Ovarian cancer risk factors: Difference between revisions

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==Overview==
==Overview==
The risk of developing ovarian cancer appears to be affected by several factors; in fact, early age at first pregnancy, older ages of final pregnancy, and the use of low dose [[hormonal contraception]] have been associated with a lower incidence of ovarian cancer.  There is good evidence that in some women genetic factors are important.
The risk of developing [[ovarian cancer]] appears to be affected by several factors; in fact, early age at first [[pregnancy]], older ages of final [[pregnancy]], and the use of low dose [[hormonal contraception]] have been associated with a lower [[incidence]] of [[ovarian cancer]].  There is good evidence that in some women [[genetic]] factors are important.


==Risk Factors==
==Risk Factors==
The most important risk factor for ovarian cancer is a family history of a first-degree relative (e.g., mother, daughter, or sister) with the disease. Approximately 20% of ovarian cancers are familial, and although most of these are linked to mutations in the BRCA1 or BRCA2 genes, several other genes have been implicated in familial ovarian cancers.[6,7] The highest risk appears in women who have two or more first-degree relatives with ovarian cancer.[8] The risk is somewhat less for women who have one first-degree and one second-degree relative (grandmother or aunt) with ovarian cancer.
Common [[risk factors]] in the development of [[ovarian cancer]] include:<ref>{{Cite journal
 
| author = [[A. Daniilidis]] & [[V. Karagiannis]]
 
| title = Epithelial ovarian cancer. Risk factors, screening and the role of prophylactic oophorectomy
==Known risk factors==
| journal = [[Hippokratia]]
 
| volume = 11
There is convincing evidence that the following factors increase your risk of developing epithelial ovarian cancer and tumours of borderline malignancy.
| issue = 2
 
| pages = 63–66
Family history of ovarian cancer===
| year = 2007
 
| month = April
Sometimes more cases of ovarian cancer develop in a family than would be expected by chance. A family history of ovarian cancer means that one or more close blood relatives have or had ovarian cancer. Sometimes it is not clear whether the family’s pattern of cancer is due to chance, shared lifestyle factors, a genetic risk passed from parents to children or a combination of these factors.
| pmid = 19582179
 
}}</ref>
Having several relatives who have ovarian cancer can increase your risk of ovarian cancer. About 5%–10% of women with ovarian cancer have a family member who also has this disease. Having relatives with ovarian cancer on either your mother’s or your father’s side of the family increases your risk.
 
The risk of developing ovarian cancer is increased if:
 
One first-degree relative (mother, sister or daughter) has ovarian cancer, especially if they were diagnosed with ovarian cancer before the age of 50 or before they went into menopause. Women who have a mother diagnosed with ovarian cancer are at a higher risk than women who have a daughter diagnosed with ovarian cancer.
Two or more first-degree relatives have been diagnosed with ovarian cancer.
One first-degree relative and one second-degree relative (aunt, grandmother or niece) have been diagnosed with ovarian cancer. This combination means you have a slightly higher risk for ovarian cancer.
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===BRCA gene mutations===
 
Only a small number of ovarian cancers (about 5%–10%) are related to a specific inherited genetic abnormality. Breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) normally help control the growth of cancer cells. BRCA gene mutations were first found in women with breast cancer. They also increase the risk of ovarian cancer. These mutations can be inherited from either parent.
 
While mutations in BRCA1 or BRCA2 genes increase the risk of ovarian cancer, not all women with mutations in these genes will develop ovarian cancer.
 
Overall, BRCA1 increases the risk of ovarian cancer more than BRCA2. Ovarian cancer is more likely to occur before age 50 in women with BRCA1 mutations. Ovarian cancer is more likely to occur after age 60 in women with BRCA2 mutations.
 
BRCA gene mutations may be suspected in families if:
 
Ovarian cancer occurs in 3 or more first-degree relatives (mother, sisters or daughters).
Breast or ovarian cancer develops at a younger age in several first-degree relatives, including at least 2 relatives who have breast cancer and 2 who have ovarian cancer.
Ovarian cancers related to BRCA gene mutations are different from ovarian cancers in the general population of women (sporadic ovarian cancer). These cases of ovarian cancer are typically diagnosed at a younger age. The average age of diagnosis is 48 years for genetic forms, compared to 52 years for sporadic ovarian cancer.
 
