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Consanguinity as risk factor for cervical carcinoma
Medical Hypotheses (2003) 60(3), 321–324 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0306-9877(02)00389-4
Consanguinity as risk factor for cervical carcinoma S. Denic UAE University, Al Ain, United Arab Emirates
Summary Cervical carcinoma is caused by human papillomavirus (HPV). Among the risk factors for HPV infection are having multiple sex partners and sex partners who themselves had multiple sex partners. Women married to relatives are more likely to become infected with HPV and develop cervical carcinoma. Consanguineous spouses have a mild sexual aversion to each other that leads to sex avoidance and increases likelihood of satisfying sexual desire outside the marriage. Sexual aversion develops as a result of spouses growing together in early childhood, which triggers biological imprinting of Westermarck. Westermarck’s effect prevents incest in nuclear family. In consanguineous family, it extends to spouses, producing mild sexual antipathy. Because of high prevalence of consanguinity worldwide, it is important to test this hypothesis. ª 2003 Elsevier Science Ltd. All rights reserved.
INTRODUCTION Marriages between relatives are common worldwide and lead to human inbreeding. Their health consequences are primarily linked to the increased risk of congenital malformations and autosomal recessive diseases (1). In addition to genetic pressure, a consanguineous marriage, as a way of life, imposes an environmental pressure upon the family. Because development of malignant neoplasms is related to genetic and environmental factors, a possible causal relationship between consanguinity and cancer should be examined, especially since cancer is generally not linked with consanguinity. Whether consanguinity alters the risk of cancer is important to know because hundreds of millions of individuals live in consanguineous families. The prevalence of consanguineous marriages, out of all marriages, is less than 1% in the West, 1% in South America, 4% in
Received 3 April 2002 Accepted 12 July 2002 Correspondence to: S. Denic MD, Department of Medicine, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates. Phone: +971-3-7039-677; Fax: +971-3-7672-995; E-mail: [email protected]
Japan and 10–50% in the North Africa, Middle East, south-west and south Asia. In populous Indochina and China the frequency of consanguineous marriages varies, rising above 50% in some segments of their populations (2). Consanguinity is a social custom unrelated to ethnicity and religion and has persisted for thousands of years in some parts of the world (1,3). Recently, studies have suggested that consanguinity alters the gene frequencies in offspring of consanguineous parents and thus changes the risk of lymphoid malignancies in children and possibly other tumors (4,5). On the other side, there is no evidence that consanguinity, through genetics, affects development of cervical cancer. This is in agreement with established causal role of human papillomavirus (HPV) infection which is found in almost all instances of cervical carcinomas (6). Therefore, hypothesis presented below is dealing with consanguinity as an environmental risk factor for cervical carcinoma.
SETTING THE STAGE Factors that contribute to human papillomavirus infection and development of cervical cancer Evidence of infection with HPV is found in 90 percent of women with cervical carcinoma. The DNA of high-risk
321
322 Denic
types of virus, HPV16, 18, 31, 33, and 45, are found integrated in DNA and immortalize the cells of cervical epithelium. The low-risk types of virus are associated with benign genital warts and their DNA is not integrated in the host DNA (6). The behavior of men and women conducive to acquisition of HPV infection – risk factors for cervical carcinoma – are sexual intercourse at early age, multiple sex partners, sex partners who themselves had multiple partners. Because not all infected women develop cervical cancer, other factors like smoking, use of contraceptive pills, pregnancies, and immune deficiency, are important to promote transition of immortalize cell into irreversible phase of carcinogenesis (7). Types of consanguineous marriages Geneticists classify consanguineous marriages according to the coefficient of inbreeding. The coefficient of inbreeding is a probability that an offspring of consanguineous couple will have the same two alleles (homozygosity) by descent (8). This classification is based on how close genetically are married relatives. Thus, in order of decreasing inbreeding rate, the following six types of marriages are most common: uncleniece and double first-cousin, first-cousin, first-cousin once removed, second-cousin, and second-cousin once removed (Fig. 1). The first-cousin marriages are most common type worldwide.
