Inbreeding of first cousins puts younger Arabs, Druze at risk for cancer

Science and Health

There is a high prevalence of colorectal cancer due to hereditary polyposis syndrome among Arabs and Druze in the north of the country. According to a new study by researchers at the Rambam Healthcare Campus in Haifa, the condition is caused by consanguinity – inbreeding of first cousins.

The findings have been published under the title “High prevalence of MUTYH associated polyposis among minority populations in Israel, due to rare founder pathogenic variants” in the international journal Digestive and Liver Disease.

The study showed that mutations in the MUTYH gene associated with the hereditary syndrome MUTYH-associated polyposis (MAP syndrome for short) cause about 27% of the cases of polyposis patients in the Arab and Druze populations in the north.

“This is a finding of great importance for the relevant population,” the researchers said, as “the information will make it possible to locate families who are at increased risk of colon cancer and to adapt follow-up and prevention programs to them.”

Colon cancer, the second-most common cancer in Israel

Cancer Immunotherapy by NIH Image Gallery. (credit: FLICKR)

Colorectal cancer is the second-most-common cancer, with some 3,000 new patients diagnosed in Israel each year, according to the Israel Cancer Association (ICA). It is also the second-most-common cause of death among all cancer deaths, regardless of gender, in Jews and Arabs.

Colon cancer begins with polyps (benign, pre-cancerous growths) that develop in the colon,” explained Dr. Elizabeth Half, director of the unit for the detection and prevention of gastrointestinal malignancies and of the multidisciplinary center for early detection and prevention of cancer at Rambam, who led the study with Gili Reznik Levi.

“Gastroenterological follow-up and colonoscopy tests make it possible to detect polyps in the pre-cancerous stage and remove them if possible or refer the patient to surgery, thus preventing the development of cancer. These processes translate into saving lives in high percentages,” she added.

Gili Reznik-Levi, a senior genetic counselor who is in charge of the field of oncogenetics at Rambam’s Genetics Institute, said that between 10% to 20% of colon cancer cases are due to a hereditary genetic background. Conditions associated with multiple polyps in the colon raise the suspicion of a mutation in another of the genes associated with hereditary syndromes.

“One of these syndromes is the MAP syndrome,” continued Reznik- Levi. “The uniqueness of this syndrome compared to other hereditary cancer syndromes is the form of inheritance. This syndrome is inherited in an autosomal recessive manner, meaning that mutations are required in both copies of the gene (one from the mother and one from the father) for it to be expressed.

The risk of hereditary conditions in this inheritance increases significantly when there is a close genetic relationship between the parents.”

According to Dr. Karin Weiss, director of Rambam’s Genetics Institute, the syndrome accounts for about six percent of colon cancer cases at a young age, when the scientific and medical community has known for many years that mutations in this gene are common in the European population, as well as in the Jewish population of North African origin in Israel.

However, so far no research has been carried out on this syndrome among Israel’s Arab population. “Our assessment was that, in light of a relatively high rate of consanguineous marriages, we found a high prevalence of this syndrome in the population treated at Rambam – that is, in the Arab and Druze population in the Galilee,” Weiss said.

Indeed, this is what emerged from the results of the study – out of 37 patients with polyposis with or without colon cancer from 30 different families, eight families (27%) had bi-allelic mutations (mutations in both copies) of the MUTYH gene.

“We also collaborated with four other medical centers that treat polyposis patients – the Rabin Medical Center in Petah Tikva, Hadassah-University Medical Center in Jerusalem, Soroka-University Medical Center in Beersheba and Sheba Medical Center at Tel Hashomer – and together we collected the genetic information on patients with MAP syndrome from the Arab sector in Israel,” added Reznik-Levi.

“The findings are unique, because the mutations found in these families are different from the mutations known in the general population and the Israeli Jewish population. In addition, we saw that in these families, the age of colon cancer incidence was really young – an average age of 38 years – which is 10 years younger compared to what is reported in the medical literature among families with MAP syndrome.”

Another important finding is that there is one particular mutation that is responsible for most of the cases in these families. “This makes it possible to carry out an easy, accurate, quick and cheap genetic diagnosis to locate individuals with MAP syndrome in this population,” Weiss noted. “Diagnosis of the first individual in the family makes it possible to assess the risk of the syndrome and the high risk of cancer in other relatives as well.”

However, while the results of the study shed light on the processes by which the disease developed among certain risk groups, the main importance is in the follow-up and early detection processes. “Patients with MAP syndrome who do not perform the necessary follow-up colonoscopy have a very high risk of up to 80% of developing colon cancer during their lifetime,” Half said. “This risk can be avoided if regular colonoscopy examinations are performed at a young age, starting at age 20 to 25 years.”

According to the researchers’ assessment, in some villages in the Galilee region there is, apparently, a high prevalence of MAP syndrome. “The next step of the research will be to check the prevalence of MUTYH in these villages among healthy individuals. If a high prevalence is found, it may be appropriate to offer genetic testing to the entire adult population in the villages at risk.

“It’s important for us to have awareness of this syndrome in the Arab and Druze population of the Galilee that is at risk. The general practitioners and gastroenterologists who are tasked with following the warning signs must refer the relevant patients to genetic counseling for early detection and even the prevention of cancer,” the team concluded.