US-born Latinas at great risk of having babies with retinoblastoma
In a large epidemiologic study, researchers at UCLA’s Jonsson Cancer Center found that the children of U.S.-born Latina women are at higher risk of having retinoblastoma, a malignant tumor of the retina which typically occurs in children under six.
The study, which focused on babies born in California, also found that offspring of older fathers were at greater risk for retinoblastoma, as were children born to women with sexually transmitted diseases and those born in multiple births, which may indicate an increased risk from in vitro fertilization. Those findings confirmed the results of several smaller studies.
The research team used data from the California Cancer Registry and examined all retinoblastoma cases reported from 1988 to 2007, said Julia Heck, the study’s first author and an assistant researcher in the UCLA Fielding School of Public Health. Using California data allowed the researchers to cull information from a large and diverse population that included many Latinas.
The study appears in the early online edition of the journal Cancer Causes & Control.
“One of the most interesting things we found in this study that hasn’t been reported is the differences among Latina mothers and the risk being lower among mothers born in Mexico,” Heck said. “We believe this is because women born in Mexico who come to the United States and have children have very healthy behaviors in the perinatal period, immediately before and after giving birth.”
Study senior author Dr. Beate Ritz, a Jonsson Cancer Center researcher and professor and chair of epidemiology and professor of environmental health sciences in the Fielding School, said Latinas born in the U.S. are less likely to exhibit the healthy pregnancy behaviors found in foreign-born Latinas. For example, they have poorer diets and are more likely to smoke and drink during pregnancy, which could contribute to the risks of retinoblastoma.
Do we know what causes retinoblastoma?
Retinoblastoma is caused by mutations (changes) in certain genes. Over the past few decades, scientists have made great progress in understanding how certain changes in a person’s DNA can cause cells of the retina to become cancerous. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects much more than the way we look.
Some genes have instructions that control when our cells grow, divide, and die. Certain genes that speed up cell division are called oncogenes. Others that slow down cell division, or cause cells to die at the right time, are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.
The most important gene involved in retinoblastoma is the RB1 tumor suppressor gene. This gene makes a protein (pRb) that helps stop cells from growing too quickly. Each cell normally has 2 RB1 genes. As long as a retinal cell has at least one RB1 gene that works as it should, it will not form a retinoblastoma. But when both of the RB1 genes are mutated or missing, a cell can grow unchecked. This can lead to further gene changes, which in turn may cause cells to become cancerous.
“Compared to U.S.-born Latinas, immigrant women born in rural Mexico often have even less education and lower socioeconomic status, but they retain healthier diets and perinatal habits, which may be correlated to lower risk of disease in their children,” Ritz said.
Hereditary or bilateral retinoblastoma
About 1 out of 4 children with retinoblastoma have a germline mutation in one RB1 gene; that is, all the cells in the body have the defective RB1 gene. The majority of these children (75%) have developed this mutation after conception while in the womb The other 25% have inherited it from one of the parents.
About 90% of children who are born with this germline mutation of the RB1 gene develop a retinoblastoma in one or both eyes. This happens when the second RB1 gene is lost or mutated.
Every person has 2 RB1 genes but passes only 1 on to each of their children (the other RB1 gene comes from the other parent). The odds that a parent with bilateral retinoblastoma will pass the mutated gene on to his or her child are 1 out of 2.
Most children with bilateral retinoblastoma don’t have an affected parent (the RB1 mutation occurs while in the womb). But these children will eventually be at risk of passing the disease on to their children. This is why we call this bilateral or congenital form of retinoblastoma “hereditary” (even though neither of the child’s parents may have been affected).
The team chose to study retinoblastoma because its causes remain poorly understood. They sought to examine associations between perinatal factors and cancer risk in California children. They identified 609 retinoblastoma cases, 420 that occurred in one eye (unilateral) and 187 that occurred in both eyes (bilateral). They randomly selected more than 200,000 control children without cancer from the California birth rolls. The source of most of the risk factor data in this study was information from birth certificates, Ritz said.
Retinoblastoma is the result of the loss or mutation of both alleles of the RB1 tumor suppressor gene. About 40 percent of cases are considered hereditary, and most of these present as bilateral disease.
Currently, the only known cause of retinoblastoma is a genetic mutation (change). This genetic form of retinoblastoma accounts for about 40% of cases and always occurs in very young children (rarely older than one year). When retinoblastoma affects both eyes, it is always a genetic condition. Despite the genetic link, only 10% to 15% of children with retinoblastoma have a family history of the disease. Rarely, the genetic form occurs in only one eye.
Children who have had bilateral retinoblastoma or the hereditary form of unilateral retinoblastoma are at increased risk for developing other types of cancer; the risk of additional tumors is higher for children who receive radiation therapy to the orbit (eye socket) to preserve vision or to other parts of the body where the tumor has spread. If a newborn has a family history of retinoblastoma, the baby should be examined shortly after birth by an ophthalmologist (a medical doctor who specializes in eye care) who is experienced in treating cancers of the eye.
About 60% of children with retinoblastoma do not have the genetic form. They develop a single tumor in only one eye, and they have no increased risk of additional tumors later in life.
“In conclusion, we observed risk of retinoblastoma to be related to several risk factors,” the study states. “Bilateral disease risk was higher among children of older fathers, and among children of multiple birth pregnancies. We observed a higher risk of unilateral disease among children of U.S.-born Latina women. Further research should be done to confirm this finding and to examine the unique risks experienced in this population.”
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The study was funded by the National Institutes of Health’s National Institute of Environmental Health Sciences (R21 ES018960 and R21 ES019986.
UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2012, the Jonsson Cancer Center was once again named among the nation’s top 10 cancer centers by U.S. News & World Report, a ranking it has held for 12 of the last 13 years.
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Kim Irwin
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University of California - Los Angeles Health Sciences