However, if a criterion of marriage classification is whether the spouses belong to the same generation or not, than there are two groups of marriages. In the first group, spouses belong to the same generation (double first-cousin, first-cousin, and second-cousin). In the second group, spouses belong to different generations (uncle-niece, first-cousin once removed, and secondcousin once removed) (Fig. 1). Overall, in consanguineous populations, marriages in which spouses belong to the same generation are more common. Biological imprinting of Westermarck In 1891, Edward Westermarck proposed that avoidance of incest, i.e., sexual relationship between brother and sister and (grand) parents and children, comes from a long lasting inhibitions that develops during the time spent together with children in earliest period of life. Westermarck put forward this theory after several years of observational filed studies in Morocco where, among other things, he studied consanguineous marriages (9). Sex avoidance between brothers and sisters is universal across the cultures, and different hypotheses were proposed to explain incest taboo. Today, Westermarck’s theory has gained most acceptances because of a strong evidentiary support. In animals, studies have shown that sex avoidance between siblings is widespread. This is explained by biological imprinting that occurs early in life. Thus, if
Fig. 1 Types of consanguineous marriages. In the upper row, married relatives belong to the same generation and are likely to spend more time together during childhood than married relatives who are one generation removed (lower row).
Medical Hypotheses (2003) 60(3), 321–324
ª 2003 Elsevier Science Ltd. All rights reserved.
Consanguinity as risk factor for cervical carcinoma
brother and sister are reared separately, they will mate as adults because they have no way of knowing that they are related. If they are reared together, they will avoid mutual sex because they are biologically imprinted to feel sexual aversion to each other. Therefore, sex avoidance between related animals is not genetically determined but is an epigenetic phenomenon, and supports biological imprinting as a mechanism of incest avoidance (10). The existence of Westermarck’s effect in human-animal further supports the results from human studies. In one such study, in Israeli kibbutzim, boys and girls were put in groups and risen together from the earliest age in situation resembling that in which brothers and sisters are typically reared together. When they married later in life, it was found that they never married a peer from their group despite having an opportunity to do so. For example, among 2769 marriages, not a single couple was found to have been from the same peer group (11). In China, an unusual social custom at one time served as a natural experiment for testing validity of Westermarck’s theory. Some mothers gave up their daughters after birth and adopted daughters of other women. They reared adopted daughters as real daughters at their home in order to marry them to their sons. After growing together as brother and sister, a brother married his nongenetic sister, and entered in a so-called sim-pua union. The sim-pua marriages, when compared with marriages in which spouses did not know themselves in childhood, where characterized by the higher divorce rate, lower fertility rate, and higher rate of visiting brothels by men (12). This suggests existence of sexual aversion between partners who grow up together in early childhood and than were forced to marry. Further, when divorcee of sim-pua marriages remarried, the previously increased rates of divorce, infertility and brothel frequenting by men disappeared, further giving credence to theory of sexual aversion by imprinting. That familiarity breeds contempt for sex also support the results of a study of consanguineous marriages in Lebanon. In this study, higher divorce and lower fertility rates were found in parallel-cousin marriages (13). In parallel-cousin marriages, man marries his father’s brother daughter or his mother’s sister daughter. In some consanguineous societies, e.g., Bhutanese and Amazonian Indians, parallel cousins are treated as one’s own brother and sister and are not allowed to marry (14).
323
separate older boys and girls. In traditional societies where consanguineous marriages are more common, cousins are likely to spend more time together than in industrialized nations. While many of the relatives are brought together as ‘brothers and sisters,’ the opposite sex cousins become sexually negatively imprinted. This is identical phenomenon to the imprinting that takes place in genetic brothers and sisters, which creates incest taboo, i.e., sex avoidance between the members of nuclear family. The strength of Westermarck’s effect depends on two main parameters: first, on the age of children – until three being the most sensitive period – and, second, on the length of time relatives spend together. Consequently, in the consanguineous spouses who belong to the same generation (double-first, first-, and second-cousin marriages), negative imprinting is likely to be stronger than in the spouses who are one generation removed (first-cousin once removed, secondcousin once removed and uncle-niece marriages) (Fig. 1). Similarly, in the consanguineous spouses who are genetically closer, negative imprinting is likely to be stronger as they parents are both geographically and emotionally closer, hence a higher likelihood of spending more time together. Later is supported with the observations that parallel-cousin marriages may be less fertile, has higher divorce rate, and are banned in some consanguineous societies that otherwise permit crosscousin marriages which have the same coefficient of inbreeding (13,14). Development of sexual aversion to a relative leads to sex avoidance, but has no effect on overall sexual desire. Therefore, the spouses from consanguineous marriages are more likely to look for libidinal satisfaction outside marriage than those from non-consanguineous marriages. Thus, a wife in consanguineous marriage is at increased risk of acquiring HPV infection from another man or from her husband infected by different woman. Westermarck’s effect is over 99% efficacious in suppressing sex between brothers and sisters. In consanguineous couples, Westermarck’s effect produces weaker sexual inhibition that causes mild sexual antipathy between relatives. In most couples, it does not affect fertility rate, parallel-cousin marriages being the only documented exception. In other words, consanguineous marriages are forme frustae of sim-pua marriages. HYPOTHESIS STATED
THE PLAY Children from the same extended family are likely to know each other from the earliest days of their life. The opposite sex cousins play and often intimately live together, even in those societies that later customarily ª 2003 Elsevier Science Ltd. All rights reserved.
