There is a striking increase in the incidence of Non-Hodgkin's Lymphoma (NHL) worldwide since the early 1970s. NHL is generally higher in US, Europe and Australia and lower in Asia and the Far East. Local data from the Singapore Cancer Registry Report No.6 shows our incidence rate to be between the West and the other parts of Asia and that it is also on a rising trend.
This is evident when comparing the age-standardized rates for males and female in 1998 – 2002 which are 8.2 and 5.0 per 100,000 respectively compared with 7.5 and 4.4 per 100,000 in 1993-1997 and 3.1 and 1.9 per 100,000 in 1968-1972 1. This may be partly due to HIV/AIDS, changes in pathological classification and improved diagnostic capabilities.
However, these can not account for the magnitude of change and it is recognized that there is a true rise in the incidence and mortality from lymphoma over the past several decades, making this group of diseases an increasingly important burden for the country. There are gender differences seen with the rate of increase greater in females than males.
Between ethnic groups, Malay females were at higher overall risk compared with their Chinese counterparts 1. For the period 1998 to 2002, Non-Hodgkin's Lymphoma ranks as the 8 th most common male cancer and 10 th most common female cancer. However for the age group 15 to 34 years old it ranks 1 st and 4 th most common male and female cancer, respectively 2.
Risk Factors for NHL
Studies found that changes in NHL rates over time could not be fully explained by diagnostic improvements, changes in NHL classification and /or the increase in AIDS-related NHL. Epidemiological studies suggested that increased exposure to risk factors may be important.
The risk factors which have been studied include occupational and environmental factors, lifestyle and personal factors, family history and genetic factors, immune function and personal medical history 3.
Review and evaluation of epidemiological studies of occupational and environmental pesticide exposure have not identified a specific agent or chemical consistently associated with NHL.
The results have been mixed and have not provided consistent significant positive associations. However there seems to be an inverse association between UV radiation exposure and NHL risk. Several small studies have also reported positive associations between occupation as a school teacher and risk of NHL but the cause has not yet been determined.
Studies evaluating lifestyles and personal factors are usually inconsistent with the exception of alcohol consumption which appears to be inversely associated with NHL. Smoking also does not appear to associated with NHL but there may be associations with follicular lymphoma.
Fish intake has been associated with non-significant decreased risk of NHL but not intake of omega-3 fatty acids.
Data is limited and results are not consistent for estimation of associations with types of red meat or cooking methods. Saturated fat intake is associated with increase risk whereas vegetable intake was inversely associated. Neither obesity nor physical activity been consistently associated with NHL. The only significantly increased association is between hair dye use and NHL risk.
Family history and genetic factors increase risk of NHL in people whose relatives previously were diagnosed with NHL, but hereditary factors account only for a small percentage of NHL and are unlikely to explain the increase in NHL incidence.
Several genetic polymorphisms associated with the risk of NHL suggest that single nucleotide polymorphisms (SNPs) in tumor necrosis factor (TNF) and interleukin-10 (IL10) are associated with risk of NHL, especially diffuse large B –cell lymphoma. There are few studies that have examined the potential interaction between germline and environmental or lifestyle factors and results are inconsistent.
Autoimmune disorders that are strongly associated with NHL are systemic lupus erythematosus (SLE), Sjogren’s syndrome, rheumatoid arthritis and celiac disease. There is no evidence to support an excess risk of NHL in other autoimmune disorders including diabetes type I, inflammatory bowel disorders, psoriasis and sarcoidosis. Patients with congenital immunodeficiency syndromes such as Wiskott-Aldrich syndrome, ataxia telangiectasia and severe combined immunodeficiency will develop NHL during their lifetime.
Increased risks of NHL have been reported for HIV, Epstein-Barr virus, human herpesvirus 8 and human T-cell lymphtropic virus (HTLV-1) and Helicobactoer pylori. However infectious agents account for only a small proportion of newly diagnosed NHL.
Singapore Lymphoma Study
Since 2004, Professor Adeline Seow, Community, Occupational and Family Medicine, National University Singapore, has been conducting a multi-centre epidemiological case-control study in Singapore for local patients with NHL to investigate the reason for the rising incidence of this disease in Singapore.
National Cancer Centre is a participating centre. The purpose of this study is to evaluate some of the environmental risk factors that have been studied in association with NHL and their relevance to the local population including exposure to pesticides and chemicals.
There would also be study of genetic polymorphisms and whether there are genetic predispositions that interact with the environmental and lifestyle factors in the local patients.
Conclusion
There is strong evidence of rising incidence of NHL in Singapore over the past 25 years with the greatest increase seen in females. Due to the geographic and demographic factors, there is a potential for a comprehensive study to evaluate the etiological factors contributing to this rise in this multi-ethnic society.
Dr Miriam Tao
Senior Consultant
Department of Medical Oncology
References:
- Cancer. 1996 May 1;77(9):1899-904. Non-Hodgkin's lymphoma in an Asian population: 1968-1992 time trends and ethnic differences in Singapore. Seow A, Lee J, Sng I, Fong CM, Lee HP.
- Seow A. et al. Trends in Cancer incidence in Singapore, 1968-2002. Singapore : Singapore Cancer Registry, 2004.
- 1: Int J Cancer. 2007;120 Suppl 12:1-39. The non-Hodgkin lymphomas: a review of the epidemiologic literature. Alexander DD, Mink PJ, Adami HO, Chang ET, Cole P, Mandel JS, Trichopoulos D.
