Advances in genomics, long-term follow-up of atomic bomb survivors, and prevention studies all point to a long course for tumor development. We know that life-style habits are modifiable and that such change translates to reduced cancer risk, but a root question is whether we are intervening early enough in life to achieve benefits. For example, recent genomic studies of pancreatic cancer suggest that the timeline from the first cellular changes that initiate the tumor to the parental clone is 8 to 14 years, from the clone to subclones with metastatic potential 3 to 10 years, and a further 2 to 4 years to diagnosed metastatic disease (which is typically followed by death within a year) (15
). Thus, pancreatic cancers form over 13 to 28 years.
The time course of pancreatic cancer development is similar to that of colon and cervical cancer, confirming that avoidance of early risk accumulation must occur 20 or more years before the projected onset of symptomatic disease. Retrospective case-control studies rarely assess data this long before diagnosis because subject recall is increasingly unreliable with longer times (16
). Even the longest-running prospective studies have almost no data beyond 30 years after the original assessment of putative cancer-causing life-style and environmental factors. Indeed, there are few studies of adolescent and early-adult life-style and cancer risk, and they are lost in the preponderance of evaluations of adult diet, activity, and other risk factors. Thus, most of the available evidence on the causes of cancer is lacking data from the early stages of the relevant time course (17
). Nevertheless, because some life-style behaviors are consistent over time, we can still glean some information about cancer prevention from the studies that have been done to date.
We know that behavioral changes and interventions early in the lives of young women reduce breast and cervical cancer, because these cancers develop over years and decades (). Physical activity, vaccination for viruses, and minimizing sun exposure are most effective when begun early in life, for young men as well as for young women.
More physical activity in women from the onset of menarche throughout the premenopausal years can reduce the risk of breast cancer by at least 25% (18
). In contrast, alcohol intake (a known breast cancer carcinogen) during adolescence significantly increases the risk of benign breast disease, a precursor of breast cancer (19
), while fiber intake during adolescence may substantially reduce breast cancer risk (20
). These results mean that recent reductions to or elimination of school physical education and sport programs may increase breast cancer incidence, an effect that may not be evident for decades to come. This example illustrates why a younger, broader population than is typically considered to be at risk for cancer must be engaged to effect meaningful prevention.
Another environmental factor that can be modified early in life to prevent later cancers is infectious disease. Cancer resulting from infection accounts for ~5% of all cancer cases in the United States and in most established market economies; in low- and middle-income countries, these cancers account for a substantially larger percentage of the total. Cancer-causing infections with HPV (cervix), Helicobacter pylori
(stomach), and hepatitis B and C (liver) together account for 18% of the global cancer burden (21
). Already, vaccination against hepatitis has reduced liver cancer incidence by 70%, 20 years after initiation of the vaccination program, although protection into later adult life remains to be documented (22
) (). Modeling indicates that HPV vaccination programs can reduce incidence of cervical cancer by 50 to 70%, depending on the level of vaccine coverage in the population (23
Sun exposure also initiates cancer-promoting damage early in life. The sun, as the primary source of ultraviolet (UV) radiation, poses a significant risk of skin cancer, particularly but not exclusively in fair-skinned Caucasians. The U.S. National Cancer Institute (NCI) estimates that there will be 70,230 new cases in 2011 in the United States and, without prevention, this number will only increase as the protective ozone layer recedes. Prevention recommendations as simple as avoiding the sun in peak hours (10 a.m. to 3 p.m.), covering the skin whenever possible, protecting exposed skin with sunscreen, and avoiding tanning booths are effective in reducing skin cancer incidence, particularly if these life-style changes are adopted at an early age.
The effectiveness of prevention efforts such as those described above has been well documented. The CDC Task Force on Community Preventive Services concluded that school-based educational and policy interventions (for children) and recreational-based educational and policy interventions (for adults) were effective in reducing sun exposure (24
). Community-scale urban design and land use policies, as well as street-scale design, may promote physical activity (25
) Both types of intervention are exemplified by the Australian SunSmart (formerly Slip! Slop! Slap!) program, ongoing since 1982, which aims to reduce UV exposure through access to shade and consistent use of protective clothing, hats, sunglasses, and sunscreen (26
). SunSmart efforts include formal accreditation of schools that adhere to its policy and practice requirements and collaboration with governmental agencies to protect outdoor workers.
SunSmart can be credited with successfully changing attitudes regarding sun tanning, increases in protective behavior, decreased costs of sun protection gear, societal acceptance of more protective attire (including hats, sunglasses, and neck-to-knee swimsuits for children), and, most important, decreasing incidence rates of skin cancer (26
). The evidence from Australia indicates that active prevention efforts, including television advertising campaigns, can be highly effective in improving the population-wide sun-protective behaviors (27
), resulting in falling age-specific incidence rates for melanoma in younger birth cohorts (28
). In contrast, the United States fails even to enforce policies limiting preadolescent and adolescent tanning bed use (29
Our now clear understanding of the years- to decades-long time frame of tumor development, which often starts early in life, should propel us to think anew about how we can organize and commit resources to markedly reduce the burden of cancer on individuals and society.