Consanguineous couples have mild mutual aversion to sex because they have been negatively imprinted during childhood. Their underlying sexual desire is unaffected and, to satisfy libido, some of them will seek sex outside marriage. This behavior is an established risk factor for Medical Hypotheses (2003) 60(3), 321–324
324 Denic
HPV infection. Consequently, a woman who marries a relative is at increased risk of being infected with HPV and developing cervical carcinoma. The risk is directly related to the genetic and generational proximity of the spouses. EXTENSION OF HYPOTHESIS The risk factors for infection with the high-risk and lowrisk types of HPV are the same (6,7). Therefore, the spouses in consanguineous marriages, when compared to those in non-consanguineous marriages, are more likely to be seropositive for HPV and to have genital warts.
2. 3.
4.
5.
6.
7.
TESTING OF HYPOTHESIS A case-controlled study in consanguineous communities is best suited for investigation of consanguinity as a risk factor for cervical carcinoma. The frequency and type of consanguineous marriages among cervical carcinoma cases could be compared with the same in controls matched for age, marriage status and other risk factors for cervical carcinoma. Alternatively, a cohort of women from a consanguineous population could be interviewed about marriage status, consanguinity and other parameters that effect risk of HPV infection, and tested for presence of HPV antibody. REFERENCES 1. Alwan A., Modell B. Hereditary disorders in the Eastern Mediterranean Region: role of customary consanguineous
Medical Hypotheses (2003) 60(3), 321–324
8.
9. 10. 11.
12. 13.
14.
marriage. In: Community Control of Genetic and Congenital Disorders. EMRO Technical Publication Series; vol. 24. Alexandria, Egypt: WHO, 1997. ICC-Global prevalence of consanguinity http:// www.consang.net/Global_Prevalence/index.htm. Khlat M. Endogamy in the Arab world. In: A. S. Teebi, T. I. Farag (eds). Genetic Disorders Among Arab Populations. New York: Oxford University Press, 1997. Abdulrazzaq Y. M., Bener A., Al-Gazali L. I., Al-Khayat A. I., Micallef R., Gaber T. A study of possible deleterious effects of consanguinity. Clin Genet 1997; 51: 167–173. Bener A., Denic S., Al-Mazrouei M. Consanguinity and family history of cancer in children with leukemia and lymphomas. Cancer 2001; 92: 1–6. Benchimol S., Minden D. M. Viruses, oncogenes, and tumor suppressor genes. In: F. J. Tannock, R. P. Hill (eds). The Basic Science of Oncology, 3rd Edn. New York: McGraw-Hill, 1998. Anonymous, Oncology: Medical knowledge self-assessment program. Philadelphia: American College of Physicians – American Society of Internal Medicine, 1999. Sofaer J. A. Population genetics (Hardy–Weinberg equilibrium and factors affecting it). In: A. E. H. Emery, D. L. Rimoin (eds). Principles and Practice of Medical Genetics. New York: Churchill Livingstone, 1990. Westermarck E. The History of Human Marriage. London: Macmillan, 1894. Library of excerpts. Female sexual selection: part 2. http:// www.neoteny.org/a/ sexualselection.html. Shepher J. Mate selection among second generation kibbutz adolescents and adults: incest avoidance and negative imprinting. Arch Sexual Behav 1971; 1: 293–307. Wolf A. P. Westermarck Redivivus. Ann Rev Anthropol 1993; 22: 157–175. McCabe J. FBD marriage: further support for the Westermarck hypothesis of the incest taboo? Am Anthropol 1983; 85: 50–69. Bhutan: Serga mathang and serga khothkin in Eastern Bhutan. http://www.mypage.bluewin.ch/raonline/pages/ story/bt/btstmarriage01.html.
