Childhood overweight and pubertal timing as predictors of adult cancer in men

Background and Aim Obesity is one of the leading causes of cancer globally. The importance of overweight in childhood for adult cancer risk, independent of overweight status in young adulthood is still unknown. Furthermore, how male pubertal timing influences the risk of prostate cancer has not been established. Birthweight has been associated with increased cancer risk. Short term trends of increasing birthweights are established, but trends from before the initiation of the obesity epidemic are scarce. The aims of this thesis were to evaluate the importance of high body mass index (BMI) in childhood, independent of the subsequent BMI development during puberty, for colon and rectal cancer, hematologic malignancies and obesity-related cancer in late adulthood. Further, we also sought to explore a possible link between pubertal timing and prostate cancer, and to characterize the long-term trends of birthweight in boys before and during the obesity epidemic. Methods Projects I-IV used a cohort of men born 1945-61 who finished school in Gothenburg. Height and weight measurements were collected from School Health Care records and military conscription tests. The main exposure variables were body mass index (BMI) at 8 and 20 years of age, pubertal BMI change (the difference in BMI between 8 and 20 years of age), and age at peak height velocity (PHV), an objective marker of pubertal timing. Cancer outcomes were collected from national registers. In project V, we assessed the long-term birth weight trends of 46.548 boys born between 1946 and 2011. Results Overweight at age 8 associated with an almost tripled risk of colon cancer (HR 2.81, 95% CI 1.70-4.64) compared to normal weight at 8 years, when both groups had a pubertal BMI change above the median (Paper I). For hematological malignancies, BMI at 8 years was significantly associated with increased risk of overall hematologic malignancy, and with increased risk of Non-Hodgkin Lymphoma (HR 1.14, 95% CI 1.00-1.30), but increased height at age 8 was linked to a higher risk of multiple myeloma (HR 1.31, 95% CI 1.03-1.67) (Paper II). Boys with childhood overweight that normalized during puberty, but not boys with pubertal onset overweight, had substantially increased risk of obesity-related adult cancer (HR 1.38, 95% CI 1.04-1.78) compared with those with a normal body weight at both 8 and 20 years of age (Paper III). We found a reduced risk of prostate cancer, and high-risk prostate cancer for individuals with late pubertal timing (HR 0.73 for Q5 vs Q2-4, 95% CI 0.54-0.96) (Paper IV). For birthweight trends, three significant periodic fluctuations were identified; a decrease between 1950–1980, an increase between 1980–2000, and finally another decrease between 2000–2010, but the overall birthweight trends between 1950-2010 were stable. Conclusions These findings establish that onset of overweight in childhood is of specific importance for adult cancer development in men, and demonstrate a reduced risk of prostate cancer and the clinically important high-risk or metastatic prostate cancer in individuals with late pubertal timing. The long-term birth weight trends are marginal and future studies should determine the associations between birthweight and cancer risk independent of childhood overweight

Timing of the pubertal growth spurt and prostate cancer

Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids