Abstract

Background: Gallbladder cancer (GBC), a common cancer surrounding the Gangetic belt of India, accounts for 80%–90% of biliary tract cancers. GBC incidence shows striking geographical variation in India. Materials and Methods: We used the data from the National Cancer Registry Programme for the year 2001–2014 to study the time trends of GBC in the high- and low-risk geographical regions of India. Annual percentage change (APC) in age-adjusted incidence rates was computed by log-linear regression model. Results: Among females, a statistically significant increase in trend was observed in Cachar (APC: 7.0, P = 0.02), Delhi (APC: 4.0, P = 0.04), and Kamrup (APC: 4.3, P = 0.02) marked under high-risk region and in Bengaluru (APC: 5.7, P = 0.04) and Pune (APC: 3.4, P = 0.04) marked under low-risk region. Among males, increasing but statistically nonsignificant trends were observed in Cachar, Dibrugarh, Kamrup, Nagpur, and Sikkim, whereas decreasing trends were observed in Bengaluru, Barshi, Bhopal, and Kolkata. Aurangabad showed a statistically significant decrease in trend (APC: −14.5, P < 0 class="b" xss=removed>Conclusion: The time trend and pattern of GBC have striking differences within the country as well as in state. Further large-scale region-wise studies are needed to find the risk factors of GBC.

Introduction

Gallbladder cancer (GBC) is less common in developed countries while its incidence is highest in some parts of India, Chile, and Mexico.[1] Within India, the states such as Assam (rate ratio [RR] [95% confidence interval [CI] – female: 7.18 [4.89–10.55] and male: 3.61 [2.44–5.36]) and Delhi (RR – female: 4.70 [3.93–5.61] and male: 2.04 [1.61–2.60]) showed highest rate compared to South India (RR – female: 0.39 [0.24–0.66] and male: 0.53 [0.33–0.85]).[2] To investigate secular trends in GBC over the past 14 years, we conducted this study to estimate the annual percentage change (APC) in the incidence rate within different regions of India and performed a comprehensive analysis to understand the time trends in different geographical regions of India.

Materials and Methods

Incidence data

We retrieved age-adjusted incidence rate (AAR) per 100,000 of GBC from the National Cancer Registry Programme (NCRP) database,[3] for the period of 14 years (2001–2004 to 2012–2014). The NCRP database includes 30 population-based cancer registries (PBCRs), namely, Ahmedabad, Aurangabad, Bengaluru, Barshi, Bhopal, Cachar, Chennai, Delhi, Dibrugarh, Kamrup, Kolkata, Kollam, Manipur, Meghalaya, Mizoram, Mumbai, Nagaland, Nagpur, Naharlagun, Pasighat, Patiala, Pune, Sikkim, Thiruvananthapuram, Tripura, Wardha, Sangrur, Mansa, Chandigarh, and SAS Nagar. However, for trend analysis, we considered only 18 registries having AAR available for at least three time periods.

Definition of high- and low-risk regions

We divided Indian states and territories into high- and low-risk regions using incidence rates extracted from the PBCRs. States were considered to be in the high-risk region if PBCR existing in the state observed average AARs of >5.0 per 100,000 persons.[2] Others were considered as low-risk regions. According to the definition, Cachar, Delhi, Kamrup, Dibrugarh, Kolkata, and Sikkim were in the high-risk region, and the rest of the registries were considered to be in the low-risk region. For comparison, average AARs of all registries from high- and low-risk regions were taken for four time periods (2001–2004 to 2012–2014).

Estimation of annual percentage change

APC is a summary measure of the trend over a prespecified fixed interval. APC was estimated independently for both the genders for the selected 18 registries, namely, Aurangabad, Bengaluru, Barshi, Bhopal, Cachar, Chennai, Delhi, Dibrugarh, Kamrup, Kolkata, Kollam, Manipur, Mizoram, Mumbai, Nagpur, Pune, Sikkim, and Thiruvananthapuram for the time period of 2001–2004 to 2012–2014.

