Crowded street

Photo by Pavel Novak

VIENNA—Living in overcrowded conditions may affect a young person’s risk of developing certain subtypes of Hodgkin lymphoma (HL), according to researchers.

They studied more than 600 children and young adults with HL in England and found that patients who lived in areas with more overcrowded households had a lower incidence of nodular sclerosis (NS) HL but a higher incidence of the not-otherwise-specified (NOS) subtype of HL.

“Our findings related to the NS subtype may suggest that the recurrent infections to which children living in overcrowded conditions are likely to have been exposed stimulate their immune systems and, hence, protect them against developing this type of cancer later in their childhood and early adult life,” said Richard McNally, PhD, of Newcastle University in the UK.

“Those who have a genetic susceptibility to HL and have been less exposed to infection through not living in such overcrowded conditions may have less developed immune systems as a result and are therefore at greater risk of developing this subtype.”

Dr McNally and his colleagues added that it’s more difficult to interpret the findings in the NOS group because this subtype of HL is very heterogeneous. The team said the role of chance cannot be ruled out.

They presented this research at the 2015 European Cancer Congress (abstract 1414).

Dr McNally and his colleagues wanted to gain a better understanding of factors that cause HL, so they analyzed a cohort of young HL patients in Northern England, looking at factors such as sex, age, and socio-economic deprivation.

The researchers evaluated 621 cases of HL recorded in the Northern Region Young Persons’ Malignant Disease Registry. Patients were ages 0 to 24 at diagnosis and were diagnosed between 1968 and 2003.

There were 5 different subtypes of HL in this group:

247 cases of the NS type

143 NOS

105 of mixed cellularity

58 lymphocyte-rich cases

68 “others.”

Age and sex

Overall, more males than females had HL, but the male-female ratio varied by both age group and subtype. The age-standardized rate (ASR) of HL for males was 18.15 per million persons per year, and the ASR for females was 10.52 per million persons per year.

For the NS subtype, there were 130 males and 117 females, but this was reversed at ages 20 to 24, with 72 females and 55 males. The ASR for NS HL at 20 to 24 was 14.26 for males and 18.79 for females.

“That this change takes place after puberty seems to suggest that estrogens may be responsible in some way,” Dr McNally said. “There are a lot of genes directly regulated by sex hormones, and they are obvious suspects. Alternatively, epigenetic changes . . . influencing key genes, induced by sex hormones, may be responsible.”

Overcrowding

The researchers calculated socio-economic deprivation using the 4 components of the Townsend deprivation score: household overcrowding, non-home ownership, unemployment, and households with no car.

They observed a lower incidence of NS HL among those patients living in areas with more overcrowded households. The relative risk of NS HL was 0.88 for a 1% increase in household overcrowding (P<0.001).

For the NOS subtype, the reverse was seen. A 1% increase in household overcrowding was associated with an increased incidence of NOS HL—a relative risk of 1.17.

Overcrowding seemed to have no effect on the incidence of mixed-cellularity HL or lymphocyte-rich HL.

“We knew already that recurrent infections may protect against childhood leukemia, and now it looks as we can add Hodgkin lymphoma and, particularly its NS subtype, to the list,” Dr McNally said. “In order to further investigate the factors involved, prospective studies should investigate the hormonal changes and recurrent infections and their direct link to the risk of lymphoma, but such studies are difficult to do in rare diseases.”

“A practical follow-up would be case-control studies examining biological markers related to exposure to a multitude of infectious agents, and indeed to hormonal status itself, while genetic studies are another possibility.”

Living conditions linked to risk of Hodgkin lymphoma