ª 2003 Elsevier Science Ltd. All rights reserved.
Consanguinity as risk factor for cervical carcinoma S. Denic UAE University, Al Ain, United Arab Emirates
Summary Cervical carcinoma is caused by human papillomavirus (HPV). Among the risk factors for HPV infection are having multiple sex partners and sex partners who themselves had multiple sex partners. Women married to relatives are more likely to become infected with HPV and develop cervical carcinoma. Consanguineous spouses have a mild sexual aversion to each other that leads to sex avoidance and increases likelihood of satisfying sexual desire outside the marriage. Sexual aversion develops as a result of spouses growing together in early childhood, which triggers biological imprinting of Westermarck. Westermarck’s effect prevents incest in nuclear family. In consanguineous family, it extends to spouses, producing mild sexual antipathy. Because of high prevalence of consanguinity worldwide, it is important to test this hypothesis. ª 2003 Elsevier Science Ltd. All rights reserved.
INTRODUCTION Marriages between relatives are common worldwide and lead to human inbreeding. Their health consequences are primarily linked to the increased risk of congenital malformations and autosomal recessive diseases (1). In addition to genetic pressure, a consanguineous marriage, as a way of life, imposes an environmental pressure upon the family. Because development of malignant neoplasms is related to genetic and environmental factors, a possible causal relationship between consanguinity and cancer should be examined, especially since cancer is generally not linked with consanguinity. Whether consanguinity alters the risk of cancer is important to know because hundreds of millions of individuals live in consanguineous families. The prevalence of consanguineous marriages, out of all marriages, is less than 1% in the West, 1% in South America, 4% in
Received 3 April 2002 Accepted 12 July 2002 Correspondence to: S. Denic MD, Department of Medicine, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates. Phone: +971-3-7039-677; Fax: +971-3-7672-995; E-mail: [email protected]
Japan and 10–50% in the North Africa, Middle East, south-west and south Asia. In populous Indochina and China the frequency of consanguineous marriages varies, rising above 50% in some segments of their populations (2). Consanguinity is a social custom unrelated to ethnicity and religion and has persisted for thousands of years in some parts of the world (1,3). Recently, studies have suggested that consanguinity alters the gene frequencies in offspring of consanguineous parents and thus changes the risk of lymphoid malignancies in children and possibly other tumors (4,5). On the other side, there is no evidence that consanguinity, through genetics, affects development of cervical cancer. This is in agreement with established causal role of human papillomavirus (HPV) infection which is found in almost all instances of cervical carcinomas (6). Therefore, hypothesis presented below is dealing with consanguinity as an environmental risk factor for cervical carcinoma.
SETTING THE STAGE Factors that contribute to human papillomavirus infection and development of cervical cancer Evidence of infection with HPV is found in 90 percent of women with cervical carcinoma. The DNA of high-risk
321
322 Denic
types of virus, HPV16, 18, 31, 33, and 45, are found integrated in DNA and immortalize the cells of cervical epithelium. The low-risk types of virus are associated with benign genital warts and their DNA is not integrated in the host DNA (6). The behavior of men and women conducive to acquisition of HPV infection – risk factors for cervical carcinoma – are sexual intercourse at early age, multiple sex partners, sex partners who themselves had multiple partners. Because not all infected women develop cervical cancer, other factors like smoking, use of contraceptive pills, pregnancies, and immune deficiency, are important to promote transition of immortalize cell into irreversible phase of carcinogenesis (7). Types of consanguineous marriages Geneticists classify consanguineous marriages according to the coefficient of inbreeding. The coefficient of inbreeding is a probability that an offspring of consanguineous couple will have the same two alleles (homozygosity) by descent (8). This classification is based on how close genetically are married relatives. Thus, in order of decreasing inbreeding rate, the following six types of marriages are most common: uncleniece and double first-cousin, first-cousin, first-cousin once removed, second-cousin, and second-cousin once removed (Fig. 1). The first-cousin marriages are most common type worldwide.