Serous epithelial tumours are more commonly linked to BRCA gene mutations than sporadic forms of ovarian cancer. Having ovarian cancer linked to a BRCA gene mutation also increases the risk of developing papillary serous carcinoma of the peritoneum, which is a cancer in the lining of the abdominal cavity. But there may be a more favourable prognosis for forms of the disease linked to BRCA gene mutations.
 
Women with ovarian cancer related to a BRCA gene mutation are also at higher than average risk of developing breast and other cancers. Talk to your doctor about your risks. Genetic risk assessment and genetic testing may be an option for some women.
 
 
 
===Lynch syndrome===
 
Lynch syndrome (also called hereditary non-polyposis colorectal cancer, or HNPCC) is an uncommon genetic condition that increases the risk of colorectal and other cancers, including ovarian cancer. Women with type B Lynch syndrome, or Lynch II, have a higher risk of developing epithelial ovarian cancer in their lifetime.
 
 
 
===Nullipara===
 
Women who have never been pregnant have a higher risk of developing ovarian cancer than women who have been pregnant. Researchers are not sure if the lower risk in women who have been pregnant is due to the hormones that are present during pregnancy, which may have a protective effect. It is also unclear if the higher risk in women who have never been pregnant is linked to the factors that may make it difficult for her to become pregnant.
 
The risk for ovarian cancer is also higher in women who have never given birth (nulliparous), whether or not they have ever been pregnant. Researchers are not sure if this increased risk is related to the same factors that increase the risk of ovarian cancer in women who have never been pregnant.
 
 
 
===Family history of certain cancers===
 
Women who have a family history of breast cancer have a higher risk of developing ovarian cancer. A strong family history of uterine cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch II syndrome), which confers a higher risk for developing ovarian cancer.
 
 
===Personal history of breast cancer===
 
Women who have been diagnosed with breast cancer have a higher risk of developing ovarian cancer. This could be because of a BRCA gene mutation. Some of the same risk factors for breast cancer that are related to a woman's menstruation history may also increase her risk of developing ovarian cancer. These risk factors include starting your period at an early age (younger than 11) or starting menopause at a later age (after age 55).
 
 
===Ashkenazi Jewish ancestry===
 
Studies have shown that women of Ashkenazi Jewish descent (Eastern European ancestry) are more likely than women in the general population to carry mutations of the BRCA1 and BRCA2 genes. About 1 in 40 Ashkenazi Jewish women carry a BRCA gene mutation, while 1 in 500 women in the general population have the gene mutation. Women with these mutations have a higher chance of developing ovarian cancer.
 
 
===Hormone replacement therapy===
 
Hormone replacement therapy (HRT) is used to manage the symptoms of menopause, such as hot flashes, vaginal dryness and mood swings. Research shows that using estrogen alone as HRT increases the risk of ovarian cancer. This risk increases with the length of time that the woman takes estrogen.
 
It is not clear if HRT that uses both estrogen and progestin (combined HRT) increases the risk for ovarian cancer.
 
 
===Smoking===
 
Smoking increases a woman’s risk of developing mucinous epithelial tumours of the ovary.
 
 
===Asbestos===
 
Studies have found that women who are heavily exposed to asbestos, especially in the workplace, are at an increased risk of developing ovarian cancer. Other studies have shown that asbestos fibres can accumulate in the ovaries of women exposed to it.
 
 
==Possible risk factors==
 
The following factors have been linked with ovarian cancer, but there is not enough evidence to say they are known risk factors. Further study is needed to clarify the role of these factors for ovarian cancer.
 
===Being obese===
 
Being obese means having a body mass index, or BMI, of 30 or more. Some studies have shown that being obese may slightly increase the risk of developing ovarian cancer.
 
===Using talc on the genitals===
 
Research studies on the use of talc on the genital, or perineal, area and the risk of ovarian cancer have had mixed results. Some studies show an increased risk, while others do not. Some research suggests that in the past certain sources of talcum powder may have been contaminated with asbestos or may have contained asbestiform fibres, which are fibres that have similar properties as asbestos. Health Canada now ensures that talcum powder does not contain asbestos. Talcum powders made with cornstarch do not increase the risk of ovarian cancer.
 
