guide to Cancer Epidemiology

“Neoplasms include several hundreds of diseases, which can be distinguished by localization, morphology, clinical behaviour and response to therapy. […] Malignant neoplasms are characterized by progressive growth of tissue with structural and functional alterations with respect to the normal tissue. In some cases, the alterations can be so important that it becomes difficult to identify the tissue of origin. A peculiarity of most malignant tumours is the ability to migrate and colonize other organs (metastatization) via blood and lymph vessel penetration. The presence and extension of metastases are often the critical factors to determine the success of therapy and the survival of cancer patients. The pace of growth of malignant neoplasms varies widely, and asymptomatic neoplasms are often found at autopsy of individuals deceased from other causes. […] Most malignant neoplasms (about 90 %) in adults arise from epithelial tissues and are defined as carcinomas. […] Knowledge about the causes and the possible preventive strategies for malignant neoplasms has greatly advanced during the last decades. This has been largely based on the development of cancer epidemiology.”

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I finished this book yesterday. I complained in my coverage of Managing Cardiovascular Complications in Diabetes that that book was full of formatting errors and that it seemed that nobody had proofread the book before publication, and I said in that post that ‘It’s much rarer, I think, to see stuff like that in Springer publications.’ I might be wrong about this, or at least I’ve updated my priors on that one; this specific book was even worse than the Managing Cardiovascular complications book in that respect – errors are all over the place. It’s odd and also slightly annoying, because if not for that problem I would consider this book to be a really nice little resource.

The book deals mainly with the data, and it is not a methodology text. Occasionally how we know what we know is important and the limits of our knowledge is important, so methodological questions are addressed here and there; but you certainly don’t need to have read a book like this to understand it, and although many specific details in the book presumably would not be understood by a random guy who’d just finished high school, most of the book is relatively easy to follow. This disease is this common in this area and that common in that area and the difference between these two areas may be due to these things; it kills this many people; these are some of the risk factors we know about, and the role they play is this – most of the book deals with questions such as these, and there are only so many ways you can make stuff like that impossible to understand by using a lot of fancy medical terms.

The book provides an excellent overview and the data and the level of coverage is actually quite excellent considering the length of the book – if not for the many errors and general sloppiness I’d feel tempted to give it a high rating. We know more than I thought we knew about these things, which is nice, and a few of the observations included were surprising to me. Of course a lot of details are missing but this is to be expected – people have written books about topics covered in a few pages here (e.g. this). If you read Mukherjee and this book, I think you’ll be off to a great start in terms of understanding cancer better; the obvious next step would be a book like this, but most people are probably not going to read stuff like that.

I should point out that perhaps I was a bit too hard on the lecture about the UK million women study in the recent Open Thread – I find it important to note in particular that specific topics also covered in this book, such as the role of birth control and hormone replacement therapy in cancer development, are covered in more detail in that lecture than they are in this book; so I refer you to that lecture, rather than covering that stuff below. Some of this stuff is the sort of stuff I’d probably want to know about if I were of the opposite gender. I should point out as well here that one of the reasons I did not think too highly of her lecture relates to her comments about cancer screening during the lecture (I think it’s around the 35 minute mark or so). Those comments annoyed me because I think she’s being intellectually dishonest during her lecture by not addressing the main problems with the pro-screening position, but only presents a weaker argument (to an audience unlikely to know any better) which is much easier to knock down – in the context of breast cancer screening the main argument against them, from what I’ve gathered, is not that these things do not save any lives (though there’s also a lively debate about how many lives are actually saved and how you should go about estimating this number), but rather that the costs – both monetary and non-monetary (the latter e.g. relating to the mental anguish experienced by the many, many women who get a false positive test result) – are not justified; there’s much more about these and related things in this book. In general it’s safe to say that it’s quite a bit harder to ‘properly justify’ screening programmes than many doctors often seem to think it is. Anyway the book doesn’t go into much detail about these things, and you’ll have to look elsewhere (e.g. Juth and Munthe) for detailed coverage of stuff like that.

I have added some observations from the book below and a few comments.

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“Analytical studies (case–control and cohort) have shown the causal role of specific exposures in the aetiology of several malignant neoplasms. One limitation of the epidemiological approach, which may prove of critical importance in trying to detect comparatively small increases in risk, as in the case of environmental pollutants, is that even in the best conditions it is impossible to confidently identify by epidemiological means an increase in risk smaller than say 10–20 % (and serious problems arise in the interpretation of increases below 50 %), as the biases inherent in any observational study are of at least this order of magnitude (Adami et al. 2008).”

