|Year : 2017 | Volume
| Issue : 4 | Page : 673-677
Gallbladder cancer incidence in Delhi urban: A 25-year trend analysis
Rajeev Kumar Malhotra1, Nalliah Manoharan1, NK Shukla2, Gourva Kishore Rath3
1 Delhi Cancer Registry, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
2 Department of Surgical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiation Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||30-Jul-2018|
Dr. Rajeev Kumar Malhotra
Delhi Cancer Registry, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Gallbladder cancer (GBC) falls into the top ten leading cancer sites in urban Delhi. The incidence of GBC in females is more than that among males worldwide. The present study evaluates the temporal variation of GBC incidence in an urban Delhi population. MATERIALS AND METHODS: The 25-year GBC incidence data were obtained from Population-Based Cancer Registry (PBCR) of Delhi which covered nearly 97.5% of the population and 75% of Delhi. We applied joinpoint regression method to determine the trend of GBC incidence from 1988 to 2012. The estimated cumulative risk (0–74) and lifetime risk of developing GBC were also calculated. RESULTS: GBC contributed 6% of total cancer cases in Delhi during the year 2012. In the past 25 years, 12,410 GBC cases (4010 males and 8400 females) were registered and contributed approximately 3% of male cancer cases and 6.5% of female cancer cases. The median age at diagnosis of GBC was 60.13 years and 57.22 years in males and females, respectively. Joinpoint analysis showed an overall increasing trend of age-adjusted rates of GBC incidence over 25 years. In females, a downward trend was observed during 1992–2004, whereas in males, the trend remained consistent during 1991–2005; however, thereafter, it started significant increasing for both the genders. Age-specific trend of GBC also reflects an increasing trend among males and females after 2004. CONCLUSION: The total and age-specific GBC cases have show an increasing trend in the past 25 years in urban Delhi. Stringent steps are required to control the modifiable risk factors for reducing the incidence of GBC in Delhi. In addition, individuals should also practice a healthy lifestyle to reduce the likelihood of GBC as well as other diseases.
Keywords: Age-adjusted-rate, cancer, incidence, trend
|How to cite this article:|
Malhotra RK, Manoharan N, Shukla N K, Rath GK. Gallbladder cancer incidence in Delhi urban: A 25-year trend analysis. Indian J Cancer 2017;54:673-7
| » Introduction|| |
Gallbladder cancer (GBC) incidence has a wide variation worldwide as well as within India. GBC is the most frequent malignancy of biliary tract worldwide. Ninety to ninety-five percent of GBCs are adenocarcinomas, whereas squamous cell carcinomas have a small proportion. GBCs are usually detected at an advanced stage due to vague signs and symptoms and have a poor prognosis. Furthermore, the etiology of GBC is still unknown, and the treatment of GBC is ineffective. The highest incidence of GBC is found in Eastern Asia (age-adjusted rates [AARs] 3.3/100,000), South America (AAR 2.9/100,000), and Latin America (AAR 2.4/100,000), whereas global GBC incidence is approximately 2.1/100,000. Eastern Asia alone contributes 45% of the world GBC cases. However, in some parts of Poland, India, Korea, Chile, China, Bangladesh, and Nepal, AAR is more than 10. Females are more prone to GBC compared to males, and studies have shown that the risk varies 2–4 times. In India, GBC varies widely, and population-based cancer registries (PBCRs) data revealed that North India, especially Ganga belts and Eastern regions of the country, had high incidence rates compared to other parts of the country. Urban Kamrup (Assam) had the highest AAR with 17.1/100,000 in females and 8.8/100,000 in males, while the lowest GBC incidence was found in South India. In urban Delhi, GBC among females is the third leading cancer type with AAR 11.8/100,000, and among males its position is ninth with an AAR of 5.2/100,000. A close association of gallstone and GBC has been found, whereas other risk factors for GBC described in various studies are old age, female-sex, obesity, dietary pattern, environmental factors, genetic, female reproductive factors, and chronic inflammation.,,
The present study briefly explains the descriptive statistics of GBC incidence for the year 2012 along with the trend for 25 years (1988–2012). To study the GBC incidence variation in urban Delhi, a time trend analysis using joinpoint regression model was performed. In addition, estimated cumulative risk (0–74) and life-term risk of GBC were also calculated for 25 years.
| » Materials and Methods|| |
The data on GBC incidence during 1988 and 2012 were obtained from Delhi PBCR, one of the oldest cancer registries in India. This registry fulfilled the International Agency for Research on Cancer quality standard and data included in their volumes of five continent series., The International Classification of Disease 9th revision with code 156 used for the period 1988–2000 and 10th revision with code C23 and C24 were utilized for the period 2001–2012. According to the 2011 census, the total population of Delhi was 16,787,941 (urban: 16,368,899; rural: 419,042) with 97.5% of people living in urban areas covering approximately 75% of the total area (1483 sq km). The registry covers only the urban population of Delhi which is 16,333,916 with 8,749,440 males and 7,584,506 females as of 2012. The population at risk during the respective year was estimated from the 1981, 1991, 2001, and 2011 census reports of India using difference distribution method.
