Age-standardized Incidence Rates for Leukemia Associated with Consanguineous Marriages in 68 Countries, an Ecological Study
Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran
Received: December 30, 2014
Accepted: March 30, 2015
Mediterr J Hematol Infect Dis 2015, 7(1): e2015027, DOI 10.4084/MJHID.2015.027
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Consanguineous marriage that defines as a union between biologically related persons has a variety of known deleterious correlations with factors that affect public health within human populations. To investigate the association between the mean of inbreeding coefficient(α) and incidence of leukemia, the present ecological study on 68 countries was carried out. Statistical analysis showed that the age-standardized incidence rate of leukemia positively correlated with log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with log10α (r=-0.609, df=66, P<0.001). Controlling log10GNI per capita, a significant negative correlation between log10 and the age-standardized incidence rate of leukemia was observed (r=-0.392, df=65, P=0.001). The countries were stratified according to their annual GNI per capita, low and high-income countries with GNI per capita less than and more than 10,000$, respectively. Statistical analysis showed that in high-income countries, after controlling for log10GNI per capita, the correlation between the age-standardized incidence rate of leukemia and log10α was still significant (r=-0.600, df=36, P<0.001). It should be noted that there was no significant association between the age-standardized mortality rate due to leukemia and log10α (P>0.05). The present finding indicates that the rate of leukemia, age-standardized for incidence, is lower in countries with a high prevalence of consanguineous marriages.
Consanguineous marriage defined as a union between biologically
related persons has a long-standing social habit among some
populations. Its prevalence depends on many factors, such as
demographic, religious, cultural and socio-economic factors.[1-4]
Consanguinity has a variety of known deleterious correlations with factors that affect public health within human populations.[1,5-14] However, there were some reports that described a negative association between consanguinity and risk of diseases.[15-17] A negative association was reported between the susceptibility to infection with HIV-1 and inbreeding coefficient. Based on an ecologic study the mean of inbreeding coefficient (at the population level; α) is negatively associated with age-standardized mortality rate due to breast cancer. This means that the countries with a high level of consanguinity show a low level of age-standardized mortality rates due to breast cancer. A significant relationship between parental consanguinity and clinical response to chemotherapy among locally advanced breast cancer patients has been reported.
It is well established that genetic components involved in the risk of several types of cancers, including leukemia.[18-24] On the other hand, consanguinity increases the homozygosity of the offspring. Therefore, for countries such as our country, where the consanguineous marriage is common, the association between consanguinity and incidence of leukemia or mortality due to leukemia is highly important for public health programs. Therefore, the present ecological study was carried out.
Materials and methods
The age-standardized rate is the number of new cases or deaths per
100,000 persons per year. An age-standardized rate is the rate that a
population would have if it had a standard age structure.
Standardization is necessary when comparing several populations that
differ with respect to age because age has a powerful influence on the
risk of cancer. Data about age-standardized incidence rates and
age-standardized mortality rates for leukemia (per 100,000 persons per
year) were obtained from the WHO website. The inbreeding
coefficient is the probability that an individual has received both
alleles of a pair from an identical ancestral. The mean of inbreeding
coefficient (α) values for the countries were obtained from the
website. In the present study, we used gross national income per
capita (GNI, annual; at international dollars) as a confounding factor.
Data about GNI per capita for 2012 were obtained from the WHO
website. Inclusion criteria for selection of countries were based
on the availability of the variables mentioned above (Table 1).
Statistical analysis. Kolmogorov-Smirnov test indicates that the GNI per capita and α have an abnormal distribution (For GNI per capita: Kolmogorov-Smirnov Z-test=1.276, P=0.077; For α Kolmogorov-Smirnov Z-test=2.043, P<0.001). Logarithmic transformation (log10) was used on GNI per capita (named log10GNI) and α (named log10α) because they had skewed distributions, and the logarithmic transformations brought them closer to a normal distribution. Correlations between the variables having normal distribution or the logarithmic transformation of the variables not showing normal distribution were determined using the parametric Pearson's correlation coefficient analysis. Multiple regression analysis was carried out. Also, the partial correlation coefficient analysis was carried out. Statistical analysis was performed using SPSS (version 11.5) statistical software package. A probability of P<0.05 was considered statistically significant. All statistical tests were two-sided.
