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Genetics, society and race

Genetics, society and race
Minority individuals are much more likely to develop and die from cancer than the general U.S. population. Prior research points to lack of health insurance, poverty, language and cultural barriers, and inadequate access to early detection services and good medical care as causes. Research reported today at the 2007 Annual Meeting of the American Association for Cancer Research (AACR) suggests that genetics, in addition to socioeconomic status, are important factors accounting for the disparity of cancer incidence and mortality between African-Americans, Hispanics and Caucasians.

Exploring New Measures of Socio-Demographic Factors Linked to Later Stage of Cancer Diagnosis: Abstract 795
A survey of stomach and kidney cancer patients in Los Angeles revealed that those who were diagnosed in a late stage of disease when cancer is harder to treat successfully were likely to be older, living in an unsafe neighborhood and traveling at least 45 minutes to get to the doctor.

Scientists at the University of Southern California's Keck School of Medicine cite two general types of personal risk factors linked to late cancer diagnosis: socio-economic, or cultural, factors correlation to knowledge about the health care system and difficulties accessing it; and individuals' failure to give priority to medical care, despite having access to it.

While minorities have been shown to have higher rates of dying from cancer, it hasn't always been clear why, said Ann Hamilton, Ph.D., assistant professor of preventive medicine at USC. Using proportions of minorities in census tracts or income and education statistics hasn't been totally effective in identifying subgroups at higher risk.

Hamilton and USC colleague Myles Cockburn mailed a questionnaire to patients diagnosed with stomach and kidney cancer between 2000 and 2001 in Los Angeles County, which has a large Hispanic population. It asked about, among other things, access to care, acculturation, neighborhood environment, other diseases and demographic information. The acculturation scale was based on a series of questions, such as, What language do you speak primarily at home English, Spanish or both?'.

Hamilton and Cockburn also wanted to identify "neighborhood-related" factors that could help predict population subgroups at higher risk for being diagnosed late, in addition to personal risk factors. "I wanted to identify new combinations of individual risk factors as well as ecological factors at the census tract level that could be used to better predict subgroups at higher risk," Hamilton said.

The scientists observed that, at the census tract level, the percentage of people who speak a language other than English at home, the percentage of Hispanics 25 or older with less than a ninth grade education, percent unemployed and percent using public transportation were correlated with a higher percentage of cancers being diagnosed at a later stage.

"In using both ecological and personal measures, we were trying to determine how both factors may increase risk. We were assessing the effect of personal risk factors in the context of the neighborhood environment," Hamilton said. "For example, we found an indication that after taking other factors into account, a person with a lower level of acculturation who lived in an area where few others speak English was more likely to be diagnosed at a later stage of disease than the same type of person who lived in an area where most spoke English".

The results, Hamilton said, may help better target disease intervention programs for those most vulnerable and at risk.

The Effect of Hospital and Clinician Volume on Racial Differences in Disease Recurrence Following Surgery for Prostate Cancer: Abstract 3416
Epidemiologists have unexpectedly observed that African Americans had a higher rate of recurrence following prostate cancer surgery than did whites, regardless of whether or not patients received surgery at hospitals or by surgeons who performed a high number of such operations.

The findings were surprising as prior research has shown that, in general, patients fare better at hospitals that perform a high volume of surgeries or by surgeons who perform a large number of operations.

As per epidemiologist Kyna Gooden, Ph.D., of Shaw University, prior studies have shown that African Americans have a higher rate of prostate cancer recurrence and a greater likelihood of dying from their cancer following prostate surgery more specifically, total removal of the prostate gland in comparison to white men.

She and her co-researchers at Shaw University and the University of North Carolina in Chapel Hill, looked at whether the number of prostate cancer surgeries a hospital or a surgeon performed affected this disparity.

Gooden and her team hypothesized that a disproportionate number of African Americans were treated at hospitals or by physicians performing fewer surgeries. The racial differences in the prostate cancer recurrence and mortality following surgery would disappear, they assumed, once they took into account hospital and doctor volume.