AAR per 100,000 was determined by direct method using the world standard population as reference. The estimated cumulative risk (0–74) is the probability that an individual will be diagnosed with cancer before the age of 75 years in the absence of any competing cause of death, assuming that the same trends continue over the period. The life-term risk of one out of n persons who developed GBC before the age of 75 years in the absence of any competing cause of death was determined by 100/cumulative risk.
The incidence of GBC in younger age groups (under 20 years) is rare; thus, trend analysis was done only for the age group 20–75+ according to gender. Furthermore, age and sex-specific trend was also evaluated. Joinpoint regression model developed by the US National Cancer Institute was applied to study the time trend and location of joinpoints (Version 220.127.116.11-January 4, 2017). The estimated annual percentage change (EAPC) of each joinpoint was determined using log linear model, and t-test was applied to test whether EAPC is significantly different than zero. Entire range estimated average annual percentage change (EAAPC) was also determined. The trend coefficient was considered significant if P value of EAPC and EAAPC was <0.05%.
| » Results|| |
Descriptive statistics of 2012
The total GBC cases during 2012 in Delhi were 1116 (361 males and 755 in females) with crude rate 4.0/100,000 and 9.6/100,000 in males and females, respectively. Delhi contributed approximately 6% to the total incidence GBC cases from India.
Descriptive statistics for 1988–2012
A total of 12,410 GBC cases (8400 females and 4010 males) were registered in Delhi during the 25-year period, accounting for 3.0% of male cancer and 6.5% of female cancer cases during this period. The rate of GBC incidence among females is more than double than that among males. The 25-year crude rate and AAR among males were 2.4 and 4.0/100,000, respectively, whereas in females, the rates were 5.8 and 9.0/100000, respectively. In males, 27.58% of total GBC cases registered in Delhi PCBR were <50 years, 54.2% were between 50 and 70 years, and 18.20% cases were more than 70 years old; among females, these percentages were 32.98%, 52.52%, and 14.49%, respectively. The median age of diagnosing GBC in Delhi was 60.13 years in males and 57.22 years in females.
[Figure 1] shows age-specific GBC incidence among males and females. Because most cancers are age dependent, likelihood increases with increasing age. Rates were quite low for both genders in population aged <30 years; after that, it began increasing and caught momentum after 35 years in females, peaking at 70–74 years with a rate of 43.69/100,000, whereas in males, it started increasing after 40 years and the highest rate of 24.04 was observed at 70–74 years.
|Figure 1: Age-specific gallbladder cancer rate by gender in Delhi Urban, 1988–2012|
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The AAR (0–75+) for GBC among males increased by three times with AAR 5.3 in 2012–1.8/100,000 in 1988; among females, this increase was 2.5 times from AAR 11.8 in 2012–4.5 in 1988 [Table 1]. The age and sex-specific truncated AARs of GBC in Delhi during the 25-year period are presented in [Table 2]. The average cumulative risk and lifetime risk of one out of n persons for 25 years was 0.62 (95% confidence interval [CI]: 0.55–0.69), 161 in males, and 1.25 (95% CI: 1.15–1.35), 80 in females.
|Table 1: Age-adjusted rate (0–75+), truncated age-adjusted rate (20–74), cumulative risk (0–74) and life time risk of developing the gallbladder cancer in males and females|
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|Table 2: Gallbladder cancer age-adjusted rates incidence trend according to age among males and females in Delhi from 1988 to 2012|
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Results of joinpoint analysis
The truncated AAR rates from 1988 to 2012 are presented in [Figure 2]. The pattern in both genders was distinctive and had two joinpoints. In males, AAR of GBC increased during 1988–1991 and plateaued till 2005, after which it started increasing with an EAPC of 6.0% (95% CI: 3.6–8.5). The EAAPC was 4.7% (95% CI: 2.2–7.5) which showed significant increase during the 25 years [Table 2]. The truncated AAR was 3.13 in 100,000 in 1988 which increased to 8.28/100,000 in 2012. Similarly, cumulative risk was 0.27 in 1988 which increased to 0.66 in 2012.
|Figure 2: Temporal trend in gallbladder incidence rate in Delhi Urban, 1988–2012|
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In females, the incidence increased at a rate of 20.0% annually till 1992 and then significantly reduced to 2.9% annually in 2004; after 2004, it started increasing with an EAPC of 5.7% (95% CI: 2.9–8.5) [Table 2]. Significant EAAPC 3.5% (95% CI: 0.6–6.5) was observed over the 25-year period. The cumulative risk was 0.56 in 1988 which increased to 1.42 in 2012.
