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Nasopharyngeal and hypopharyngeal carcinoma risk among immigrants in Sweden
Article first published online: 2 MAR 2010
Copyright © 2010 UICC
International Journal of Cancer
Volume 127, Issue 12, pages 2888–2892, 15 December 2010
How to Cite
Mousavi, S. M., Sundquist, J. and Hemminki, K. (2010), Nasopharyngeal and hypopharyngeal carcinoma risk among immigrants in Sweden. Int. J. Cancer, 127: 2888–2892. doi: 10.1002/ijc.25287
- Issue published online: 2 MAR 2010
- Article first published online: 2 MAR 2010
- Manuscript Accepted: 18 FEB 2010
- Manuscript Received: 3 DEC 2009
- DKFZ Guest Scientist Program
- Deutsche Krebshilfe
- Swedish Cancer Society
- Swedish Council for Working Life and Social Research
- hypopharynx carcionam;
- nasophayrnx carcinoma;
Environmental exposures, particularly infection with Epstein-Barr virus (EBV) and tobacco, are known risk factors for oral cancer. Studies in migrants may provide valuable insight into the environmental and genetic etiology of cancer. We wanted to define nasopharyngeal and hypopharyngeal carcinoma among immigrants in Sweden. The nationwide Swedish Family-Cancer Database (FCD) was used to calculate standardized incidence ratios (SIRs) for nasopharyngeal and hypopharyngeal carcinomas among the first-generation immigrants compared to the native Swedes. The FCD included 1969 and 691 cases of nasopharyngeal and hypopharyngeal carcinoma in the male and female Swedes and 178 and 65 cases in immigrants, respectively. The median age at diagnosis (years) was 63 among Swedes and 55 among immigrants. The risk of nasopharyngeal carcinoma was significantly higher in male (SIR = 35.6) and female (24.6) Southeast Asians, male (12.4) and female (34.7) North Africans, male (4.9) and female (10.9) Asian Arabs and some other male Asians immigrants (6.2 to 6.7). Among immigrants from European countries, only the men from former Yugoslavian showed an elevated risk (2.7). Hypopharyngeal carcinoma risk was only increased among the male immigrants from the Indian Subcontinent (5.4). Early life infection with EBV in countries of origin and probably a minor contribution by tobacco smoking may be the main environmental exposures influencing nasopharyngeal carcinoma risks among immigrants to Sweden. The high rates of hypopharyngeal carcinoma among Indian immigrants may point to a continued using of smokeless tobacco.
Nasopharyngeal carcinoma incidence varies wide geographically. It is generally a rare malignancy (1/100,000 per year) in the developed countries but relatively high rates are reported across Asia (10/100,000 among men).1 Southeast Asia, Southern China, Malaysian region of Sarawak and Northern Africa appear to have an exceptionally high incidence (20/100,000 among men).2, 3
Epstein-Barr Virus (EBV) is associated with nasopharyngeal carcinoma.4 The extremely heterogeneous geographical and ethnic distribution of nasopharyngeal carcinoma incidence is linked to EBV infection, relative risk based on serological tests being around 50.5, 6 Nasopharyngeal cancer shows familial clustering, and genetic susceptibility interacting with EBV infection and other environmental factors may play an important role. The consumption of salty foods has also been consistently linked with nasopharyngeal carcinoma risk (2–3-fold).7 That tobacco smoking increases the risk of nasopharyngeal carcinoma (2–6-fold), but the role of alcohol is less clear.4 Exposure to chemicals and solvents has been associated with excess risk of nasopharyngeal carcinoma.8
Hypopharyngeal carcinoma is less common than nasopharyngeal carcinoma in the World. Some regions in France (10/100,000), India, Slovak Republic and Croatia (5/100,000) were reported as highest incidence rate for male hypopharyngeal carcinoma.9, 10 The reason for this high risk in these particular populations is unclear.11 However, chewing tobacco products are reported as the main risk factor for hypopharyngeal carcinoma, with a high prevalence rate in India.12
Studies on migrants may provide valuable insight into the etiology of cancer and clarify genetic and environmental interactions.13 Sweden is an excellent country to study cancer in immigrants because of its uniform cancer registration, health care system and large number of immigrants. In the nationwide Swedish Family-Cancer Database (FCD) with 11.8 million individuals, about 1.8 million are immigrants.14 In this report, we studied risk of nasopharyngeal and hypopharyngeal carcinomas in the first-generation immigrants to Sweden to search for etiological clues. This study also provided supplementary and confirmatory data on the incidence of these carcinomas in various countries.
Material and Methods
The updated version of FCD (2008, VIII) was used for this study.14 This Database contained those born in Sweden since 1932 with their biological parents and additionally, the data on immigrants were included. The parental information was classified according to the country of birth. The first-generation immigrants were defined as those born outside of Sweden without identified parents in the Database. The countries, included in each birth region, were classified according to their population size or geographical setting.14 Whenever feasible, large immigrant populations, for example Iraqis and Iranians, were kept as separate groups.
Start of follow-up was defined as the birth year, the date of immigration or January 1st, 1958, whichever came latest. If the date of immigration was missing, the start of follow-up was defined as the first year of presence at census. End of follow-up was defined as the earliest date: the date of diagnosis of cancer, death or emigration, end of the last year of presence at census, or the closing date of our study, December 31st, 2006.
The standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected number of cases. The expected numbers were calculated by applying 5-year age groups, sex and time period (10-year bands from 1958 to 2006) specific incidence rate of the native Swedish population, as the reference population, to a set of age-sex-period specific person-year at risk among immigrants. Confidence intervals (95% CI) were calculated assuming a Poisson distribution. SAS software ver.9.1 was used for the data analysis.
The FCD included 1969 male and 691 female cases of nasopharyngeal and hypopharyngeal carcinoma in the native Swedish population and 178 and 65 cases in immigrants, respectively (Table 1). The median age at immigration was 32 years and the median age at cancer diagnosis was 55 years in immigrants (Table 1).
As compared to the native Swedish population, the risk of nasopharyngeal carcinoma was significantly higher in male (SIR = 35.6) and female (24.6) Southeast Asians, male (12.4) and female (34.7) North Africans, male (4.9) and female (10.9) Asian Arabs and other male Asians (6.2 to 6.7) (Table 2). Among immigrants from the European countries, only the men from former Yugoslavian showed an increased risk (2.7).
We observed 84 and 26 cases of hypopharyngeal carcinoma among male and female immigrants, respectively. Only male immigrants from the Indian Subcontinent had an increased risk (5.4) of hypopharyngeal carcinoma as compared to native Swedes (Table 2).
This study showed significantly higher risks of nasopharyngeal carcinoma among male and female Southeast Asians, Asian Arabs and North Africans immigrants and among men from former Yugoslavia compared to the native Swedish population.
A specific feature of EBV-associated malignancies is variation in incidence and the proportion of EBV-positive cancer in different geographic regions. The incidence of nasopharyngeal carcinoma is higher in Southern China, Southeast Asia, North Africa and some part of Middle East than in other regions of the world.15 Tobacco, cannabis, domestic cooking fumes and EBV activators such as butyric acid were reported as the risk factors for nasopharyngeal carcinoma in western North Africa.16–18 Our findings are compatible with the geographical pattern of EBV infection and the report of “Cancer Incidence in Five Continents.”1 For example, this source gave incidence rates of nasopharyngeal carcinoma for Southeast Asian men and women as 11.0–26.9/100,000 and 3.6–10.1/100,000 compared to 0.4/100,000 and 0.2/100,000 among Swedes, respectively.
The average period between age at immigration and age at diagnosis was 2 decades in our data (Table 1). Considering the high risks (SIRs 20–30) among Southeast Asians and North Africans, despite moving to countries where the incidence is low, it is likely that the cause is exposure to EBV in early life; whether the genetic background play a role remains to be established. Smoking or dietary habits may contribute to the excess, but their conferred risks are too low to explain the observed risks. As these immigrants arrived in Sweden in their 20s and 30s, EBV appeared to have inflicted a permanent damage by that age. It is interesting that the risks are not much below those reported from endemic areas (∼50) which may be explained by the low background rate in Sweden. Men were more commonly affected in Sweden as in the endemic areas. The high risks in female immigrants may similarly be explained by their lower background rates. Contribution by dietary intake of salty food, especially in childhood,19 smoking and occupational exposures in the host country cannot be excluded, but the magnitude of these effects is small compared to EBV.20
However, the increased risk for nasopharyngeal cancer among female North African migrants was based on two cases only; such results could be due to random variation.
Among the large group of immigrants in Sweden, only immigrants from the Indian Subcontinent had higher risks for hypopharyngeal carcinoma. The use of chewing tobacco is endemic in India.21 Studies showed that the South Asians immigrants in USA and UK have high rate of smokeless tobacco consumption.22, 23 The high risk among Indian Subcontinent immigrants may be due to that these immigrants, such as the immigrants in USA or UK, have been remained to their habit on chewing tobacco. However, such data were unavailable in the Database.
In conclusion, early life time exposure to EBV may be the main environmental exposures influencing nasopharyngeal carcinoma risks among immigrants in Sweden. Because the risk for lung cancer, a proxy for smoking prevalence,24 among the immigrants from high risk of nasopharyngeal carcinoma areas has equaled that of the Swedes,25 smoking may not be an important contributor to the findings. The high rates of hypopharyngeal carcinoma among Indian immigrants may point to a continued consumption of smokeless tobacco or long-lasting damage from earlier consumption.
- 1Cancer incidence in five continents, Vol. IX. Lyon, IARC: IARC Scientific Publications, No. 160, 2007., , , , , , .
- 4IARC monographs on the evaluation of carcinogenic risks to humans, Vol 70, Epstein-Barr virus and Kaposi's sarcoma herpesvirus/human herpesvirus 8. ed. IARC, 1997.
- 9GLOBOCAN 2002.Cancer incidence, mortality and prevalence worldwide. IARC CancerBased. Lyon, France: IARC Press, 2002., , .
- 14The Swedish family-cancer database 2009: prospects for histology-specific and immigrant studies. Int J Cancer 2009 In press, (Epub ahead of print)., , , , .
- 18Nasopharyngeal carcinoma: An epidemiological approach to carcinogenesis. Cancer Surveys 1999; 33: 125–55., , .