Thursday, December 04, 2008

European ancestry associated with higher breast cancer risk?

Latinas have been found to have a lower incidence of breast cancer than other ethnic groups. Indigenous Americans have the lowest incidence. This meta-review paper from a few months ago finds that ethnic disparities in breast cancer can be explained by SES, except for the lower incidence among African Americans.

So what do they find in this new paper (see abstract below)? It's a case control study with a pretty large sample size (440 cases and 597 controls, matched for age) of Latinas in the SF Bay area to determine whether genetic differences between groups account for differences in breast cancer incidence. They used 106 AIMs (ancestry informative markers). Interestingly:
"Breast cancer among Latinas presents a particularly
interesting case because the main ancestral components of the Latino population (European and Indigenous American) have the highest and lowest breast cancer incidence (1)."
They control for a suite of known breast cancer risk factors
(including education, but unfortunately, not income). Surprisingly the cases and controls differed significantly for many of the measured risk factors.

The main findings:
"In unadjusted models, we found a strong association between genetic ancestry (continuous) and breast cancer risk. Higher European ancestry was associated with increased risk, with an odds ratio (OR) of 1.79 [95% confidence intervals (95% CI), 1.28–2.79; P less than 0.001] for every 25% increase in European ancestry. When known risk factors and place of birth were adjusted for (Table 2), the association with European ancestry was somewhat attenuated but remained statistically significant (OR, 1.39; 95% CI, 1.06–2.11; P = 0.013). When African ancestry was included in the adjusted model, the association with European ancestry became stronger [OR for European ancestry, 1.54 (95% CI, 1.11–2.52; P = 0.004), and OR for African ancestry, 2.05 (95% CI, 1.00–7.56; P = 0.055)]."
They also looked at the association using genetic admixture and "using parent/grandparent European origin instead of genetic ancestry."
"We observed a significant association between the number of European-born parents/grandparents and breast cancer risk, with higher number of European ancestors being associated with increased risk (OR, 1.21; 95% CI, 1.02–1.44; P = 0.025, adjusted model)."
Although their results suggest that there may be some genetic risk factor specific to individuals with higher European ancestry, they are careful to acknowledge the possibility for residual confounders. It's too bad they didn't control for income and/or some other SES variables.

Genetic Ancestry and Risk of Breast Cancer among U.S. Latinas
Laura Fejerman, Esther M. John, Scott Huntsman, Kenny Beckman, Shweta Choudhry, Eliseo Perez-Stable, Esteban González Burchard and Elad Ziv
Cancer Research 2008;68(23):9723–8
Abstract: U.S. Latinas have a lower incidence of breast cancer compared with non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic ancestry from Europeans and Indigenous Americans. We used genetic markers to estimate the ancestry of Latina breast cancer cases and controls and assessed the association with genetic ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 ancestry informative markers in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco Bay area and estimated genetic ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (95% CI) for ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European ancestry was associated with increased breast cancer risk. The OR for a 25% increase in European ancestry was 1.79 (95% CI, 1.28–2.79; P less than 0.001). When known risk factors and place of birth were adjusted for, the association with European ancestry was attenuated but remained statistically significant (OR, 1.39; 95% CI, 1.06–2.11; P = 0.013). Further work is needed to determine if the association is due to genetic differences between populations or possibly due to environmental factors not measured.


Maju said...

Among risk factors, did they test for breastfeeding and age of earliest childbirth? I understand that no breatsfeeding and late birthgiving are major risk factors that can vary a lot through cultural (rather than merely genetic) groups.

Maju said...

Another cultural factor may be frequency of screening: apparently many breast cancers now detected would probably vanish on their own without any treatment. It's possible that white women tend to visit their gynecologist much more often than other groups.

Yann Klimentidis said...

They did control for duration of breastfeeding, but not for age at giving birth, as far as I can tell.
As for frequency of screening, they don't look at that either. I think these could be important biases given that their controls are from the general population. (i.e. not from a breast cancer screening place or hospital) and the degree of European ancestry was significantly higher on average among the cases than controls.

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