===Endometriosis===
 
The endometrium is the lining of the uterus. Endometriosis occurs when the endometrium grows outside of the uterus. It can grow on the ovaries, behind the uterus or on the intestines (bowels) or bladder. A recent Canadian study suggested that ovarian cancer and endometriosis may have a similar origin. Other studies have suggested that a woman’s risk of developing ovarian cancer may be higher if she has endometriosis, especially if the endometriosis involves the ovaries. Other studies have shown that the risk of certain types of ovarian cancer, including clear cell and endometrioid tumours, may be higher in women with endometriosis.
 
Tall adult height
 
Studies have shown that tall women have a slightly higher risk of ovarian cancer. Researchers think this increased risk may be due to growth and puberty hormones, rather than being tall by itself.
 


{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF| Ovarian cancer risk factors}}
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF| Characterestics}}
! style="background: #4479BA; padding: 5px 5px;" rowspan=1 | {{fontcolor|#FFFFFF| description}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="17;" | [[Known risk factors]] <ref>{{cite journal|doi=10.22034/APJCP.2017.18.1.11}}</ref><ref name="pmid17416853" /><ref name="pmid162849912" /><ref name="pmid9579428" /><ref name="pmid21324516" /><ref name="pmid26720728" /><ref name="pmid17005245" /><ref name="pmid12820486" /><ref name="pmid22223086" /><ref name="pmid19390450" /><ref name="pmid12711737" />
| style="padding: 5px 5px; background: #F5F5F5;" | [[Age]]
| style="padding: 5px 5px; background: #F5F5F5;" | As age increases, [[ovarian cancer]] [[incidence]] increases.
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Hormonal and reproductive factors]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Early menarche and late menopause]], [[Nulliparity]], Infertility
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Early menarche and late menopause]]
| style="padding: 5px 5px; background: #F5F5F5;" |Both increase the frequency of the [[ovulation]] and the ovarian [[epithelium]] exposure to persistent injury
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Nulliparity
| style="padding: 5px 5px; background: #F5F5F5;" |Studies have shown that [[Multiple pregnancy|multiparity]] and full-term [[pregnancies]] decrease the risk of [[ovarian cancer]]  and [[Fallopian tube cancer|fallopian tubal carcinoma]]
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Infertility]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Infertility]] is an independent risk factor of [[ovarian cancer]]
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[ Endometriosis ]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Ovarian cancer|Ovarian cancers]] that arise from [[Endometriosis|endometriotic tissue]] usually affect young women and have better [[prognosis]] and [[survival rates]]
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Polycystic ovarian syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" |The association is controversial and complex
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Postmenopausal hormone therapy]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Estrogen]] therapy alone has more association with ovarian cancer than combined [[estrogen]]-[[Progesterone|progesteron]] therapy
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Intrauterine device]]
| style="padding: 5px 5px; background: #F5F5F5;" |Regardless of the type of the [[IUD|IUD,]] studies have shown an increased risk of [[ovarian cancer]] with [[IUD]] use
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Genetic factors]]
| style="padding: 5px 5px; background: #F5F5F5;" |
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[BRCA gene mutations]]