“In addition to lead-time bias, three types of bias are peculiar to the assessment of screening programmes. Because of self-selection, persons who elect to receive early detection may be different from those who do not: for instance, they may belong to better educated classes, be generally healthier and health conscious, and this could produce a longer survival independent of any effect of early detection. In addition, cancers with longer pre-clinical phases, which may mean less biological aggressiveness and better prognosis, are, in any case, more likely to be intercepted by a programme of periodical screening than cancers with a short pre-clinical phase, and a rapid, aggressive clinical course (length bias). Finally, because of criteria of positivity adopted to maximize yield of early cases, a number of lesions which in fact would never become malignant growths are included as ‘cases’, thus falsely improve the survival statistics (over-diagnosis bias).”

“The number of new cases of cancer which occurred worldwide in 2008 has been estimated at about 12,700,000 […]. Of these, 6,600,000 occurred in men and 6,000,000 in women. About 5,600,000 cases occurred in high-resource countries (North America, Japan, Europe including Russia, Australia and New Zealand) and 7,100,000 in low- and medium-resource countries. Among men, lung, stomach, colorectal, prostate and liver cancers are the most common malignant neoplasms […], while breast, colorectal, cervical, lung and stomach are the most common neoplasms among women […] The number of deaths from cancer was estimated at about 7,600,000 in 2008 […] No global estimates of survival from cancer are available: data from selected cancer registries suggest wide disparities between high- and low-resource countries for neoplasms with effective but expensive treatment, such as leukaemia, while the gap is narrow for neoplasms without an effective therapy, such as lung cancer […] The overall 5-year survival of cases diagnosed during 1995–1999 in 23 European countries was 49.6 % (Sant et al. 2009).”

“Survival from breast cancer has slowly increased in high-resource countries, where it now achieves 85 %, following improvements in screening practices and treatments. Survival in low-resource countries remains poor, in the order of 50–60 %. Breast cancer is the most common cancer among women worldwide: the estimated number of new cases in 2012 was 1,680,000” [I had no idea survival rates were that high in ‘high-resource countries’, though it’s a bit problematic that it is not spelled out what is actually meant by ‘survival’; I gather from this link that it’s the 5-year survival rate.]

“Tobacco smoking is the main single cause of human cancer worldwide (IARC 2004) and the largest cause of death and disease. It is the key cause of lung cancer, and a major cause of cancers of the oral cavity, pharynx, nasal cavity, larynx, oesophagus, stomach, pancreas, uterine cervix, kidney and bladder, as well as of myeloid leukemia. In high-resource countries, tobacco smoking causes approximately 30 % of all human cancers (Doll and Peto 2005). […] A benefit of quitting tobacco smoking in adulthood has been shown for all major cancers causally associated with the habit. Smokers who stop around age 50 avoid over 50 % of overall excess mortality from all causes (Doll et al. 2004; Jha et al. 2013; Pirie et al. 2013), from lung cancers (Peto et al. 2000) and well as from other tobacco-related cancers (Bosetti et al. 2008a), and those who stop around age 40 or earlier avoid most of their tobacco-related cancer risk. […] “The risk of lung cancer among smokers relative to the risk among never-smokers is in the order of over 20-fold […] In the UK million women study, the RRs [relative risks] of lung cancer were 10.5 for current smokers of 10 cigarettes per day, 22.0 for 15, and 36.0 for ≥20 cigarettes per day. […] An association has been shown in many studies between exposure to involuntary smoking and lung cancer risk in non-smokers. The magnitude of the excess risk among non-smokers exposed to involuntary smoking is in the order 20 % (IARC 2004).” [You have a 20% risk increase from passive smoking and a twenty-fold increase from smoking. My conclusion from these observations would be that in terms of cancer risk passive smoking doesn’t really matter in the big picture, and that it is overhyped as a disease risk factor – the excess cancer risk attributable to smoking probably causes more than 100 cancers in smokers for each cancer case in a non-smoker, and most of the non-smokers who develop cancerous lesions will have been exposing themselves for years – questioning the assumption that they did not willingly take on this risk]. Lung cancer is “the most important cause of cancer death worldwide. It accounts for an estimated 1,250,000 new cases and 1,100,000 deaths each year among men and 580,000 cases and 500,000 deaths among women […]. Survival from lung cancer is poor (around 10 % at 5 years).”

