Cancer incidence in urban Shanghai, 1973-2010: an updated trend and age-period-cohort effects

This study provided a comprehensive and up-to-date overview of temporal trends and the age-period-cohort effects on cancer incidence in urban Shanghai over the past four decades. Regarding trends for all cancers combined, the incidence declined slightly and significantly in males during the whole period of 1973–2010, but a statistically significantly increased trend was noted in females. During the most recent 10 years (2001–2010), the overall cancer incidence rates in males decreased by 1.65 % per year, but stabilized in females. The results showed that the trends and change points for incidence trends varied by cancer sites, and the age, period and birth cohort also yielded different effects by cancer types. The trend patterns could be predicted by both time periods of diagnosis and birth cohort components. The cancer types which were common among males and females had similar trends and the trends had no significant difference according to EAPC values, except for lung cancer.

Scrutiny of trends in cancer incidence can help to recognize trends related to changes in cancer risk, including risks mediated by exposures to environmental and occupational carcinogens. With its diversity as an asset, Shanghai has enjoyed remarkable economic growth in the last four decades, experiencing rapid changes in population aging, urbanization, and social transformation, which could bring great impact on cancer patterns and variation of temporal trends. The particular tumors selected that may be influenced by these changes were discussed below.

Esophagus and stomach cancers showed a remarkable and steady decrease in incidence over the study period, and the trends were also reflected in the gradual decline in risk in successive generation among both sexes born approximately after 1900. The decrease in esophageal and stomach cancer rates in both males and females can be expected to continue in consideration of the sharp decline in younger birth cohorts. The patterns were likely to be attributable to the general improvements in living conditions in Shanghai, such as increasing consumption of fresh fruit and vegetables, the widespread use of refrigeration, and decreasing intake of salt-preserved food and beverage at high temperatures [5, 16]. Other possible determinants for the favorable trends of stomach cancer were reductions in infection of Helicobacter pylori because of improvements in socioeconomic status and sanitary conditions of housing [5].

Colorectal cancer was one of the most rapidly increasing malignancies and it was the second most frequent cancer in urban Shanghai. Previous studies have suggested that maintenance of a healthy diet and avoidance of a sedentary lifestyle and obesity may reduce the risk of colorectal cancer [17]. It thus appeared that the changes in lifestyles, such as less physical activity, and excess weight, may contribute to the persistently rising rates in urban Shanghai [18, 19]. In the US, continuous decline in colorectal cancer incidence in recent years was most likely attributable to significant improvements in the use of colorectal cancer screening [20]. A local colorectal cancer screening program using biennial fecal occult blood testing (FOBT), followed by total colonoscopy in positive patients, has been implemented in Shanghai since 2012, and this program will influence its incidence trend in future.

Incidence from liver cancer was favorable for both sexes over the whole period and the declines in risk have been observed among successive birth cohorts born since 1915s in urban Shanghai. Etiological determinants of liver cancer include chronic infection with hepatitis B virus (HBV), and exposure to dietary aflatoxin, alcohol consumption and smoking [21, 22], all of which may partially contribute to the decreasing trend. Measures to prevent HBV infection by managing blood and its products, and measures to ensure an improved water quality by purifying polluted water source, have largely decreased the risk of HBV infection and aflatoxin B1, respectively [23]. Other measures such as attempts to reduce the consumption of smoking and heavy drinking, and a focus on a balanced diet [24, 25] may also be attributed to the risk downward of liver cancer. The newborns in urban Shanghai have been inoculated with the HBV vaccine under the aggressive vaccination program since 1992 [25], so further decreased incidence will be seen in these children as they become adults about 10–30 decades later [26]. It should be noted that liver cancer incidence rates were increasing in many parts of the world including the US and Central Europe, possibly due to the obesity epidemic and the rise in hepatitis C virus (HCV) infection [27].

The incidence of pancreas cancer in urban Shanghai has increased constantly since the 1970s, which is consistent with the increasing rates among successive birth cohorts. Factors that contributed to the increasing rates in males and females were not fully elucidated. Limited studies showed that improvement in the diagnosis of pancreas cancer and changes in lifestyles (such as changing of dietary patterns and increasing prevalence of obesity) may partly explain the rising trend [28‐31].