| style="padding: 5px 5px; background: #F5F5F5;" |The risk is more with '''[[BRCA1]]''' carriers than '''[[BRCA2]]''' carriers. [[Ovarian cancer]] develops at an earlier age in [[BRCA1]]-carrier women compared to [[BRCA2]]-carrier women. [[Serous]] [[adenocarcinoma]] is the most common type.General women and women with [[BRCA]] [[mutations]] usually present with stage III or IV
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Lynch syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" |'''[[Hereditary nonpolyposis colorectal cancer]] ([[HNPCC]])''' : 1 percent of cases with [[ovarian cancer]] have [[Lynch syndrome]].
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Other genetic factors]]
| style="padding: 5px 5px; background: #F5F5F5;" |The genes in the [[Fanconi anemia|Fanconi anemias]] pathway can undergo different mutations and lead to the development of [[ovarian]] and/or [[breast cancer]]. The genes that are associated with [[ovarian cancer]] are: '''[[BRCA1]], [[BRCA2]], [[BRIP1]], [[RAD51C]], RAD51D, [[PALB2]], and [[BARD1]]'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Family history of certain cancers]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[BRCA]] mutation carriers with personal or family history of [[breast cancer]] have higher risk of developing [[ovarian cancer]] that those without [[BRCA]] mutation
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Personal history of breast cancer]]
| style="padding: 5px 5px; background: #F5F5F5;" |Increases the risk of breast-ovarian syndrome
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Environmental factors]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Cigarette smoking]] associated with [[mucinous]] [[ovarian cancer]], [[asbestos]],[[Talcum powder|Talc]] (Its association is controversial).
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Other factors]]
| style="padding: 5px 5px; background: #F5F5F5;" |Diet: [[dairy]] food with high animal fat intake is claimed to be associated with [[ovarian cancer]] but data are not sufficient to confirm this association, exercise: No clear evidence about the association between physical activity and [[breast cancer]], and [[obesity]]: can increases the risk of [[ovarian cancer]] and the risk of its [[mortality]], [[Pelvic inflammatory disease]] can increase the risk of and might be used as [[tumor marker]] for [[ovarian tumor]].
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="2;" |Possible risk factors<ref name="pmid12711737" /><ref name="pmid12820486" />
| style="padding: 5px 5px; background: #F5F5F5;" | [[Obesity]]
| style="padding: 5px 5px; background: #F5F5F5;" |Can increases the risk of [[ovarian cancer]] and the risk of its [[mortality]].
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Talc use on genetals]]
| style="padding: 5px 5px; background: #F5F5F5;" |Its association is controversial).
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="3;" |Unknown risk factors<ref name="pmid22223086" /><ref name="pmid8816606">{{cite journal| author=Bristow RE, Karlan BY| title=Ovulation induction, infertility, and ovarian cancer risk. | journal=Fertil Steril | year= 1996 | volume= 66 | issue= 4 | pages= 499-507 | pmid=8816606 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8816606  }}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" | [[Food types and amount]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Dairy]] food with high animal fat intake is claimed to be associated with [[ovarian cancer]] but data are not sufficient to confirm this association
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fertility drugs]]
| style="padding: 5px 5px; background: #F5F5F5;" |The role of medications used for [[ovulation]] [[induction]] in increasing the risks of [[ovarian cancer]] is controversial. The association between the [[fertility]] drugs and [[ovarian cancer]] could be due to the stimulating effect of these drug, however this association is not a causal relation
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Sedentary life]]
| style="padding: 5px 5px; background: #F5F5F5;" |Its association is unknown
|-
|}


