Monday, April 26, 2010

Childhood and Adolescent Exposures Set Cancer Risk

At the annual meeting of the American Association for Cancer Research (AACR), I presented a review of evidence relating childhood and adolescent exposures to lifetime cancer risk (see slides from presentation here One of many “meet the expert” sessions, this offered an opportunity for those in the audience to hear a synthesis of evidence on the importance of this time period and the value of considering where in the life course exposures may be most important for determining cancer risk.

The most compelling evidence that early exposure drives risk of cancer throughout life comes from the follow-up of the atomic bomb survivors in Japan (Land et al., 2003). For some 70,000 survivors, researchers calculated their exposure to radiation based on where they were located at the time of bomb explosion. During 40 years of follow-up cases of breast cancer were identified. Women exposed before age 20 had substantially higher risk for breast cancer through their adult life than those who were older when exposed. Another established example is the development of moles in response to sun exposure, as well as sun burns during adolescence, driving lifetime risk of melanoma. I next turned to smoking and lung cancer as another common piece of evidence in the puzzle of cancer risk accumulation. Importantly, with Stacey Kenfield and colleagues we had assessed age at starting to smoke and  the risk of lung cancer (Kenfield et al., Tobacco Control 2008). We showed that for each year earlier that an adolescent starts to smoke the risk of lung cancer increases by 5 percent. Given that the majority of smokers have become regular smokers by age 18 this shows the importance of late childhood and adolescence for susceptibility to the effects of carcinogens in tobacco smoke.

The strong and consistent relation between adult height and cancer risk points directly to the exposures during growth and development that account for increasing height in populations as children grow up in industrialized settings. A study of over 400,000 men and 300,000 women in Korea who were measured for height and weight in the mid 1990s and followed for 10 years showed that total cancer incidence rose steadily with height (Sung et al., Am J Epidemiol 2009). For each 5 cm (approximately 2 inches) increase in height, the risk of cancer rose by 5 percent in men and women. Over 300 studies have assessed this general relation and consistently show that height is related to cancers of the breast, prostate, colon, and endometrium, as well as to hematologic malignancies.

Height reflects the end result of growth through childhood. Increasing height over decades or generations reflects improved diet and access to abundant sources of energy intake, reduction in childhood infections and changes in the environment that impact physical activity and energy expenditure. The growth spurt of early adolescence also has an impact on risk. The more a young adolescent woman grows in a year the higher her lifetime risk of breast cancer (Berkey et al, Cancer 1999). No doubt, as the speed of growth increases the stress on cell mechanisms to repair errors in cell division is increased. 

I next reviewed other factors that may influence height including diet. Drawing on the data from the Growing Up Today Study, which I initiated back in 1996, I showed data relating milk intake to height in girls (Berkey et al., Cancer Epidemiology Biomarkers and Prevention 2009). Those who consumed more than 3 glasses of milk per day grew taller in the next year than those consuming less than a glass per day. One likely explanation for this added growth is hormonal exposures. A feeding trial shows that after consuming milk regularly for a month, insulin-like growth hormone levels are higher (Rich Edwards et al., 2007).

Drawing on data for breast cancer, I showed that age at menarche, the onset of menstrual periods in a young woman, has been younger since the industrial revolution. In the 1850 and 60s the average age for menarche was about 17. In Korea at the time of the second war this was still the average age at menarche. In Europe over 100 years the average age for menarche has dropped to about 13, but in Korea this drop happened in just 20 years after World War II (see figures in slides). For generations of women born after WWII in Korea the incidence of breast cancer breast cancer at age 45 to 49 has doubled in just 10 years and is expected to continue increasing. A drop in the number of children each women is having from an average of 6 to only about 1 child per women has added to this increase in risk within the population.

Adolescent diet and risk.
Given the importance of growth on age at menarche and height, we have explored the possibility that diet during adolescence may modify the subsequent risk for beast cancer. We had participants in the Nurses Health Study II recall their diet in high school. We then followed them over time and identified women who went on to develop benign breast disease and those who remained free from disease. Benign breast disease is a well established marker of subsequent risk of breast cancer. Changes in benign lesions follow a pattern of increasing lack of order until the lesions progress to invasive breast cancer over many decades. We showed that higher intake of fiber in adolescence significantly reduced the risk of benign breast disease (see related post In another study we showed that alcohol intake during late teen years and the early 20s more than doubled a young women’s risk of benign breast disease ( In a study of women in Hawaii, Anna Wu and colleagues showed that intake of soy during childhood was most protective against breast cancer risk.

Turning to exercise, several studies now show that sustained activity from menarche through adult years brings the greatest reduction in breast cancer risk (see Maruti et al JNCI 2008). Higher activity can cut breast cancer risk by anywhere from a quarter to a half. Thus growing evidence points to childhood and adolescence as a key period in life when the trajectory for cancer risk is determined in part by diet and exercise patterns.

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