Circum-Mediterranean influence in the Y-chromosome lineages associated with prostate cancer in Mexican men: A Converso heritage founder effect?

Abstract

Prostate cancer is the second most common neoplasia amongst men worldwide. Hereditary susceptibility and ancestral heritage are well-established risk factors that explain the disparity trends across different ethnicities, populations, and regions even within the same country. The Y-chromosome has been considered a prototype biomarker for male health. African, European, Middle Eastern, and Hispanic ancestries exhibit the highest incidences of such neoplasia; Asians have the lowest rates. Nonetheless, the contribution of ancestry patterns has been scarcely explored among Latino males. The Mexican population has an extremely diverse genetic architecture where all the aforementioned ancestral backgrounds converge. Trans-ethnic research could illuminate the aetiology of prostate cancer, involving the migratory patterns, founder effects, and the ethnic contributions to its disparate incidence rates. The contribution of the ancestral heritage to prostate cancer risk were explored through a case-control study (152 cases and 372 controls) study in Mexican Mestizo males. Seventeen microsatellites were used to trace back the ancestral heritage using two Bayesian predictor methods. The lineage R1a seems to contribute to prostate cancer (ORadjusted:8.04, 95%CI:1.41-45.80) development, whereas E1b1a/E1b1b and GHIJ contributed to well-differentiated (Gleason ≤ 7), and late-onset prostate cancer. Meta-analyses reinforced our findings. The mentioned lineages exhibited a connection with the Middle Eastern and North African populations that enriched the patrilineal diversity to the southeast region of the Iberian Peninsula. This ancestral legacy arrived at the New World with the Spanish and Sephardim migrations. Our findings reinforced the contribution of family history and ethnic background to prostate cancer risk, although should be confirmed using a large sample size. Nonetheless, given its complex aetiology, in addition to the genetic component, the lifestyle and xenobiotic exposition could also influence the obtained results.