A significant upward trend was observed in both genders in 20–39 age group; 40–49 age group represented an increasing trend of GBC after 2008 in males, whereas in females, a linearly increasing trend was observed during 25 years [Figure 3]. A distinctive trend was observed in males and females before 2005, but thereafter, both showed a significant increasing trend.
|Figure 3: (a) Time trend of gallbladder cancer in Delhi Urban among males in different age-groups, 1988–2012, (b) Time trend of gallbladder cancer incidence in Delhi Urban among females in different age-groups, 1988–2012. Note: The Y-axis scale of males is smaller than Y-axis scale for females for visibility variation|
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A linear positive trend was observed in 50–59 age group in males, whereas in females, AAR increased in the initial years and then decreased in the middle years, and later, started inching up significantly.
The 60+ age group depicted similar trend in both genders; first increased, decreased in the middle years, and increased after 2005 [Figure 3]. The estimated EAPC and EAAPC of respective years are presented in [Table 2].
| » Discussion|| |
The time trend analysis revealed a significant increase in GBC over 25 year period in urban Delhi among both genders; other population registries in India have also showed similar increasing trends. The AAR of GBC in Delhi was comparatively higher than other metropolitan cities in India. Females predominance over males has been reported within the country as well as worldwide. In Delhi, GBC cases among females even surpassed ovarian cancer., The majority of GBC cases were diagnosed in the 5th to 7th decades, which was similar to a study reported from China. The incidence rank of GBC increased in both genders; males rank moved from 24th in 1998 to 9th in 2012, while in females, it increased from 5th to 3rd rank.
The cumulative risk (0–74) and lifetime risk in Delhi during 2012 were 0.66 and 152 in males and 1.42 and 71 in females, respectively. These values are quite higher than Indian values, which were 0.17 and 588 in males and 0.24 and 417 in females, respectively. The cumulative risk increased more than twice in both genders [Table 1]. The incidence of GBC was relatively less among the younger population (<35 years) than the older age groups and conformed with incidences reported in other studies., GBC occurred at an early age in females than males in Delhi, and the median age for both genders was higher in urban Delhi urban compared to a Northeastern study. However, United States had a higher median age of GBC than Delhi, which could be partly explained by higher LEB (life expectancy at birth).
GBC is closely associated with cholelithiasis (gallstone) and chronic inflammation and almost 80% of GBC cases have cholelithiasis; however, only a fraction (0.5%–3%) of patients having cholelithiasis develop GBC in the future. The risk factors of GBC are similar to gallstones and fall into modifiable and nonmodifiable categories. The nonmodifiable risk factors are beyond human control such as old age, female sex, family history, and menopause; whereas modifiable factors can be controlled such as obesity, smoking, alcohol, dietary intake pattern, and exercise. The effect of smoking and alcohol on GBC is still unclear. A meta-analysis of observational studies found that smokers had an increased risk of developing GBC compared to nonsmokers (summary relative risk 1.45 [95% CI: 1.11–1.89]). A case–control study conducted in Delhi showed that both smoking and alcohol were positively associated with GBC., Use of tobacco products is increasing in Delhi among both sexes. A recent survey showed that smoking increased by 220% in males from 1998 to 2010, whereas in females during 2005–2010 increase in smoking was more than double. Other factors described in the literature responsible for GBC include bacterial infection; history of typhoid, gallbladder polyps, primary sclerosing cholangitis, genetics; stone size; and duration of gallstone.,,
Lifestyle and dietary habits play a vital role in the development of GBC in males and females. In addition to these risk factors, in females, reproductive factors are also associated with GBC, early menarche <13 years and higher parity >3 have been shown to increase the risk of GBC., Intake of fast food and fried food and a sedentary lifestyle is growing rapidly among urban Delhi population, especially among the young during the last two decades, which is the main cause for increase in obesity. A cross-sectional study revealed that Delhi had the highest prevalence of overweight (30.4%) and (12.12%) obese individuals, and the number of overweight/obese individuals was maximum in the age group of 41–50 years. The prevalence of obesity is increasing among Delhi adolescents; a study showed that prevalence of obesity (>95th percentile of reference population) significantly increased from 9.8% in 2006 to 11.7 in 2009. Physical inactivity is directly related to obesity; a recent Indian survey on physical inactivity reported that 58.7% males were inactive (MET <600 met minutes) while 71.2% of females were inactive. Obese individuals have a higher risk of developing GBC; the relative risk for obesity was 1.88 (95% CI: 1.66–2.13) in females and 1.35 (95% CI: 1.09–1.68) in males. Exercise and Yoga may be useful in controlling obesity and may help in preventing GBC. Obesity and lack of physical activity are probable reasons for increasing GBC incidence in Delhi.