However, if a criterion of marriage classification is whether the spouses belong to the same generation or not, than there are two groups of marriages. In the first group, spouses belong to the same generation (double first-cousin, first-cousin, and second-cousin). In the second group, spouses belong to different generations (uncle-niece, first-cousin once removed, and secondcousin once removed) (Fig. 1). Overall, in consanguineous populations, marriages in which spouses belong to the same generation are more common. Biological imprinting of Westermarck In 1891, Edward Westermarck proposed that avoidance of incest, i.e., sexual relationship between brother and sister and (grand) parents and children, comes from a long lasting inhibitions that develops during the time spent together with children in earliest period of life. Westermarck put forward this theory after several years of observational filed studies in Morocco where, among other things, he studied consanguineous marriages (9). Sex avoidance between brothers and sisters is universal across the cultures, and different hypotheses were proposed to explain incest taboo. Today, Westermarck’s theory has gained most acceptances because of a strong evidentiary support. In animals, studies have shown that sex avoidance between siblings is widespread. This is explained by biological imprinting that occurs early in life. Thus, if
Fig. 1 Types of consanguineous marriages. In the upper row, married relatives belong to the same generation and are likely to spend more time together during childhood than married relatives who are one generation removed (lower row).
Medical Hypotheses (2003) 60(3), 321–324
ª 2003 Elsevier Science Ltd. All rights reserved.
Consanguinity as risk factor for cervical carcinoma
brother and sister are reared separately, they will mate as adults because they have no way of knowing that they are related. If they are reared together, they will avoid mutual sex because they are biologically imprinted to feel sexual aversion to each other. Therefore, sex avoidance between related animals is not genetically determined but is an epigenetic phenomenon, and supports biological imprinting as a mechanism of incest avoidance (10). The existence of Westermarck’s effect in human-animal further supports the results from human studies. In one such study, in Israeli kibbutzim, boys and girls were put in groups and risen together from the earliest age in situation resembling that in which brothers and sisters are typically reared together. When they married later in life, it was found that they never married a peer from their group despite having an opportunity to do so. For example, among 2769 marriages, not a single couple was found to have been from the same peer group (11). In China, an unusual social custom at one time served as a natural experiment for testing validity of Westermarck’s theory. Some mothers gave up their daughters after birth and adopted daughters of other women. They reared adopted daughters as real daughters at their home in order to marry them to their sons. After growing together as brother and sister, a brother married his nongenetic sister, and entered in a so-called sim-pua union. The sim-pua marriages, when compared with marriages in which spouses did not know themselves in childhood, where characterized by the higher divorce rate, lower fertility rate, and higher rate of visiting brothels by men (12). This suggests existence of sexual aversion between partners who grow up together in early childhood and than were forced to marry. Further, when divorcee of sim-pua marriages remarried, the previously increased rates of divorce, infertility and brothel frequenting by men disappeared, further giving credence to theory of sexual aversion by imprinting. That familiarity breeds contempt for sex also support the results of a study of consanguineous marriages in Lebanon. In this study, higher divorce and lower fertility rates were found in parallel-cousin marriages (13). In parallel-cousin marriages, man marries his father’s brother daughter or his mother’s sister daughter. In some consanguineous societies, e.g., Bhutanese and Amazonian Indians, parallel cousins are treated as one’s own brother and sister and are not allowed to marry (14).
323
separate older boys and girls. In traditional societies where consanguineous marriages are more common, cousins are likely to spend more time together than in industrialized nations. While many of the relatives are brought together as ‘brothers and sisters,’ the opposite sex cousins become sexually negatively imprinted. This is identical phenomenon to the imprinting that takes place in genetic brothers and sisters, which creates incest taboo, i.e., sex avoidance between the members of nuclear family. The strength of Westermarck’s effect depends on two main parameters: first, on the age of children – until three being the most sensitive period – and, second, on the length of time relatives spend together. Consequently, in the consanguineous spouses who belong to the same generation (double-first, first-, and second-cousin marriages), negative imprinting is likely to be stronger than in the spouses who are one generation removed (first-cousin once removed, secondcousin once removed and uncle-niece marriages) (Fig. 1). Similarly, in the consanguineous spouses who are genetically closer, negative imprinting is likely to be stronger as they parents are both geographically and emotionally closer, hence a higher likelihood of spending more time together. Later is supported with the observations that parallel-cousin marriages may be less fertile, has higher divorce rate, and are banned in some consanguineous societies that otherwise permit crosscousin marriages which have the same coefficient of inbreeding (13,14). Development of sexual aversion to a relative leads to sex avoidance, but has no effect on overall sexual desire. Therefore, the spouses from consanguineous marriages are more likely to look for libidinal satisfaction outside marriage than those from non-consanguineous marriages. Thus, a wife in consanguineous marriage is at increased risk of acquiring HPV infection from another man or from her husband infected by different woman. Westermarck’s effect is over 99% efficacious in suppressing sex between brothers and sisters. In consanguineous couples, Westermarck’s effect produces weaker sexual inhibition that causes mild sexual antipathy between relatives. In most couples, it does not affect fertility rate, parallel-cousin marriages being the only documented exception. In other words, consanguineous marriages are forme frustae of sim-pua marriages. HYPOTHESIS STATED
THE PLAY Children from the same extended family are likely to know each other from the earliest days of their life. The opposite sex cousins play and often intimately live together, even in those societies that later customarily ª 2003 Elsevier Science Ltd. All rights reserved.