Table 1 represents the mean
of inbreeding coefficients, GNI per capita; age-standardized incidence
rate and age-standardized mortality rate in the study countries.
There was no significant association between the age-standardized mortality rate due to leukemia and log10α before and/or after controlling for the log10GNI per capita (Table 2). However, it is not the same as a previous report that indicates that the age-standardized mortality rate due to breast cancer is negatively correlated with the mean of inbreeding coefficient (α).
Statistical analysis showed that the age-standardized incidence of leukemia positively correlated with the log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with the log10α (r=-0.609, df=66, P<0.001). In multiple regression analysis, age-standardized incidence or age-standardized mortality from leukemia were used as dependent variables and log10GNI and log10α were used as independent variables. It should be noted that logand log10αGNI per capita had a significant correlation with each other (r=-0.531, df=66, P<0.001). However, the multiple regression analysis showed that there was no significant collinearity. Partial correlation analysis was carried out in order to eliminate the effect of possible confounding effect of GNI per capita on the association between the age-standardized incidence rate of leukemia and log10α. After checking the log10GNI pern capita, the log10α showed a significant negative correlation with the age-standardized incidence of leukemia (r=-0.392, df=65, P=0.001).
We noted a possible lack of reliable data from low-income countries. Therefore, we stratified the countries according to their GNI per capita, low and high-income countries with GNI per capita less than and more than 10,000$, respectively. Statistical analysis showed that in high-income countries, after controlling the log10GNI per capita, the correlation between the age-standardized incidence rate of leukemia and log10α was significant (r=-0.600, df=36, P<0.001).
|Table 1. Mean of inbreeding coefficients, GNI per capita, age-standardized incidence rate and age-standardized mortality rate in the study countries.|
|Table 2. Correlation coefficients between age-standardized rates (ASR) for incidence of leukemia and mortality due to leukemia and study variables.|
The main finding of the present study is the negative association
between age-standardized incidence rate for leukemia and mean of
inbreeding coefficient (α). This means that countries are having a high
frequency of consanguinity, show a low level of age-standardized
incidence rates for leukemia. This finding is not easy to interpret.
A significant positive association between level of inbreeding coefficient (due to consanguineous marriages) and risk of cancers (including leukemia) has been reported by some studies.[29-32] However, several studies had shown that countries with high consanguinity demonstrate lower age-standardized mortality rates and incidence in breast cancer.[15,33,34]
It is well established that the prevalence of consanguinity is mostly present in some regions.[1,25,27,35,36] The prevalence of consanguineous marriages is remarkably higher in many Asian and African countries compared with the Western countries. On the hand, the data published by WHO, show the estimated age-standardized incidence of leukemia in the Asian (3.9 per 100,000 persons per year) and African (3.0 per 100,000 persons per year) countries was significantly lower than in North America (8.7 per 100,000 persons per year) and European countries (7.0 per 100,000 persons per year).
At present, it is very difficult to establish how much the consanguinity, high in Eastern countries, contributes to this difference or if this reflects only ethnic and environmental factors.
We know that there are several types of leukemia and genetic elements involved in the pathogenesis of each type might be differing from the other types.[18-24] However, for estimating the age-standardized incidence and mortality rates, all of leukemia types were pooled.
The present study is an ecological study. Other studies (such as case-control and cohort studies) are necessary for concluding that a large proportion of death could attribute to inbreeding due, in several countries, to the high prevalence of consanguinity.
- Bittles AH. Consanguinity and its relevance to clinical genetics. Clin Genet 2001;60: 89-98. http://dx.doi.org/10.1034/j.1399-0004.2001.600201.x PMid:11553039 .
- Akrami SM, Osati Z. Is consanguineous marriage religiously encouraged? Islamic and Iranian considerations. J Biosoc Sci 2007;39:313-6. http://dx.doi.org/10.1017/S0021932006001684 PMid:17059617 .
- Saadat M. Consanguineous marriages in Iranian folktales. Community Genet 2007;10: 38-40. http://dx.doi.org/10.1159/000096280 PMid:17167249 .
- Saadat M. Is consanguineous marriage historically encouraged? J Biosoc Sci 2008;40: 153-4. http://dx.doi.org/10.1017/S0021932007002416 PMid:18303588 .