Bile is the main source for removing toxic metabolites. Environmental carcinogens might play a role in developing GBC as excretion of environmental carcinogens in bile increases the likelihood of GBC. Heavy metals such as cadmium, chromium, and lead in drinking water are known chemical carcinogens. Shukla et al. found significantly higher level of these metals in GBC patients compared to noncarcinogens gallstone patients. The main source of drinking water for Delhi is Ganga and Yamuna river water; both these rivers are now contaminated with industrial waste and contain several heavy metals. Indian government is taking steps to improve the water quality of these rivers, but these plans are on still on-paper and awaiting implementation. Immediate steps are required to stop the flow of untreated water into these rivers because this not only will decrease the quality of drinking water but also infect vegetable and crop production in these belts. The cumulative effect of these two may be more dangerous for human health in the future.
Another major cause of GBC increase may be migration from various states, especially individuals who previously resided in the Ganga belt and eastern region. Those residing near the Ganga belt have odds of suffering from GBC of 2.3 times compared to controls. The net migration in Delhi steadily increased from 6.34 lakhs during 1961–1971 to 22.2 lakhs during 2001–2011. The major influx of population to Delhi is from Uttar Pradesh followed by Bihar, Haryana, and Uttaranchal. These four states contributed to more than 60% of migration. Population growth and enhancement of life expectancy at birth (LEB) in urban Delhi over 25 years increased the absolute number of GBC cases. The life expectancy in urban Delhi population is 73.5 years, with females having higher LEB than males.
| » Conclusion|| |
The prevalence of modifiable risk factors of GBC increased in urban Delhi over time and probably is the reason for increased GBC incidence in urban Delhi. Stringent and quick steps are required to stop the flow of industrial waste directly into rivers to reduce the presence of heavy metals in drinking water. This will not only reduce the incidence of GBC but will also be effective in controlling other cancers. It is important to increase awareness among adolescents and young population about the side effects of excessive consumption of fast/junk food, sedentary lifestyle, as well as the benefits of Yoga and physical fitness programs in a large scale.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Hundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. Clin Epidemiol 2014;6:99-109.
Goetze TO, Paolucci V. Adequate extent in radical re-resection of incidental gallbladder carcinoma: Analysis of the German registry. Surg Endosc 2010;24:2156-64.
Shukla VK, Khandelwal C, Roy SK, Vaidya MP. Primary carcinoma of the gall bladder: A review of a 16-year period at the university hospital. J Surg Oncol 1985;28:32-5.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al
. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://www.globocan.iarc.fr
. [Last accessed on 2017 Apr 05].
Miller G, Jarnagin WR. Gallbladder carcinoma. Eur J Surg Oncol 2008;34:306-12.
Sachidananda S, Krishnan A, Janani K, Alexander PC, Velayutham V, Rajagopal S, et al.
Characteristics of gallbladder cancer in South India. Indian J Surg Oncol 2012;3:228-30.
National Cancer Registry Programme. Three Year Report of Population Based Cancer Registries: 2012-2014 Report of 27 PBCRs in India. Bangalore, India; 2016. p. 9-16.
Pandey M. Risk factors for gallbladder cancer: A reappraisal. Eur J Cancer Prev 2003;12:15-24.
Pandey M, Shukla VK. Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. Eur J Cancer Prev 2003;12:269-72.
Tamrakar D, Paudel I, Adhikary S, Rauniyar B, Pokharel P. Risk factors for gallbladder cancer in Nepal a case control study. Asian Pac J Cancer Prev 2016;17:3447-53.
Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, et al
. Cancer Incidence in Five Continents. IARC Scientific Publication no. 160. Vol. 9. Lyon, France: IARC; 2007. p. 229.
