Gestational trophoblastic neoplasia risk factors
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]
Overview
Common risk factors in the development choriocarcinoma include extremes of parental reproductive age, history of gestational trophoblastic disease, reproductive factors such as parity and abortion, parental blood group, oral contraceptive use, genetic factors, and environmental and lifestyle factors.
Risk factors
Parental Age
Maternal
- The risk of choriocarcinoma increases progressively in women older than 25 years (relative risk 1·4).[1]
- The risk increases more rapidly in women older than 39 years (relative risk 10·8).[1]
- The risk is higher for women younger than 20 compared with women aged 20 – 24 years (relative risk 1·5).[1]
Paternal
- A case-control study by La Vecchia et al revealed increased risk of gestational trophoblastic disease in general in women with husbands older than 40 (RR= 1.6 [95% CI 0·9 – 6·0] for age 41 - 45 years and RR= 4.9 [95% CI 2·2 – 11·1] for age > 45 years).[2]
- Paternal age > 45 years can also independently be associated with an increased risk of complete hydatidiform mole (CHM), a potential prerequisite of choriocarcinoma (RR= 2.9).[3]
History of Gestational Trophoblastic Disease
- Previous history of hydatidiform mole is associated with a 1000 – 2000 times increased risk of choriocarcinoma.[1]
- The risk of choriocarcinoma after a complete hydatidiform mole (CHM) is about 2500 times higher than after a live birth.[1]
Reproductive Factors
- Studies on gestational trophoblastic disease in general have shown a relative risk of 0·6 - 1·0 for parous women compared with nulliparous women.[4][5][6]
- Parous women also have an increased risk of choriocarcinoma (RR above unity). But this association is significant only for more than five births (RR= 5.2).[7]
- Abortion is associated with an increased risk of gestational trophoblastic disease in general (RR= 1.1 - 3.3).[8][9][4][5][6]
- The risk of choriocarcinoma increases with parity. The relative risk based on parity is as follows:
- The risk of choriocarcinoma also increases with the history of abortion. Relative risk for 1 and 2 abortions is 1.2 (95% CI: 0·5–2·9) and 0.8 (95% CI: 0·3 – 2·5) respectively.[7]
- A study on choriocarcinoma from Vietnam has shown a relative risk of 0·3 for a history of induced abortions.[7]
Parental Blood Group
- Women of blood group A married to males of blood group O have the highest risk of chroiocarcinoma compared to women of blood group A married to males of blood group A (RR= 10.4).[10]
Oral Contraceptives
- The risk of choriocarcinoma increases with the use of oral contraceptives. Relative risk ranges from 2.0 to 6.4.[11][12][13]
- The use of oral contraceptives after a molar evacuation increases the risk of invasive mole and choriocarcinoma by approximately three times.[1]
Genetic Factors
Mutation in the following genes has been associated with recurrent hydatidiform mole:
- NLR family, pyrin domain-containing 7 (NLRP7)[14][15]
- KHDC3-like protein, subcortical maternal complex member (KHDC3L)[14][15]
Environmental and Lifestyle Factors
- There is limited information regarding the association of gestational trophoblastic disease in general and smoking, alcohol, diet, socioeconomic status, and herbicide exposure.
- Relative risk is > 2 for hydatidiform mole (HM) and choriocarcinoma in smoker women. The risk increases with longer duration (RR for ≥10 years 4·2; 95% CI 1·6 – 10·8).[11][6][7]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Buckley JD (March 1984). "The epidemiology of molar pregnancy and choriocarcinoma". Clin Obstet Gynecol. 27 (1): 153–9. PMID 6705308.
- ↑ La Vecchia C, Parazzini F, Decarli A, Franceschi S, Fasoli M, Favalli G, Negri E, Pampallona S (September 1984). "Age of parents and risk of gestational trophoblastic disease". J. Natl. Cancer Inst. 73 (3): 639–42. PMID 6088880.
- ↑ Parazzini, F.; Vecchia, C. La; Pampallona, S. (1986). "Parental age and risk of complete and partial hydatidiform mole". BJOG: An International Journal of Obstetrics and Gynaecology. 93 (4): 582–585. doi:10.1111/j.1471-0528.1986.tb07957.x. ISSN 1470-0328.