- Kelmemi W, Chelly I, Kharrat M, Chaabouni-Bouhamed H. Consanguinity and homozygosity among Tunisian patients with an autosomal recessive disorder. J Biosoc Sci 2015;29:1-9. http://dx.doi.org/10.1017/S002193201400056X PMid:25630711 .
- Saadat M, Zendeh-Bodi Z. Correlation between incidences of self-inflicted burns and means of inbreeding coefficients, an ecologic study. Ann Epidemiol 2006;16:708-11. http://dx.doi.org/10.1016/j.annepidem.2005.12.006 PMid:16549366 .
- Saadat M. Consanguinity and national IQ scores. J Epidemiol Community Health 2008;62:566-7. http://dx.doi.org/10.1136/jech.2007.069021 PMid:18477759 .
- Chaman R, Gholami Taramsari M, Khosravi A, Amiri M, Holakouie Naieni K, Yunesian M. Consanguinity and neonatal death: a nested case-control study. J Family Reprod Health. 2014;8:189-93. PMid:25530772 PMCid:PMC4266791 .
- Nafissi S, Ansari-Lari M, Saadat M. Effect of inbreeding on weight gain of offspring from birth to 12 months after birth: a study from Iran. J Biosoc Sci 2010;42:195-200. http://dx.doi.org/10.1017/S0021932009990393 PMid:19852867 .
- Saadat M, Vakili-Ghartavol R. Parental consanguinity and susceptibility to drug abuse among offspring, a case-control study. Psychiatry Res 2010;180:57-9. http://dx.doi.org/10.1016/j.psychres.2010.04.040 PMid:20488549 .
- Anvar Z, Namavar-Jahromi B, Saadat M. Association between consanguineous marriages and risk of pre-eclampsia. Arch Gynecol Obstet 2011;283 Suppl 1:5-7. http://dx.doi.org/10.1007/s00404-010-1528-8 PMid:20517614 .
- Nafissi S, Ansari-Lari M, Saadat M. Parental consanguineous marriages and age at onset of schizophrenia. Schizophr Res 2011;126:298-9. http://dx.doi.org/10.1016/j.schres.2010.11.029 PMid:21185696 .
- Saadat M. Association between healthy life expectancy at birth and consanguineous marriages in 63 countries. J Biosoc Sci 2011;43:475-80. http://dx.doi.org/10.1017/S0021932011000034 PMid:21306664 .
- Saadat M. Influence of parental consanguineous marriages on age at onset of bipolar disorder. Psychiatry Res 2012;198:327-8. http://dx.doi.org/10.1016/j.psychres.2012.01.013 PMid:22417937 .
- Saadat M, Saadat I. Correlation between consanguineous marriages and age-standardized mortality rate due to breast cancer, an ecologic study. Breast Cancer Res Treat 2010;121:795-7. http://dx.doi.org/10.1007/s10549-009-0711-8 PMid:20052537 .
- Saadat M, Khalili M, Omidvari S, Ansari-Lari M. Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients. Cancer Lett 2011;302:109-12. http://dx.doi.org/10.1016/j.canlet.2010.12.017 PMid:21227572 .
- Rajaei M, Saadat M. Association between inbreeding coefficient and susceptibility to HIV-1 infection, a case-control study. Germs 2013;3:122-5. http://dx.doi.org/10.11599/germs.2013.1046 PMid:24432296 PMCid:PMC3882852 .
- Enciso-Mora V, Hosking FJ, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JA, Tomlinson IP, Allan JM, Taylor M, Greaves M, Houlston RS. Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia. Leukemia 2012;26:2212-5. http://dx.doi.org/10.1038/leu.2012.89 PMid:22456626 .
- Lan Q, Au WY, Chanock S, Tse J, Wong KF, Shen M, Siu LP, Yuenger J, Yeager M, Hosgood HD 3rd, Purdue MP, Liang R, Rothman N. Genetic susceptibility for chronic lymphocytic leukemia among Chinese in Hong Kong. Eur J Haematol 2010; 85:492-5. http://dx.doi.org/10.1111/j.1600-0609.2010.01518.x PMid:20731705 PMCid:PMC2980583 .