* Common risk factors in the development of [[ovarian cancer]] include:
**'''Age:'''
***There is a proportional association between age and [[ovarian cancer]], as age increases, [[ovarian cancer]] [[incidence]] increases.<ref name="pmid19910378">{{cite journal| author=Gates MA, Rosner BA, Hecht JL, Tworoger SS| title=Risk factors for epithelial ovarian cancer by histologic subtype. | journal=Am J Epidemiol | year= 2010 | volume= 171 | issue= 1 | pages= 45-53 | pmid=19910378 | doi=10.1093/aje/kwp314 | pmc=2796984 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19910378  }} </ref>
**'''Hormonal and reproductive factors:'''
***'''Early [[menarche]] and late [[menopause|menopau]]'''[[menopause|se]]:
****Both increase the frequency of the [[ovulation]] and the ovarian [[epithelium]] exposure to persistent injury.<ref name="pmid19910378" /><ref name="pmid21915124">{{cite journal| author=Tsilidis KK, Allen NE, Key TJ, Dossus L, Lukanova A, Bakken K et al.| title=Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition. | journal=Br J Cancer | year= 2011 | volume= 105 | issue= 9 | pages= 1436-42 | pmid=21915124 | doi=10.1038/bjc.2011.371 | pmc=3241548 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21915124  }}</ref>
***[[Parity|'''Nulliparity''']]
****Studies have shown that [[Multiple pregnancy|multiparity]] and [[full term]] [[pregnancies]] decrease the risk of [[ovarian cancer]]  and [[Fallopian tube cancer|fallopian tubal carcinoma]].<ref name="pmid23116937">{{cite journal| author=Stewart LM, Holman CD, Aboagye-Sarfo P, Finn JC, Preen DB, Hart R| title=In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk. | journal=Gynecol Oncol | year= 2013 | volume= 128 | issue= 2 | pages= 260-4 | pmid=23116937 | doi=10.1016/j.ygyno.2012.10.023 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23116937  }}</ref><ref name="pmid11237375">{{cite journal| author=Titus-Ernstoff L, Perez K, Cramer DW, Harlow BL, Baron JA, Greenberg ER| title=Menstrual and reproductive factors in relation to ovarian cancer risk. | journal=Br J Cancer | year= 2001 | volume= 84 | issue= 5 | pages= 714-21 | pmid=11237375 | doi=10.1054/bjoc.2000.1596 | pmc=2363792 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11237375  }}</ref>
***'''[[Infertility]]:'''
***Type of [[infertility]] and its causes should be taken in consideration as different causes can increase the risk of [[ovarian cancer]] such as:<ref name="pmid15302291">{{cite journal| author=Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE et al.| title=Ovarian cancer risk associated with varying causes of infertility. | journal=Fertil Steril | year= 2004 | volume= 82 | issue= 2 | pages= 405-14 | pmid=15302291 | doi=10.1016/j.fertnstert.2004.02.109 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15302291  }}</ref>
****Primary [[infertility]]
****Secondary [[infertility]] as [[endometriosis]]
****The role of medications used for [[ovulation]] [[induction]] in increasing the risks of [[ovarian cancer]] is controversial. The association between the [[fertility]] drugs and [[ovarian cancer]] could be due to the stimulating effect of these drug, however this association is not a causal relation.<ref name="pmid8816606" />
****Regardless to the [[fertility]] medications use, [[infertility]] is an independent risk factor of [[ovarian cancer]].<ref name="pmid8816606" />
***'''[[Endometriosis]]'''
****[[Ovarian cancers]] that arise from [[Endometriosis|endometriotic tissue]] usually affect young women and have better [[prognosis]] and [[survival rates]].<ref name="pmid11585420">{{cite journal| author=Erzen M, Rakar S, Klancnik B, Syrjänen K, Klancar B| title=Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. | journal=Gynecol Oncol | year= 2001 | volume= 83 | issue= 1 | pages= 100-8 | pmid=11585420 | doi=10.1006/gyno.2001.6382 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11585420  }}</ref>
***'''[[Polycystic ovarian syndrome]]:'''
****The association is controversial and complex. [[Meta-analysis]] found an  association between [[PCOS]] and [[endometrial cancer]] in general but not with [[ovarian cancer]] specifically.<ref name="pmid24688118">{{cite journal| author=Barry JA, Azizia MM, Hardiman PJ| title=Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. | journal=Hum Reprod Update | year= 2014 | volume= 20 | issue= 5 | pages= 748-58 | pmid=24688118 | doi=10.1093/humupd/dmu012 | pmc=4326303 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24688118  }}</ref>
***'''[[Postmenopausal]] [[hormone]] [[therapy]]''':
****A non statistical significant association found between combined [[estrogen]]-[[Progesterone|progesteron]] therapy and [[ovarian carcinoma]].<ref name="pmid14519708">{{cite journal| author=Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M et al.