- ↑ 4.0 4.1 Brinton, Louise A.; Wu, Bao-Zhen; Wang, Wen; Ershow, Abby G.; Song, Hong-Zhao; Li, Jun-Yao; Bracken, Michael B.; Blot, William J. (1989). "Gestational trophoblastic disease: A case-control study from the People's Republic of China". American Journal of Obstetrics and Gynecology. 161 (1): 121–127. doi:10.1016/0002-9378(89)90248-2. ISSN 0002-9378.
- ↑ 5.0 5.1 Parazzini, Fabio; LaVecchia, Carlo; Pampallona, Sandro; Franceschi, Silvia (1985). "Reproductive patterns and the risk of gestational trophoblastic disease". American Journal of Obstetrics and Gynecology. 152 (7): 866–870. doi:10.1016/S0002-9378(85)80079-X. ISSN 0002-9378.
- ↑ 6.0 6.1 6.2 La Vecchia C, Franceschi S, Parazzini F, Fasoli M, Decarli A, Gallus G, Tognoni G (March 1985). "Risk factors for gestational trophoblastic disease in Italy". Am. J. Epidemiol. 121 (3): 457–64. PMID 2990199.
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Ha MC, Cordier S, Bard D, Le TB, Hoang AH, Hoang TQ, Le CD, Abenhaim L, Nguyen TN (1996). "Agent orange and the risk of gestational trophoblastic disease in Vietnam". Arch. Environ. Health. 51 (5): 368–74. doi:10.1080/00039896.1996.9934424. PMID 8896386.
- ↑ Talati NJ (October 1998). "The pattern of benign gestational trophoblastic disease in Karachi". J Pak Med Assoc. 48 (10): 296–300. PMID 10087749.
- ↑ Messerli, Marti L.; Lilienfeld, Abraham M.; Parmley, Tim; Woodruff, J. Donald; Rosenshein, Neil B. (1985). "Risk factors for gestational trophoblastic neoplasia". American Journal of Obstetrics and Gynecology. 153 (3): 294–300. doi:10.1016/S0002-9378(85)80115-0. ISSN 0002-9378.
- ↑ Bagshawe, K.D.; Rawlins, G.; Pike, M.C.; Lawler, SylviaD. (1971). "ABO BLOOD-GROUPS IN TROPHOBLASTIC NEOPLASIA". The Lancet. 297 (7699): 553–557. doi:10.1016/S0140-6736(71)91159-7. ISSN 0140-6736.
- ↑ 11.0 11.1 Baltazar JC (1976). "Epidemiological features of choriocarcinoma". Bull. World Health Organ. 54 (5): 523–32. PMC 2366480. PMID 1088402.
- ↑ Buckley JD, Henderson BE, Morrow CP, Hammond CB, Kohorn EI, Austin DF (February 1988). "Case-control study of gestational choriocarcinoma". Cancer Res. 48 (4): 1004–10. PMID 3338071.
- ↑ Palmer, J. R.; Driscoll, S. G.; Rosenberg, L.; Berkowitz, R. S.; Lurain, J. R.; Soper, J.; Twiggs, L. B.; Gershenson, D. M.; Kohorn, E. I.; Berman, M.; Shapiro, S.; Rao, R. S. (1999). "Oral Contraceptive Use and Risk of Gestational Trophoblastic Tumors". JNCI Journal of the National Cancer Institute. 91 (7): 635–640. doi:10.1093/jnci/91.7.635. ISSN 0027-8874.
- ↑ 14.0 14.1 Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R, Kuick R, Bagga R, Kircheisen R, Ao A, Ratti B, Hanash S, Rouleau GA, Slim R (March 2006). "Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans". Nat. Genet. 38 (3): 300–2. doi:10.1038/ng1740. PMID 16462743.
- ↑ 15.0 15.1 Parry DA, Logan CV, Hayward BE, Shires M, Landolsi H, Diggle C, Carr I, Rittore C, Touitou I, Philibert L, Fisher RA, Fallahian M, Huntriss JD, Picton HM, Malik S, Taylor GR, Johnson CA, Bonthron DT, Sheridan EG (September 2011). "Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte". Am. J. Hum. Genet. 89 (3): 451–8. doi:10.1016/j.ajhg.2011.08.002. PMC 3169823. PMID 21885028.