This study was the first to document a significant slight decrease in lung cancer incidence among males during the observed period in urban Shanghai, with accompanying more substantial decline in the most recent 10 years, a changing from a plateau to a gradual reduction. Similarly, although the incidence was relatively stable in females over the whole period, an encouraging trend after 2001 was observed. APC models also suggested that incidence rates began to decline for younger generations born around 1960. Therefore, the decreases in lung cancer rates in both males and females can be expected to continue with lower risk of younger birth cohorts. Overwhelming majority of lung cancer was caused by tobacco smoking, accounting for 80 % of the worldwide lung cancer burden in males and at least 50 % of the burden in females [27]. The prevalence of smoking among males tripled in China from the early 1950s to the late 1980s and reached 61 % in Shanghai during 1970s [5]. The smoking prevalence in Shanghai showed signs of stability or slight decreasing since 1970s and estimated as 55.37 % among males and 1.47 % among females aged 15 and above in 2010 [32]. Lung cancer risk among women in urban Shanghai was linked to smoking, as well as to exposure to rapeseed oil vapors during high-temperature cooking [33]. The downward trend observed in female lung cancer incidence in recent 10 years reflected the improvements in kitchen ventilation and in living conditions. The risk of lung cancer from cigarette consumption among males in Shanghai may have been attenuated by some protective factors such as intake of certain fruits and vegetables and by improvements in the work environment [5, 34].

Female breast cancer has increased substantially in urban Shanghai, becoming the leading cancer among females in the late 1980s. Population-based breast cancer screening programs with effective tools such as mammography and ultrasonography have yet to be implemented in Shanghai. This substantial increase trend in urban Shanghai was driven by cohort effects. Menstrual and reproductive factors, such as early age at menarche, late age at first pregnancy, lack of lactation, and decreasing number of children because of one-child-per-family policy, may partially explain the increasing trend of breast cancer [4, 35]. Other factors including changes in lifestyles, such as high consumption of animal foods and fat, less physical activity, and obesity, may be related to the rising incidence [16, 36]. In contrast, the burden of cervical cancer substantially decreased over time. Strong period and cohort effects were observed in its trend. The dramatic decline in cervix cancer before 1996 could be largely attributed to the widespread Pap smear screening and treatment programs first implemented in Shanghai during the late 1950s [5, 37]. Notably, there appeared a rising trend since 1996. Higher prevalence of Human Papilloma virus (HPV), and changes in lifestyles and sexual behaviors can be partially attributed to the rising risk among younger generations [38].

During the past four decades in urban Shanghai, prostate cancer incidence rates have increased substantially. The incidence rate was among the lowest in the world at 1970s and it became the fifth most common cancer in males after 2002. APC analysis showed that cohort effect increased steadily after the year corresponding to the minimum risk value, whereas period effect seemed to remain unchanged throughout the years. There has been no national or local prostate cancer screening in Shanghai and the reasons for the upward trend may suggest a role of environmental factors and/or increased detection of the tumors based on improved technology and surveillance [4].

Thyroid cancer incidence decreased through the early 1980s, then increased thereafter. The results from APC modeling showed that both period and birth cohort effects appeared to have an impact on the observed incidence trends. The downward during the beginning 10 years may be explained in part by the mass screening conducted in several factories in the mid-1970s, which detected large numbers of occult cancer cases in that period [4]. The improvement in diagnostic modalities and increased medical detection of small thyroid nodules may contribute to the unusual increase in the incidence during the last two decades in both sexes. However, the effects of iodine supplementation and some birth cohort-related changes in environmental exposures (such as increased exposure to diagnostic X-rays) cannot be ruled out for the observed increased risk of thyroid cancer among young birth cohorts. Same patterns in incidence of thyroid cancer were found in the US and Denmark [39, 40]. Further detailed analysis based on histopathology is needed to clarify the potential contributors for the sharp upward of incidence.

Over the study period, the incidence of kidney & renal pelvis cancer had risen rapidly since the 1970s. Accumulating evidences have suggested an etiologic role in renal cell carcinoma for physical activity, alcohol consumption, and occupational exposure to trichloroethylene [41]. Among malignancies of the hematopoietic system, a steady increase in incidence was observed for NHL. No clear understanding of the risk factors can explain the long-term trends. Increasing exposure to one or more ubiquitous lymphomagenic agents [42] such as pesticides may partly contribute to the upward in incidence. Further researches are warranted to clarify the potential risk factors for these cancers with increasing incidence in urban Shanghai.

There were no substantial changes in the registry operation occurred over the study period. It was plausible that at least part of the observed trends on cancer incidence may reflect changes in the prevalence of risk factors and the measures taken for cancer prevention and control in the population. The incidence trends for all cancers combined for males and females varied. The significant download trend in males may be partly explained by the declines in several cancer rates, including esophagus, stomach, liver, and lung cancer, while the increased incidence of colorectum, breast, and thyroid cancers could be partly attributed to the upward trend in females.