Hodgkin’s Lymphoma: An Environmental Scan

Table of Contents

3.5 Risk Factors

Overall, the cause of HL is largely unknown and it is important to note that many individuals, who have HL, do not have any associated risk factors. However, research has established a number of risk factors that can increase the likelihood of having the disease and include; demographic characteristics such as age, sex, socio-economic status and ethnicity; medical history including having a relative with HL and other clinical factors such as a compromised immune system and/or particular infections.

One of the most significant negative risk factors associated with HL is being older. Older adults are more likely to have advanced and aggressive disease; they too experience increased toxicity from treatment, have shorter survival periods and an increased number of deaths related to treatment (Klimm, Diehl, and Andreas Engert 2007). Considering global rates across all sub-types, HL is more common among men. Caucasians are more likely than African Americans or Asians to have HL and Jewish ancestry is modestly associated with an increased risk of developing HL, even after correcting for socioeconomic status (Ariad et al. 2009) (Raemaekers and van der Maazen 2008)  (Gutensohn 1982). In particular, HL in young adulthood has been associated with small family size, single family housing, and relatively high maternal education (Pahwa et al. 2009) (Clarke et al. 2005).

Concerning family history and HL, people with a first degree relative with the disease have an increased risk of developing this cancer. In particular, siblings of those with Hodgkin’s lymphoma have a higher risk (Paltiel 2008) (Alexander 1990). First-degree relatives of patients with HL are approximately 3 times more likely to develop the disease than the general population.  Genetic predisposition appears to be most evident in twins. When one fraternal twin has HL, the other faces approximately a 7 times greater chance of getting the disease and when one identical twin develops HL, the other twin’s risk of the disease has been reported to be almost 100 times that of the general population respectively (Mack et al. 1995). In general, the field of genetic research into HL has far to go and there is some evidence to suggest a vulnerability on both chromosomes 2 and 4 may play a role in the development of HL (Paltiel 2008).

Having a compromised immune system or an altered state of the body’s immune system such as when an individual has an auto-immune disease (e.g., rheumatoid arthritis, lupus, multiple sclerosis, under- or overactive thyroid). The result of infections such as AIDS or after certain types of transplants are all associated with a higher risk of HL (Punnett, Tsang, and Hodgson 2010) (Grulich et al. 2007) (Zintzaras, Voulgarelis, and Moutsopoulos 2005). Infectious etiology or causes of HL is becoming more understood among researchers and clinicians including how infections such as mononucleosis (IM), Epstein-Barr (EBV), HIV and other viruses are associated with HL.

Interestingly, a study published in 2009 and completed in Denmark reported an association among tonsillectomy, tonsillitis and HL (Vestergaard et al. 2010).The literature has reported an increased risk of HL for individuals with previous IM infections which are caused by the EBV virus. Recent studies have confirmed the elevated risk, especially among individuals who were infected with IM between the ages of 15 and 34 (Hjalgrim et al. 2000). EBV infects the B-cells and causes an illness known as infectious mononucleosis (sometimes referred to as “mono”). In people with mono, the body’s T-cells seek out and kill the infected B-cells. However, if the patient is experiencing a shortage of T-cells, the EBV-infected B-cells are permitted to build up within the bloodstream and increase the risk for genetic mutations that can cause lymphoma. The increased risk remains high for up to 20 years after infection. For many cases of cHL, the large Hodgkin and Reed-Steenberg (HRS) cells are infected with the Epstein-Barr virus (EBV) and EBV is considered a tumor virus in this particular cancer, thus the Epstein-Barr virus (EBV) is strongly associated with HL (Weiss et al. 1989).  Despite this, it is important to note that there is no evidence of EBV infection in many HL patients, so the exact role infectious agents and particularly EBV plays in development of the disease remains unclear and requires continued investigation (Böll, Borchmann, and Diehl 2010) (Weiss et al. 1987).

Individuals with HIV or at risk of AIDS have a significant increased risk of HL; however, this relationship does not hold among people with HIV/AIDS in Africa. Furthermore, among intravenous drug users who also have HIV, they too have more of a chance of developing HL. Other viruses such as the herpes virus 6 (HHV-6) have also showed associations with HL but study results are inconclusive (Lacroix et al. 2007).

Numerous human leukocyte antigens (HLA) types have been modestly associated with an increased risk of HL. HLA’s are the unique set of proteins, which are present on each individual’s cells and permit the immune system to recognize ‘self’ from ‘foreign’. This association is found in both cases of families and ‘isolated’ individuals. Lack of HLA class II expression has been associated with a poor prognosis, independent of other known prognostic factors (Diepstra et al. 2005). In general, there is a significant familial association of HL but no specific genes explaining this finding are currently identified (Goldin et al. 2005).

Research into the association of many types of individual cancers and socio-economic status (SES) is reported throughout in the literature. Regarding HL, the results are conflicting and knowing if a true relationship exists between SES and HL is difficult to discern. The most compelling evidence for such a relationship exists among the youngest (both children and young adults) individuals with HL, where those among the higher SES groups were at an increased risk for HL (Alexander et al. 1991). Similar results from Glaser et al., 2002 also showed young adults from higher socioeconomic classes are at even greater risk than their contemporaries from lower socioeconomic classes; this is particularly true of the nodular sclerosis subtype (Glaser et al. 2002).  Conversely, among older adults the results are mixed where either no association at all was found or there was a higher risk of HL among lower SES groups. This finding is in line with other research in the area of cancer in general where an increased risk of cancer is associated with lower SES (Cartwright and Watkins 2004).