They examined data from the Surveillance, Epidemiology, and End-Results Medicare database for 962 African American and 7,387 white men diagnosed with prostate cancer between 1993 and 1999 who had received surgery within six months of diagnosis. They controlled for age at diagnosis, cancer stage and grade.

When the scientists looked at the outcomes after surgery in relation to volume, results were similar to prior findings patients who had surgery at high volume hospitals for prostate cancer were less likely to have cancers that returned and less likely to die from prostate cancer. But when they broke down the numbers by race for African Americans and whites, they observed that surprisingly, the racial disparities persisted.

"Even for patients who went to high volume hospitals and were seen by high volume physicians, there was still a racial disparity," Gooden said. "We expected that if everyone was treated by similarly experienced doctors or hospitals, they would have had comparable outcomes. But that wasn't the case".

"These results may have less to do with access to clinical care but more to do with lifestyle factors and the physical and genetic characteristics of the tumor itself," Gooden said.

Differential Gene Expression in Normal Breast Tissue from African American and Caucasian Women: Abstract 43
In preliminary findings, scientists have identified differences in the expression of two genes in normal breast tissue from African American and white women that could predispose the former to develop more aggressive tumors and poorer prognoses.

Postdoctoral fellow Lori Field, Ph.D., of the Windber Research Institute, and his colleagues at Walter Reed Army Medical Center and Invitrogen Informatics, wanted to understand why breast cancer mortality rates are higher in African American women than in Caucasian, even though the overall incidence in white women is higher. Breast tumors in black women are larger, more aggressive, and more likely to spread to the lymph node than those in white women.

Before comparing breast cancer tumors, the researchers first examined healthy breast tissue. They obtained samples from 26 African American and 22 Caucasian women enrolled in the Clinical Breast Care Project, a federally mandated breast research program with both military and civilian centers.

Using microarray technology to examine large numbers of genes at once, they found differences in the expression of 89 genes among the two groups. Two of these genes PSPH, phosphoserine phosphatase, which is involved in forming serine, and ACSM1, acyl-CoA synthetase medium chain family member 1, which is involved in fatty acid oxidation had a higher expression in the African American women.

Serine is an intermediate in the synthesis of other amino acids, as well as DNA and lipids. If more serine is being shunted into any of these pathways, Field said, it might enhance cellular division and growth. Increased ACSM1 expression could increase the rate of fatty acid oxidation in the cell, resulting in a rise in cellular energy production.

"Both conditions could promote cell growth and could potentially provide greater growth advantage to breast cells in African Americans in comparison to Caucasians and could increase the likelihood to potential cancer transformation," Field said.

While the scientists continue to validate these initial findings, they currently are comparing breast tumors from African American and Caucasian women to look for differences in gene expression.

"If we see that there are differences in the breast tumors, we may find new molecular targets to which treatment can be tailored specifically to African American women," Field said.

Familial Breast Cancer in a Cohort of 59,000 African American Women: the Black Women's Health Study: Abstract 2500
Having a mother or sister with breast cancer significantly increases the risk for young African American women to develop breast cancer, as per the analysis of questionnaires answered by approximately 59,000 African American women enrolled in the Black Women's Health Study.

Beginning in 1995, questionnaires were given every two years to women none of whom knowingly had cancer asking about demographics, reproductive and health history, family history of breast cancer and other factors.

As per principal investigator Julie Palmer, ScD, professor of epidemiology at Boston University, few studies have examined the relationship of family history to breast cancer risk in African American women, and none have done so prospectively.

"We wanted to see if we would confirm what had been shown in white women that having a mother or sister with breast cancer would increase a woman's risk of developing breast cancer," Palmer said.