| title=Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. | journal=JAMA | year= 2003 | volume= 290 | issue= 13 | pages= 1739-48 | pmid=14519708 | doi=10.1001/jama.290.13.1739 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14519708  }}</ref>
****[[Meta-analysis]] found small significant association between [[ovarian cancer]] and [[estrogen]] therapy alone.<ref name="pmid18221779">{{cite journal| author=Zhou B, Sun Q, Cong R, Gu H, Tang N, Yang L et al.| title=Hormone replacement therapy and ovarian cancer risk: a meta-analysis. | journal=Gynecol Oncol | year= 2008 | volume= 108 | issue= 3 | pages= 641-51 | pmid=18221779 | doi=10.1016/j.ygyno.2007.12.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18221779  }}</ref>
***'''[[Intrauterine device]]:'''
****Regardless of the type of the [[IUD|IUD,]] studies have shown an increased risk of [[ovarian cancer]] with [[IUD]] use.<ref name="pmid17656616">{{cite journal| author=Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE| title=Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. | journal=Am J Epidemiol | year= 2007 | volume= 166 | issue= 8 | pages= 894-901 | pmid=17656616 | doi=10.1093/aje/kwm157 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17656616  }}</ref>
**'''[[Genetic]] factors'''
***'''[[BRCA]] [[gene]] [[mutations]]''': the risk of both [[ovarian]] and [[breast]] [[cancers]] increases in women with [[BRCA]] [[mutations]].
***The risk is more with '''[[BRCA1]]''' carriers than '''[[BRCA2]]''' carriers.<ref name="pmid17416853">{{cite journal| author=Chen S, Parmigiani G| title=Meta-analysis of BRCA1 and BRCA2 penetrance. | journal=J Clin Oncol | year= 2007 | volume= 25 | issue= 11 | pages= 1329-33 | pmid=17416853 | doi=10.1200/JCO.2006.09.1066 | pmc=2267287 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17416853  }}</ref>
***[[Ovarian cancer]] develops at an earlier age in [[BRCA1]]-carrier women compared to [[BRCA2]]-carrier women. [[Serous]] [[adenocarcinoma]] is the most common type.<ref name="pmid162849912">{{cite journal| author=Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H et al.| title=BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. | journal=Cancer | year= 2005 | volume= 104 | issue= 12 | pages= 2807-16 | pmid=16284991 | doi=10.1002/cncr.21536 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16284991  }}</ref>
***General women and women with [[BRCA]] [[mutations]] usually present with stage III or IV.<ref name="pmid16284991">{{cite journal| author=Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H et al.| title=BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. | journal=Cancer | year= 2005 | volume= 104 | issue= 12 | pages= 2807-16 | pmid=16284991 | doi=10.1002/cncr.21536 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16284991  }}</ref>
***However, the grade is higher in women who are [[BRCA]] [[mutations]]' carries.<ref name="pmid15073127">{{cite journal| author=Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Merrett S et al.| title=Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. | journal=Clin Cancer Res | year= 2004 | volume= 10 | issue= 7 | pages= 2473-81 | pmid=15073127 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15073127  }}</ref>
***The short-term [[survival rate]] of [[ovarian cancer]] in women with [[BRCA]] [[mutations]] is higher than non-carriers.<ref name="pmid22274685">{{cite journal| author=Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY et al.| title=Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. | journal=JAMA | year= 2012 | volume= 307 | issue= 4 | pages= 382-90 | pmid=22274685 | doi=10.1001/jama.2012.20 | pmc=3727895 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22274685  }}</ref>
***[[Prophylactic]] [[bilateral]] [[salpingo-oophorectomy]] can be done in [[BRCA]] [[mutation]] carries who are at higher risk of developing [[fallopian tube cancer]] and primary [[Peritoneal carcinomatosis|peritoneal carcinoma]].<ref name="pmid14615451">{{cite journal| author=Levine DA, Argenta PA, Yee CJ, Marshall DS, Olvera N, Bogomolniy F et al.| title=Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations. | journal=J Clin Oncol | year= 2003 | volume= 21 | issue= 22 | pages= 4222-7 | pmid=14615451 | doi=10.1200/JCO.2003.04.131 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14615451  }}</ref>
**[[Lynch syndrome|'''Lynch syndrome''']] or '''[[hereditary nonpolyposis colorectal cancer]] ([[HNPCC]])''' :
***1 percent of cases with [[ovarian cancer]] have [[Lynch syndrome]].<ref name="pmid9579428">{{cite journal| author=Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR et al.| title=BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. | journal=Am J Obstet Gynecol | year= 1998 | volume= 178 | issue= 4 | pages= 670-7 | pmid=9579428 | doi=10.1016/s0002-9378(98)70476-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9579428  }}</ref>
**'''Family history of [[breast cancer]]''':
***It is not clear whether the family’s pattern of cancer is due to chance, shared lifestyle factors, a genetic risk passed from parents to children or a combination of these factors.