Consanguineous couples have mild mutual aversion to sex because they have been negatively imprinted during childhood. Their underlying sexual desire is unaffected and, to satisfy libido, some of them will seek sex outside marriage. This behavior is an established risk factor for Medical Hypotheses (2003) 60(3), 321–324
324 Denic
HPV infection. Consequently, a woman who marries a relative is at increased risk of being infected with HPV and developing cervical carcinoma. The risk is directly related to the genetic and generational proximity of the spouses. EXTENSION OF HYPOTHESIS The risk factors for infection with the high-risk and lowrisk types of HPV are the same (6,7). Therefore, the spouses in consanguineous marriages, when compared to those in non-consanguineous marriages, are more likely to be seropositive for HPV and to have genital warts.
2. 3.
4.
5.
6.
7.
TESTING OF HYPOTHESIS A case-controlled study in consanguineous communities is best suited for investigation of consanguinity as a risk factor for cervical carcinoma. The frequency and type of consanguineous marriages among cervical carcinoma cases could be compared with the same in controls matched for age, marriage status and other risk factors for cervical carcinoma. Alternatively, a cohort of women from a consanguineous population could be interviewed about marriage status, consanguinity and other parameters that effect risk of HPV infection, and tested for presence of HPV antibody. REFERENCES 1. Alwan A., Modell B. Hereditary disorders in the Eastern Mediterranean Region: role of customary consanguineous
Medical Hypotheses (2003) 60(3), 321–324
8.
9. 10. 11.
12. 13.
14.
marriage. In: Community Control of Genetic and Congenital Disorders. EMRO Technical Publication Series; vol. 24. Alexandria, Egypt: WHO, 1997. ICC-Global prevalence of consanguinity http:// www.consang.net/Global_Prevalence/index.htm. Khlat M. Endogamy in the Arab world. In: A. S. Teebi, T. I. Farag (eds). Genetic Disorders Among Arab Populations. New York: Oxford University Press, 1997. Abdulrazzaq Y. M., Bener A., Al-Gazali L. I., Al-Khayat A. I., Micallef R., Gaber T. A study of possible deleterious effects of consanguinity. Clin Genet 1997; 51: 167–173. Bener A., Denic S., Al-Mazrouei M. Consanguinity and family history of cancer in children with leukemia and lymphomas. Cancer 2001; 92: 1–6. Benchimol S., Minden D. M. Viruses, oncogenes, and tumor suppressor genes. In: F. J. Tannock, R. P. Hill (eds). The Basic Science of Oncology, 3rd Edn. New York: McGraw-Hill, 1998. Anonymous, Oncology: Medical knowledge self-assessment program. Philadelphia: American College of Physicians – American Society of Internal Medicine, 1999. Sofaer J. A. Population genetics (Hardy–Weinberg equilibrium and factors affecting it). In: A. E. H. Emery, D. L. Rimoin (eds). Principles and Practice of Medical Genetics. New York: Churchill Livingstone, 1990. Westermarck E. The History of Human Marriage. London: Macmillan, 1894. Library of excerpts. Female sexual selection: part 2. http:// www.neoteny.org/a/ sexualselection.html. Shepher J. Mate selection among second generation kibbutz adolescents and adults: incest avoidance and negative imprinting. Arch Sexual Behav 1971; 1: 293–307. Wolf A. P. Westermarck Redivivus. Ann Rev Anthropol 1993; 22: 157–175. McCabe J. FBD marriage: further support for the Westermarck hypothesis of the incest taboo? Am Anthropol 1983; 85: 50–69. Bhutan: Serga mathang and serga khothkin in Eastern Bhutan. http://www.mypage.bluewin.ch/raonline/pages/ story/bt/btstmarriage01.html.
ª 2003 Elsevier Science Ltd. All rights reserved.