Analyzing 10 years' worth of follow-up questionnaires found there were 1,050 cases of breast cancer among those who completed questionnaires on family history. The team, observed that the incidence rate-ratio for such women was 1.77, meaning that overall, African American women who had a first degree relative either a mother or a sister with breast cancer had 1.77 times the risk of getting breast cancer in comparison to another woman of the same age who didn't have a family member with breast cancer. Having a family history of breast cancer was a stronger risk factor in women under 35, among whom the relative risk was 2.67.

Palmer said that as the study group ages and the number of women with cancer increases, the team can begin to examine other factors in cancer risk and development. "We'd expect that relative risk of 1.77 to go up quite a bit for women who have two first-degree relatives," she said. In fact, the scientists observed that the overall relative risk for breast cancer was 2.58 for having two or more first-degree relatives with breast cancer, but the figure was based on few women.

The scientists plan to examine whether having a family member with other cancers is correlation to heightened breast cancer risk. Palmer noted that ovary cancer might be one such cancer because "there are some shared genes," referring to the tumor suppressor gene BRCA1, which when damaged can increase a woman's risk of both breast and ovary cancers.

In time, Palmer said, the study will have data to report on other cancers, such as colon and lung.

Compromised Complement System Increases Colon Cancer Susceptibility in African Americans: Abstract 2507
Genetic variations in the body's immune system could play a role in making African Americans more susceptible to developing colon cancer, researchers have found.

Scientists led by Krista Zanetti, Ph.D., a postdoctoral fellow in the National Cancer.

Institute's Division of Cancer Prevention and Center for Cancer Research, looked at variations in genetic sequences of the gene that makes mannose-binding lectin (MBL), a protein that plays a role in inflammation and innate immunity. They compared 26 MBL variations, or single nucleotide polymorphisms (SNPs), in 261 patients with colon cancer and 537 normal controls in the Baltimore area.

Of the 26, four SNPs were linked to a significant increase in colon cancer risk in African Americans, though not in Caucasians. African Americans who carried two copies of all four variants had an approximately six-fold higher risk of colon cancer in comparison to those without such variants.

The four DNA variants occur in linkage disequilibrium that is, they appear together at a higher frequency than by random chance in both African Americans and Caucasians, though they are more prevalent in the former. "It was surprising," Zanetti said, "because we wouldn't necessarily assume that any one SNP would be associated with one race more than others. It wasn't our hypothesis".

Zanetti and her team currently are attempting to validate the findings with data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial, a randomized control trial originally designed to test the effectiveness of cancer screening methods. They will screen the colorectal cancer patient subset of the study for the four SNPs, with individuals with colorectal polyps as controls. Both of the latter groups are mostly Caucasian.

"Before we validate these associations in African Americans, we first need to know whether or not they exist in Caucasians that's the number one question we want to answer," Zanetti said. "Is it possible that this is actually an African American risk factor?".

As per Zanetti, the PLCO study gives the scientists the high level of power needed to detect whether these associations really exist in Caucasians. That would then enable the team to design the rest of their study.

Zanetti noted that over the past three decades colon cancer deaths in African Americans have generally been higher than in Caucasians. "We don't know why the decline in death rates has been smaller in African Americans, but we believe it's more than one factor," she said. "These SNPs aren't necessarily the only answer. We need to keep working to uncover all the contributors to this increased risk, whether there are underlying biological issues or social determinants.

"We're doing a multitude of functional studies in the laboratory to see if we can link a phenotype to the genotype we have found," she said. "We're trying to link it to biological function I think there's more to it than just association".

Posted by: Janet    Source

Did you know?
Minority individuals are much more likely to develop and die from cancer than the general U.S. population. Prior research points to lack of health insurance, poverty, language and cultural barriers, and inadequate access to early detection services and good medical care as causes. Research reported today at the 2007 Annual Meeting of the American Association for Cancer Research (AACR) suggests that genetics, in addition to socioeconomic status, are important factors accounting for the disparity of cancer incidence and mortality between African-Americans, Hispanics and Caucasians. Genetics, society and race

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