Forman D, Bray F, Brewster DH, Mbalawa CG, Kohler B, Pineros M, et al
. Cancer Incidence in Five Continents. IARC Scientific Publication no. 164. Vol. 10. Lyon, France: IARC; 2007. p. 550.
Census of India, Registrar General of India, Socio Cultural Tables, C14 Series – Socio Cultural Tables; Population by 5 Years Age Group, by Residence and Sex. New Delhi; 1981, 1991, 2001, 2011. Available from: http://www.censusindia.gov.in
. [Last accessed on 2017 Mar 22].
Takiar R, Shobana B. Cancer incidence rates and the problem of denominators - a new approach in Indian cancer registries. Asian Pac J Cancer Prev 2009;10:123-6.
Boyle P, Parkin DM. Statistical method for registries. In: Jensen OM, Parkin DM, Maclennan R, Muir CS, Skeet RG, editors. IARC Scientific Publication No 95. Lyon: International Agency for Research on Cancer; 1991. p. 131-50.
Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med 2000;19:335-51.
Murthy NS, Rajaram D, Gautham MS, Shivraj NS, Pruthvish S, George PS, et al
. Trend in incidence of gallbladder cancer – Indian scenario. Gastrointestinal Cancer Targets Theory 2011;1:19.
Henley SJ, Weir HK, Jim MA, Watson M, Richardson LC. Gallbladder cancer incidence and mortality, United States 1999-2011. Cancer Epidemiol Biomarkers Prev 2015;24:1319-26.
Bhagabaty SM, Sharma JD, Krishnatreya M, Nady P, Kataki AC. Profiles of gallbladder cancer reported in the hospital cancer registry of a regional cancer center in the North-East India. Int J Res Med Sci 2014;2:1683-6.
Wenbin D, Zhuo C, Zhibing M, Chen Z, Ruifan Y, Jie J, et al.
The effect of smoking on the risk of gallbladder cancer: A meta-analysis of observational studies. Eur J Gastroenterol Hepatol 2013;25:373-9.
Tyagi BB, Manoharan N, Raina V. Risk factors for gall bladder cancer: A population based case-control study in Delhi. Indian J Med Paediatr Oncol 2008;29:16-26. [Full text]
Jain K, Sreenivas V, Velpandian T, Kapil U, Garg PK. Risk factors for gallbladder cancer: A case-control study. Int J Cancer 2013;132:1660-6.
Mishra S, Joseph RA, Gupta PC, Pezzack B, Ram F, Sinha DN, et al.
Trends in bidi and cigarette smoking in India from 1998 to 2015, by age, gender and education. BMJ Glob Health 2016;1:e000005.
Goel S, Tripathy JP, Singh RJ, Lal P. Smoking trends among women in India: Analysis of nationally representative surveys (1993-2009). South Asian J Cancer 2014;3:200-2. [Full text]
Lowenfels AB. Does bile promote extra-colonic cancer? Lancet 1978;2:239-41.
Sheth S, Bedford A, Chopra S. Primary gallbladder cancer: Recognition of risk factors and the role of prophylactic cholecystectomy. Am J Gastroenterol 2000;95:1402-10.
Shukla VK, Chauhan VS, Mishra RN, Basu S. Lifestyle, reproductive factors and risk of gallbladder cancer. Singapore Med J 2008;49:912-5.
Aggarwal N, Kaur H, Saklani R, Saba N, Choudhary S, Dogra S, et al
. Prevalence of obesity and associated hypertension and diabetes in Delhi, metropolitan city of India. Indian J Med Specialities 2015;6:82-7.
Gupta DK, Shah P, Misra A, Bharadwaj S, Gulati S, Gupta N, et al.
Secular trends in prevalence of overweight and obesity from 2006 to 2009 in urban Asian Indian adolescents aged 14-17 years. PLoS One 2011;6:e17221.
Anjana RM, Pradeepa R, Das AK, Deepa M, Bhansali A, Joshi SR, et al.
Physical activity and inactivity patterns in India – Results from the ICMR-INDIAB study (Phase-1) [ICMR-INDIAB-5]. Int J Behav Nutr Phys Act 2014;11:26.
Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: A meta-analysis. Br J Cancer 2007;96:1457-61.
Shukla VK, Prakash A, Tripathi BD, Reddy DC, Singh S. Biliary heavy metal concentrations in carcinoma of the gall bladder: Case-control study. BMJ 1998;317:1288-9.
Census of India, Registrar General of India. Migration Tables, New Delhi; 2011 Available from: http://www.censusindia.gov.in
. [Last accessed on 2017 Mar 22].
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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