Trend was estimated using Joinpoint trend analysis software by the National Cancer Institute.[4],[5] APC was considered statistically significant if P value at 95% CI was ≤0.05.

Results

[Table 1] and [Table 2] show gender-wise AAR for four time periods (2001–2004 to 2012–2014) in the 18 registries. There are substantial differences in the rates for both the genders, with high rates in Delhi, Cachar, Dibrugarh, and Kamrup and with lowest rates in Bengaluru, Barshi, Chennai, and Aurangabad. Among females, statistically significant increasing trends were observed in Bengaluru, Cachar, Delhi, Kamrup, and Pune, whereas the rates were decreasing in Aurangabad, Barshi, and Manipur. Among males, increasing but statistically nonsignificant trends were observed in Cachar, Dibrugarh, Kamrup, Nagpur, and Sikkim, whereas decreasing trends were observed in Bengaluru, Barshi, Bhopal, and Kolkata. Aurangabad showed a statistically significant decrease in trend (APC: −14.5, P < 0>

| Figure 1  Trends in age-adjusted incidence rates of gallbladder cancer in the high- and low-risk regions. Data for Figure 1 are provided as supplementary table|

1. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide by International Agency for Research on Cancer. Available from: http://www.globocan.iarc.fr/. [Last accessed on 2018 Nov 01].
2. Mhatre SS, Nagrani RT, Budukh A, Chiplunkar S, Badwe R, Patil P. et al. Place of birth and risk of gallbladder cancer in India. Indian J Cancer 2016; 53: 304-8
3. National Cancer Registry Programme by Indian Council of Medical Research. Available from: http://www.ncrpindia.org/. [Last accessed on 2018 Nov 01].
4. Joinpoint Trend Analysis Software (Version 4.6.0.0) by National Cancer Institute. Available from: https://www.surveillance.cancer.gov/joinpoint/. [Last accessed on 2018 Nov 01].
5. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med 2000; 19: 335-51
6. Mhatre S, Wang Z, Nagrani R, Badwe R, Chiplunkar S, Mittal B. et al. Common genetic variation and risk of gallbladder cancer in India: A case-control genome-wide association study. Lancet Oncol 2017; 18: 535-44
7. Mhatre S, Chatterjee N, Dikshit R, Rajaraman P. et al. Genetics of gallbladder cancer – Authors' reply. Lancet Oncol 2017; 18: e97
8. Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003; 4: 167-76
9. Randi G, Franceschi S, La VecchiaC. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006; 118: 1591-602
10. Hundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. Clin Epidemiol 2014; 6: 99-109

| Figure 1  Trends in age-adjusted incidence rates of gallbladder cancer in the high- and low-risk regions. Data for Figure 1 are provided as supplementary table|

1. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide by International Agency for Research on Cancer. Available from: http://www.globocan.iarc.fr/. [Last accessed on 2018 Nov 01].
2. Mhatre SS, Nagrani RT, Budukh A, Chiplunkar S, Badwe R, Patil P. et al. Place of birth and risk of gallbladder cancer in India. Indian J Cancer 2016; 53: 304-8
3. National Cancer Registry Programme by Indian Council of Medical Research. Available from: http://www.ncrpindia.org/. [Last accessed on 2018 Nov 01].
4. Joinpoint Trend Analysis Software (Version 4.6.0.0) by National Cancer Institute. Available from: https://www.surveillance.cancer.gov/joinpoint/. [Last accessed on 2018 Nov 01].
5. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med 2000; 19: 335-51
6. Mhatre S, Wang Z, Nagrani R, Badwe R, Chiplunkar S, Mittal B. et al. Common genetic variation and risk of gallbladder cancer in India: A case-control genome-wide association study. Lancet Oncol 2017; 18: 535-44
7. Mhatre S, Chatterjee N, Dikshit R, Rajaraman P. et al. Genetics of gallbladder cancer – Authors' reply. Lancet Oncol 2017; 18: e97
8. Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003; 4: 167-76
9. Randi G, Franceschi S, La VecchiaC. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006; 118: 1591-602
10. Hundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. Clin Epidemiol 2014; 6: 99-109