Holocaust survivors face greater cancer risk

Holocaust survivors exposed to a variety of severe deprivations demonstrated a small, but consistent, increase in cancer risk, according to results of a nationwide cohort study conducted in Israel.

“The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II,” Siegal Sadetzki, MD, MPH, head of the cancer and radiation epidemiology unit of the Gertner Institute at Chaim Sheba Medical Center in Israel, said in a press release. “Such inspection cannot be conducted by experimental studies and could only be evaluated by using observational epidemiological surveys.”

Sadetzki and colleagues evaluated whether conditions that Holocaust survivors faced — such as starvation, overcrowding, infectious diseases and psychological stress — might have influenced their risk for cancer.

The analysis included data from 152,622 Holocaust survivors (51.1% men; mean age at the end of follow-up, 76.1 years).

Researchers categorized the survivors into four groups:

Group A (n = 81,927): Israeli Jews who were stateless refugees under the occupation of Nazi Germany who applied for and received compensation under the “Victims of Nazi Persecution Act” and were suffering from at least 25% disability;

Group B (n = 26,491): those who lived in concentration or work camps for at least 6 months or who hid or lived in a ghetto under a false identity for at least 18 months, entitled for compensation under the “Holocaust Survivors’ Benefits Act;”

Disabled war veterans (n = 14,173): those who served as soldiers between 1939 and 1945 in the allied armies, partisans or the Red Army and had at least 10% health disability; and

Denied compensation group (n = 10,031): those who applied as Holocaust victims but were ineligible for compensation.

The primary analysis compared the first three groups with the group denied compensation.

A greater proportion of those eligible for compensation received a cancer diagnosis than those denied compensation (22.2% vs. 16%; P < .0001).

Analyses adjusted for birth cohort, sex, country of origin and period of immigration showed the total granted compensation group had a slightly higher risk for cancer than the noncompensated group (HR = 1.06; 95% CI, 1.05-1.08). This increase appeared driven by the greater risk among disabled war veterans (HR = 1.53; 95% CI, 1.42-1.64) and those in group A (HR = 1.1; 95% CI, 1.04-1.16), whereas those in group B did not have a significantly increased risk when evaluated separately.

An analysis by tumor site showed greater risks for cancers of the colon/rectum (HR = 1.12; 95% CI, 0.99-1.27) and lung (HR = 1.37; 95% CI, 1.09-1.72) in the compensated vs. noncompensated groups.

The risk for cancer in the compensated group appeared higher among men (HR = 1.07; 95% CI, 1.06-1.09) than women (HR = 1.02; 95% CI, 1-1.04).

As a complementary analysis, researchers also compared survivors born in countries governed by Nazi Germany (n = 91,929) with survivors born in nonoccupied countries (n = 50,208).

Those in the occupied countries group showed a greater cancer risk (HR = 1.08; 95% CI, 1.05-1.1). This risk also appeared greater among men (HR = 1.1; 95% CI, 1.06-1.14) than women (HR = 1.05; 95% CI, 1.02-1.09).

The tumor site analysis for these two groups showed the occupied countries cohort had greater risks for prostate, pancreas (men), thyroid, kidney, liver, cervix and stomach (men) cancers, as well as for chronic leukemia.

Researchers noted that they derived the definition of exposure from files created for legal purposes or based it from the country of origin, which could lead to misclassification. Further, they had no data on the degree of various exposures, so could not evaluate a dose–response effect.

Still, this is the largest and most comprehensive observational study evaluating cancer risk in this population, according to the researchers.

“The consistency of our results observed in both men and women and in the two different approaches supports the association between being a Holocaust survivor and an increase risk for developing colorectal and lung cancers,” Sadetzki and colleagues wrote. “The findings emphasize the complexity of the etiology of cancer development and the difficulties in determining the role of individual risk factors in the face of simultaneous exposures.”

Although the emotional and physical stressors experienced by Holocaust survivors exceed those of victims of other environmental exposures, there are some similarities between Holocaust stressors and those experienced by underserved minority groups today, Beti Thompson, PhD, of Fred Hutchinson Cancer Research Center and University of Washington, and colleagues wrote in a related editorial.

“Racial and ethnic minorities in the United States are disproportionately exposed to social stressors like neighborhood violence,” Thompson and colleagues wrote.

For instance, research has shown that 87.2% of randomly selected black individuals experienced at least one traumatic event — such as assaultive violence — during their lifetimes, and another report showed black breast cancer survivors living in predominantly black neighborhoods in Chicago had higher rates of sexual abuse during childhood and adolescence, feelings of loneliness and depression than other survivors.

Further, researchers have suggested that biobehavioral risk factors, like poverty and racial discrimination, can trigger norepinephrine or epinephrine and cortisol, which can dampen immune responses and perturb homeostasis to hasten cancer progression.

“Sadetzki and colleagues’ findings suggest an association between the dreadful experiences of Holocaust survivors and cancer incidence,” Thompson and colleagues wrote. “We observe a parallel with the disproportionate exposure to stressors at the neighborhood and community level experienced by some racial minorities in the United States. Although the body of knowledge to support this link has grown in the past decade, additional research is needed from teams of social, behavioral, and biologic scientists working to untangle these complex phenomena.” – by Alexandra Todak

Disclosure: One researcher reports personal fees from the special committee nominated to assess the causal association between the period of persecution by the Nazis and cancer incidence during the study. The other researchers and editorial authors report no relevant financial disclosures.