Body mass index and weight gain after middle adulthood are associated with risk of papillary thyroid cancer: A case–control study

1

Introduction

Thyroid cancer is the most common endocrine cancer and its incidence has sharply increased worldwide in recent decades [1] . Most of that increase is accounted for by papillary thyroid cancer (PTC) that comprises 80% of all subtypes of thyroid cancers [2] . In China, the latest data from the Chinese National Cancer Center estimated the nationwide cancer incidence and reported about 201,000 new cases of thyroid cancer in 2015, of whom 50,000 are men and 151,000 are women. The crude incidence rate (CIR) and age-standardized incidence rate (ASIR) are 14.60 per 100,000 and 12.05 per 100,000 population, respectively, and higher in women than in men (CIR 22.56 per 100,000 and ASIR 18.29 per 100,000 population) [3] . Currently, the use of ultrasound and increased screening practices are believed to be part of the cause of the increased incidence of thyroid cancer. However, it is still unclear why the detection of large tumor size and advanced-stage thyroid cancer is increasing simultaneously [45] . In addition to ionizing radiation as a clear risk factor for thyroid cancer, other factors should be inferred as the major population-attributable risk factor(s) because people are unlikely to be frequently exposed to ionizing radiation in everyday life.

In the past 30 years there has been a parallel increase in the incidence of obesity, and the prevalence of obesity has dramatically doubled worldwide [67] . From 1975–2016, the prevalence of obesity among adults increased from 3% to 11% in males and from 6% to 15% in females [8] . Long-term obesity is an acknowledged risk factor for several major cancers [910] . Body mass index (BMI), a major surrogate indicator for obesity, is reportedly associated with six cancers: namely leukemia, multiple myeloma, and pancreatic, endometrial, rectal, and renal-cell carcinoma [11] . Similarly, several epidemiological studies have investigated the association between BMI and thyroid cancer, but the association is controversial. A systematic review and meta-analysis pooled 21 studies which indicated that, compared to the controls with normal weight, the individuals with overweight and obesity had a 25% and 55% greater risk of thyroid cancer, respectively [12] . However, some other studies have shown that the association between BMI and thyroid cancer is weak or even not significant [1113141516 .

Weight change during adulthood directly determines the classification of BMI, because it tends to reflect the accumulation of body fat mass rather than lean mass [17] . In recent years, the impact on human health of weight gain during adulthood has increasingly attracted attention. A large prospective cohort study investigated the effect of weight change after young adulthood (25 years old) on mortality among 36,051 individuals, and the results indicated that weight gain from young to middle adulthood was related to an increased risk of mortality [8] . Furthermore, several studies have suggested that weight gain during adulthood can elevate the risk of cancers such as breast cancer, colorectal cancer, ovarian cancer and male pancreatic cancer 1819202122 . However, the evidence regarding weight change during adulthood and thyroid cancer is limited and inconclusive (see Supplementary Table S1 for a summary of these associations).

In body development, weight will approach peak levels and change relatively slowly in middle adulthood [22] . Weight and BMI gain in adolescence or early adulthood is susceptible to hormonal factors, eating habits, and lifestyle, which largely determine the state of weight and BMI in middle adulthood. Nevertheless, the weight gain subsequent to middle adulthood is more related to unfavorable fat distribution and reduced metabolic efficiency, which also influences weight in later life [23] . In the light of these factors, the issue of whether weight change from middle adulthood is associated with thyroid cancer should be further investigated. Therefore, this study hypothesized that obesity and weight gain after middle adulthood may elevate the risk of PTC. We conducted a matched case–control study involving three hospitals, and collected weight data for each participant at age 35 to approximate the effect of weight change from middle adulthood on PTC.