- Crowther-Swanepoel D, Qureshi M, Dyer MJ, Matutes E, Dearden C, Catovsky D, Houlston RS. Genetic variation in CXCR4 and risk of chronic lymphocytic leukemia. Blood 2009;114:4843-6. http://dx.doi.org/10.1182/blood-2009-07-235184 PMid:19812382 .
- Ng D, Toure O, Wei MH, Arthur DC, Abbasi F, Fontaine L, Marti GE, Fraumeni JF Jr, Goldin LR, Caporaso N, Toro JR. Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia. Blood 2007;109:916-25. http://dx.doi.org/10.1182/blood-2006-03-011825 PMid:17047154 .
- Ng D, Marti GE, Fontaine L, Toro JR, Caporaso N, Goldin LR. High-density mapping and follow-up studies on chromosomal regions 1, 3, 6, 12, 13 and 17 in 28 families with chronic lymphocytic leukaemia. Br J Haematol 2006;133:59-61. http://dx.doi.org/10.1111/j.1365-2141.2006.05972.x .
- Sellick GS, Webb EL, Allinson R, Matutes E, Dyer MJ, Jonsson V, Langerak AW, Mauro FR, Fuller S, Wiley J, Lyttelton M, Callea V, Yuille M, Catovsky D, Houlston RS. A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci. Am J Hum Genet 2005;77:420-9. http://dx.doi.org/10.1086/444472 PMid:16080117 PMCid:PMC1226207 .
- Goldin LR, Ishibe N, Sgambati M, Marti GE, Fontaine L, Lee MP, Kelley JM, Scherpbier T, Buetow KH, Caporaso NE. A genome scan of 18 families with chronic lymphocytic leukaemia. Br J Haematol 2003;121:866-73. http://dx.doi.org/10.1046/j.1365-2141.2003.04372.x PMid:12786797 .
- Saadat M, Ansari-Lari M, Farhud DD. Consanguineous marriage in Iran. Ann Hum Biol 2004;31:263-9. http://dx.doi.org/10.1080/03014460310001652211 PMid:15204368 .
- Bener A, Moore MA, Ali R, El Ayoubi HR. Impacts of family history and lifestyle habits on colorectal cancer risk: a case-control study in Qatar. Asian Pac J Cancer Prev 2010;11:963-8. PMid:21133608 .
- Siraj AK, Khalak HG, Sultana M, Al-Rasheed M, Bavi P, Al-Sanea N, Al-Dayel F, Uddin S, Alkuraya FS, Al-Kuraya KS. Colorectal cancer risk is not associated with increased levels of homozygosity in Saudi Arabia. Genet Med 2012; doi: 10.1038/gim.2012.27 http://dx.doi.org/10.1038/gim.2012.27 .
- Feldman JG, Lee SL, Seligman B. Occurrence of acute leukemia in females in a genetically isolated population. Cancer 1976;38:2548-50. http://dx.doi.org/10.1002/1097-0142(197612)38:6<2548::AID-CNCR2820380644>3.0.CO;2-Y .
- Bener A, El Ayoubi HR, Chouchane L, Ali AI, Al-Kubaisi A, Al-Sulaiti H, Teebi AS. Impact of consanguinity on cancer in a highly endogamous population. Asian Pac J Cancer Prev 2009;10:35-40. PMid:19469621 .
- Bener A, Ayoubi HR, Ali AI, Al-Kubaisi A, Al-Sulaiti H. Does consanguinity lead to decreased incidence of breast cancer? Cancer Epidemiol 2010;34:413-8. http://dx.doi.org/10.1016/j.canep.2010.04.004 PMid:20451484 .
- Elalaoui SC, Jaouad IC, Laarabi FZ, Elgueddari Bel K. Low level of consanguinity in moroccan families at high risk of breast cancer. Asian Pac J Cancer Prev 2013;14: 723-6. http://dx.doi.org/10.7314/APJCP.2013.14.2.723 PMid:23621226 .
- El-Kheshen G, Saadat M. Prevalence of consanguineous marriages among Shi'a populations of Lebanon. J Biosoc Sci 2013;45:675-82. http://dx.doi.org/10.1017/S0021932012000843 PMid:23302154 .
- Saadat M, Tajbakhsh K. Prevalence of consanguineous marriages in west and south of Afghanistan. J Biosoc Sci 2013;45:799-805. http://dx.doi.org/10.1017/S0021932012000661 PMid:23151388 .