“The role of dietary factors in causing human cancer remains largely obscure. For no dietary factor other than alcohol […] and aflatoxin (a carcinogen produced by some fungi in certain tropical areas) there is sufficient evidence of an increased or decreased risk of cancer. […] Alcohol drinking increases the risk of cancers of the oral cavity, pharynx, larynx, oesophagus and liver, colorectum and female breast (Baan et al. 2007). For all cancer sites, risk is a function of the amount of alcohol consumed […] The global burden of cancer attributable to alcohol drinking has been estimated at 3.6 and 3.5 % of cancer deaths (Boffetta 2006), although this figure is higher in high-resource countries (e.g., the figure of 6 % has been proposed for United Kingdom (Doll and Peto 2005) , and 9 % in Central and Eastern Europe). These included over 5 % of cancers and cancer deaths in men and about 1.5 % of cancers and cancer deaths in women. […] Systematic reviews have concluded that nutritional factors may be responsible for about one-fourth of human cancers in high-resource countries, although, because of the limitations of the current understanding of the precise role of diet in human cancer, the proportion of cancers known to be avoidable in practicable ways is much smaller (Doll and Peto 2005). The only justified dietary recommendation for cancer prevention is to reduce total caloric intake, which would contribute to a decrease in obesity, an established risk factor for human cancer […] There is sufficient evidence for a cancer preventive effect of avoidance of weight gain, based on a decreased risk of cancers of the colon, gallbladder, post- menopausal breast, endometrium, kidney and esophagus (adenocarcinoma) […] Estimates of the proportion of cancers attributable to overweight and obesity in Europe range from 2 % (Doll and Peto 2005) to 5 % (Bergstrom et al. 2001).”

“There is growing evidence that chronic infection with some viruses, bacteria and parasites represents a major risk factor for human cancer, in particular in low-income countries […] The population attributable fraction for infectious agents was 16.1 % in 2008, meaning that around two million new cancer cases were attributable to infections. HBV and HCV-related liver cancer, HPV-related cervical cancer and Helicobacter pylori-related stomach cancer overall are responsible for 95 % of the total number of infection-related cancers. The estimate of the attributable fraction is higher in less developed countries than in high-resource countries (22.9 % of total cancer versus 7.4 %). […] Cervical cancer is a major public health problem in many low and middle income countries. Incidence rates are high (20–40/100,000) in sub-Saharan Africa and Latin America countries, as well as in India and southern Asia. […] Chronic infection with HPV is a necessary cause of cervical cancer. Using sensitive molecular techniques, virtually all tumours are positive for the virus […]. Different types of HPV exist, and those associated with cervical cancer are mainly types 16, 18, 31, 45 and 58. In particular, HPV 16 is the main cervical carcinogen in most populations”.

“Approximately 40 occupational agents, groups of agents and mixtures have been classified as carcinogenic by IARC […] Estimates of the global burden of cancer attributable to occupation in high-income countries result in figures in the order of 1–5 % (Doll and Peto 2005 ; Schottenfeld et al. 2013). In the past, almost 50 % of these were due to asbestos alone, while in recent years the impact of asbestos on lung cancer […] is levelling off […] However, these cancers concentrate in some sectors of the population (mainly male blue-collar workers), among whom they may represent a sizable proportion of total cancers […] The available evidence suggests, in most populations, a small role of air, water, and soil pollutants. Global estimates are in the order of 1 % or less of total cancers (Doll and Peto 2005; Schottenfeld et al. 2013). This is in striking contrast with public perception, which often identifies pollution as a major cause of human cancer. However, in selected areas (e.g., residence near asbestos processing plants or in areas with drinking water contaminated by arsenic), environmental exposure to carcinogens may represent an important cancer hazard.”

“No precise estimates are available for the global contribution of drug use to human cancer. It is unlikely, however, that they represent more than 1 % in high-resource countries (Doll and Peto 2005). Furthermore, the benefits of therapies are usually much greater than the potential cancer risk.”

“A number of inherited mutations of a high-penetrance cancer gene increase dramatically the risk of some neoplasms. However, these are rare conditions in most populations and the number of cases attributable to them is rather small.” [An example: “breast cancer risk is greatly increased in carriers of mutations of several high-penetrance genes, in particular BRCA1, BRCA2, ATM, CHECK2 and p53. Although the cumulative lifetime risk in carriers of these genes is over 50 %, they are rare in most populations and explain only a small fraction (2–5 %) of total cases.”]