***By American cancer society, about 5 to 10% of ovarian cancers are a part of family cancer syndromes resulting from inherited changes (''mutations'') in certain genes.
***[[BRCA]] mutation carriers with personal or family history of [[breast cancer]] have higher risk of developing [[ovarian cancer]] that those without [[BRCA]] mutation<ref name="pmid16174860">{{cite journal| author=Kauff ND, Mitra N, Robson ME, Hurley KE, Chuai S, Goldfrank D et al.| title=Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families. | journal=J Natl Cancer Inst | year= 2005 | volume= 97 | issue= 18 | pages= 1382-4 | pmid=16174860 | doi=10.1093/jnci/dji281 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16174860  }}</ref>
**'''Other [[genetic]] factors''':
***The genes in the [[Fanconi anemia|Fanconi anemias]] pathway can undergo different mutations and lead to the development of [[ovarian]] and/or [[breast cancer]]<ref name="pmid21324516">{{cite journal| author=Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA et al.| title=Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | journal=Gynecol Oncol | year= 2011 | volume= 121 | issue= 2 | pages= 353-7 | pmid=21324516 | doi=10.1016/j.ygyno.2011.01.020 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21324516  }}</ref>. The genes that are associated with [[ovarian cancer]] are: '''[[BRCA1]], [[BRCA2]], [[BRIP1]], [[RAD51C]], RAD51D, [[PALB2]], and [[BARD1]]'''<ref name="pmid26720728">{{cite journal| author=Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S et al.| title=Inherited Mutations in Women With Ovarian Carcinoma. | journal=JAMA Oncol | year= 2016 | volume= 2 | issue= 4 | pages= 482-90 | pmid=26720728 | doi=10.1001/jamaoncol.2015.5495 | pmc=4845939 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26720728  }}</ref>
**[[Environmental factor|'''Environmental factors''']] such as:
***[[Cigarette smoking]] associated with [[mucinous]] [[ovarian cancer]]<ref name="pmid17005245">{{cite journal| author=Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM| title=Does smoking increase risk of ovarian cancer? A systematic review. | journal=Gynecol Oncol | year= 2006 | volume= 103 | issue= 3 | pages= 1122-9 | pmid=17005245 | doi=10.1016/j.ygyno.2006.08.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17005245  }}</ref>
***[[Asbestos]],[[Talcum powder|Talc]] (Its association is controversial)<ref name="pmid12820486">{{cite journal| author=Huncharek M, Geschwind JF, Kupelnick B| title=Perineal application of cosmetic talc and risk of invasive epithelial ovarian cancer: a meta-analysis of 11,933 subjects from sixteen observational studies. | journal=Anticancer Res | year= 2003 | volume= 23 | issue= 2C | pages= 1955-60 | pmid=12820486 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12820486  }}</ref>
**'''Other factors''' such as:
***Diet:
****[[dairy|Ddairy]] food with high animal fat intake is claimed to be associated with [[ovarian cancer]] but data are not sufficient to confirm this association.<ref name="pmid22223086">{{cite journal| author=Blank MM, Wentzensen N, Murphy MA, Hollenbeck A, Park Y| title=Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study. | journal=Br J Cancer | year= 2012 | volume= 106 | issue= 3 | pages= 596-602 | pmid=22223086 | doi=10.1038/bjc.2011.572 | pmc=3273348 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22223086  }}</ref>
***Exercise:
****No clear evidence about the association between physical activity and [[breast cancer]].<ref name="pmid19390450">{{cite journal| author=Carnide N, Kreiger N, Cotterchio M| title=Association between frequency and intensity of recreational physical activity and epithelial ovarian cancer risk by age period. | journal=Eur J Cancer Prev | year= 2009 | volume= 18 | issue= 4 | pages= 322-30 | pmid=19390450 | doi=10.1097/CEJ.0b013e32832bf3fa | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19390450  }}</ref>
***[[Obesity]]:
****Can increases the risk of [[ovarian cancer]] and the risk of its [[mortality]].<ref name="pmid12711737">{{cite journal| author=Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ| title=Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 17 | pages= 1625-38 | pmid=12711737 | doi=10.1056/NEJMoa021423 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12711737  }}</ref>
**[[Pelvic inflammatory disease]] can increase the risk of and might be used as [[tumor marker]] for [[ovarian tumor]]<ref name="pmid21835693">{{cite journal| author=Lin HW, Tu YY, Lin SY, Su WJ, Lin WL, Lin WZ et al.| title=Risk of ovarian cancer in women with pelvic inflammatory disease: a population-based study. | journal=Lancet Oncol | year= 2011 | volume= 12 | issue= 9 | pages= 900-4 | pmid=21835693 | doi=10.1016/S1470-2045(11)70165-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21835693  }}</ref>


