Fight Aging!

Today's research materials discuss an interesting aspect of cancer epidemiology. Cancer survivors exhibit a greater risk of developing later primary cancers, unconnected to the prior cancer, and in addition suffer a greater mortality than first time cancer patients with those same cancer types. There are a number of possible explanations for this data, two of which are noted below. The data leans strongly towards the first of the two.

Firstly, cancer risk is driven by specific mechanisms of aging: a faltering immune system, unable to stop cancers in their earliest stages by killing precancerous cells efficiently enough; greater chronic inflammation, spurring faster growth of cancerous tissue; greater levels of DNA damage and clonal expansion of mutations throughout tissue. People who have cancer will, on balance, be more damaged and more aged than those who do not have cancer. Thus they will continue to have a higher risk in the future. Picking people who have already survived cancer is a way of selecting for individuals who have, on average, a greater burden of age-related damage and other pro-cancer mechanisms and circumstances, such as obesity or a smoking habit.

Secondly, the treatment of cancer is inherently damaging in and of itself. The most commonly used cancer therapies, chemotherapy and radiotherapy, produce a sizable increase in the number of lingering senescent cells in the body as a side-effect of killing cancerous tissues. Stressed, damaged cells that do not die will become senescent, and the aged immune system present in most cancer patients will not efficiently destroy those senescent cells. Senescent cells secrete an inflammatory, pro-growth mix of signals that makes future cancers that much more likely, and indeed accelerate progression of all of the other aspects of aging as well. Surviving chemotherapy is about as bad for your long-term health as a robust smoking habit, when looking at the mortality data.

Study finds cancer survivors run greater risk of developing, dying from second cancers

A new study finds that adult-onset cancer survivors run a greater risk of developing and dying from subsequent primary cancers (SPCs) than the general population. Cancers associated with smoking or obesity comprised a majority of SPC incidence and mortality among all survivors. For the study, investigators analyzed data on nearly 1.54 million cancer survivors from 1992 to 2017 from 12 Surveillance, Epidemiology, and End Results registries in the United States. The findings suggest that among the 1,537,101 survivors, 156,442 were diagnosed with an SPC and 88,818 died of an SPC. Results found that male survivors had an 11% higher risk of developing SPCs and a 45% higher risk of dying from SPCs compared with the risk in the general population. Female survivors had a 10% higher risk of developing SPCs and a 33% higher risk of dying from SPCs.

Results show the risks of smoking-related SPCs were commonly elevated among survivors of smoking-related first cancers. Among survivors of all cancers, four common smoking-related SPCs including lung, urinary bladder, oral cavity/pharynx, and esophagus, accounted for 26% to 45% of the total SPC incidence and mortality. Furthermore, lung cancer alone comprised 31% to 33% of the total mortality from SPCs. Similarly, survivors of many obesity-related cancers had an elevated risk of developing obesity-related SPCs. Among survivors of all cancers, four common obesity-related cancers colorectum, pancreas, corpus uteri, and liver, comprised 22% to 26% of total SPC mortality.

Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States

The objective of this study is to quantify the overall and cancer type-specific risks of subsequent primary cancers (SPCs) among adult-onset cancer survivors by first primary cancer (FPC) types and sex. Among 1,537,101 survivors (mean age, 60.4 years; 48.8% women), 156,442 SPC cases and 88,818 SPC deaths occurred during 11,197,890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population.

The highest overall standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were estimated among survivors of laryngeal cancer (SIR, 1.75; incidence, 373 per 10,000 person-years) and gallbladder cancer (SMR, 3.82; mortality, 341 per 10,000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48; incidence, 336 per 10,000 person-years; SMR, 4.56; mortality, 268 per 10,000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs.

Among survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.