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Srdjan Denic

Publications and source records attributed to Srdjan Denic.

5 recordsLinked to original sources
PubMed2005

Incestuous gene in consanguinophilia and incest: toward a consilience theory of incest taboo.

Westermarck's theory of incest taboo states that inhibition of sexual attraction between biologically close relatives is situational and develops during co-residence in early childhood. By contrast, the biological (genetic) basis of incest taboo is presumed from its universality in all human societies and animals and teleologically, from the need to prevent the detrimental effects of inbreeding. As incest taboo violation is infrequent, the frequency of the presumed gene in the population is believed to be near 100%. We present arguments which suggest that the incestuous gene may exist in all populations and could play an important role in evolution. When malaria emerged 10,000 years ago, human adaptation proceeded by the selection of protective genotypes. Among them, homozygotes for alpha-thalassemia, hemoglobin C, and Duffy antigen negative blood group, have better survival odds in malarious regions than heterozygotes and those with normal genotypes. Since consanguinity increases homozygosity, it increases the number of persons who are resistant to malaria. To pro-create, however, biologically close individuals must not feel sexual aversion that normally develops between those who spend their early childhood together (Westermarck effect). It is reasonable to assume, therefore, that mutation of the gene that discourages inbreeding may have appeared at an early time in evolution, and produced a weak Westermarck effect. This gene (we will call it anti-w) failed to inhibit mating between kins. Inbred offspring of anti-w carriers, would statistically, more likely carry both anti-w and homozygote genotypes which increase fitness in the presence of malaria. Today, alpha-thalassemia is the single most common monogenetic disorders in man with over 500 millions carriers concentrated in malarious regions of the world. The world's consanguineous population is some 500-800 millions and is also concentrated in malarious regions. Population migration has spread the gene outside areas of high malaria endemicity. However, endemicity of malaria provides a worldwide gradient of genotype frequencies which makes the incestuous gene hypothesis testable. We propose that the incestuous anti-w allele was co-selected with some of the genes protective against malaria because anti-w facilitates mating between genetically close individuals whose offspring better survive malaria.

Consanguinity↗
PubMed2005

Parental consanguinity and risk of breast cancer: a population-based case-control study.

BACKGROUND: An estimated 600 million people in the world have consanguineous parents. The effect of consanguinity on the risk of breast cancer is uncertain. The objective of this case-control study was to examine whether parental consanguinity and different levels of inbreeding affect the risk and pathology characteristics of breast cancer. MATERIAL/METHODS: Over a 36-month period, consecutive female breast cancer patients were recruited in the main cancer hospital in the United Arab Emirates. All were locally born Arabs with a tissue diagnosis of breast cancer. The controls were locally born Arabs without breast cancer matched to cases by sex, age, and residence. The coefficient of inbreeding (F) of both groups was determined from information they provided about their parents' kinship. RESULTS: The mean age of the 72 patients and 187 controls was 48.6 years (range: 25-86) and 48.5 years (range: 25-82), respectively (P = 0.46). Consanguinity rates of the patients and controls were 29.2% and 28.9% (P = 0.96) and the coefficients of inbreeding were 0.0117 and 0.0167 (P = 0.21), respectively. More closely inbred women (F > or = 0.0625) were less frequent among patients than controls, but the difference was not statistically significant (P = 0.12). The rates of pathological stage of disease, tumor histologies, and tumor grades were similar between more and less inbred patients. CONCLUSIONS: Parental consanguinity in Arabs, even when a marriage is between first cousins or double first cousins, was not associated with an altered risk of breast cancer.

Adult↗
PubMed2004

Quality of age data in patients from developing countries.

BACKGROUND: Age misreporting is common in demographic studies but the prevalence and magnitude of age misreporting in clinical cohorts is unknown. We analysed single-year age distribution and terminal digit preference in cancer patients from developing countries. METHOD: Age distribution was analysed by plotting a single-year age of 3874 cancer patients from 72 different countries, mainly from the Indian subcontinent and the Middle East, who resided in the UAE at the time of cancer diagnosis. Preference for age ending with digits '0' and '5' was evaluated using Whipple's index (WI), which has value 100 in cohorts without preference. Preference for all 10 terminal digits was expressed as the difference between the found and expected frequencies using Myers blended method and was graphed. RESULTS: Age data quality was low in cancer patients from the Indian subcontinent (WI = 177) and Middle Eastern countries (WI = 113-204). Females of all nationalities supplied better quality of age data (lower WI) than males. Preference for age ending with digits '0' and '5' was found in all populations except the UAE male citizens who did not show preference for terminal digit '0'. CONCLUSION: Age data quality in this cohort of patients from developing countries was low. Preference for age ending with numbers '0' and '5' is common. In studies conducted in developing countries, age data quality should be analysed as it may bias results and weaken the power of the study.

Age Distribution↗
PubMed2002

Breast cancer, consanguinity, and lethal tumor genes: simulation of BRCA1/2 prevalence over 40 generations.

Marriage between biological relatives is a social custom with a long history in many parts of the world. Today, hundreds of millions of individuals live in consanguineous families. The offspring of consanguineous parents are more likely to have the same two alleles (homozygosity) by descent. In consanguineous family with BRCA1/2 gene mutations, an offspring is more likely to be BRCA1/2 homozygous. The consequences of BRCA1/2 mutation homozygosity in humans are unknown. In knockout mice, BRCA1 or BRCA2 homozygotes die as embryos. Because tumor suppressor genes are conserved and less species-specific than other genes, human BRCA1/2 homozygotes are likely to be biologically non-viable and are unknown to exist. Among the conceptuses of consanguineous couples, there are excess deaths (abortions, stillbirths, perinatal and early-childhood deaths) as well as a decreased risk of breast cancer, especially in younger females. It has been suggested that, in part, the excess deaths are due to BRCA1/2 and other still undiscovered tumor gene homozygotes. To examine the consequences of the long-term practice of consanguineous marriage on the prevalence of lethal cancer genes, we simulated, by computer, the mating of non-consanguineous and consanguineous populations over 40 generations. The program was developed in Basic for a Macintosh computer. The input comprised the rates of consanguineous marriage types and the output parameter was the rate of heterozygotes (carriers) in each generation. The combined prevalence of BRCA1/2 mutation of 1% was used as a starting reference point. Absence of spontaneous mutations and gene flow were assumed. In a randomly mating population, the BRCA1/2 carrier rate decreases on average 0.0035% every 25 years. In a highly consanguineous population, the carrier rate decreases on average 0.022% every 25 years, or six times faster than in a non-consanguineous population. There is a worldwide trend of decreasing breast cancer incidence with an increasing consanguinity rate. In conclusion, the BRCA1/2 and possibly other undiscovered tumor gene carrier rates are significantly lower in consanguineous than in non-consanguineous populations. Gene frequency in a population depends on the rate of inbreeding and length of consanguineous practices. A drift phenomenon may exert a major effect on the carrier rate. Consanguinity may explain part of the worldwide variation of breast cancer incidence.

Breast Neoplasms↗