== References ==
== References ==
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{{WS}}
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[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
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Latest revision as of 15:29, 12 September 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Huda A. Karman, M.D.

Overview

The risk of developing ovarian cancer appears to be affected by several factors; in fact, early age at first pregnancy, older ages of final pregnancy, and the use of low dose hormonal contraception have been associated with a lower incidence of ovarian cancer. There is good evidence that in some women genetic factors are important.

Risk Factors

Common risk factors in the development of ovarian cancer include:[1]

Ovarian cancer risk factors Characterestics description
Known risk factors [2][3][4][5][6][7][8][9][10][11][12] Age As age increases, ovarian cancer incidence increases.
Hormonal and reproductive factors Early menarche and late menopause, Nulliparity, Infertility
Early menarche and late menopause Both increase the frequency of the ovulation and the ovarian epithelium exposure to persistent injury
Nulliparity Studies have shown that multiparity and full-term pregnancies decrease the risk of ovarian cancer and fallopian tubal carcinoma
Infertility Infertility is an independent risk factor of ovarian cancer
Endometriosis Ovarian cancers that arise from endometriotic tissue usually affect young women and have better prognosis and survival rates
Polycystic ovarian syndrome The association is controversial and complex
Postmenopausal hormone therapy Estrogen therapy alone has more association with ovarian cancer than combined estrogen-progesteron therapy
Intrauterine device Regardless of the type of the IUD, studies have shown an increased risk of ovarian cancer with IUD use
Genetic factors
BRCA gene mutations The risk is more with BRCA1 carriers than BRCA2 carriers. Ovarian cancer develops at an earlier age in BRCA1-carrier women compared to BRCA2-carrier women. Serous adenocarcinoma is the most common type.General women and women with BRCA mutations usually present with stage III or IV
Lynch syndrome Hereditary nonpolyposis colorectal cancer (HNPCC) : 1 percent of cases with ovarian cancer have Lynch syndrome.
Other genetic factors The genes in the Fanconi anemias pathway can undergo different mutations and lead to the development of ovarian and/or breast cancer. The genes that are associated with ovarian cancer are: BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, PALB2, and BARD1
Family history of certain cancers BRCA mutation carriers with personal or family history of breast cancer have higher risk of developing ovarian cancer that those without BRCA mutation
Personal history of breast cancer Increases the risk of breast-ovarian syndrome
Environmental factors Cigarette smoking associated with mucinous ovarian cancer, asbestos,Talc (Its association is controversial).
Other factors Diet: dairy food with high animal fat intake is claimed to be associated with ovarian cancer but data are not sufficient to confirm this association, exercise: No clear evidence about the association between physical activity and breast cancer, and obesity: can increases the risk of ovarian cancer and the risk of its mortality, Pelvic inflammatory disease can increase the risk of and might be used as tumor marker for ovarian tumor.
Possible risk factors[12][9] Obesity Can increases the risk of ovarian cancer and the risk of its mortality.
Talc use on genetals Its association is controversial).
Unknown risk factors[10][13] Food types and amount Dairy food with high animal fat intake is claimed to be associated with ovarian cancer but data are not sufficient to confirm this association
Fertility drugs The role of medications used for ovulation induction in increasing the risks of ovarian cancer is controversial. The association between the fertility drugs and ovarian cancer could be due to the stimulating effect of these drug, however this association is not a causal relation
Sedentary life Its association is unknown

References

  1. A. Daniilidis & V. Karagiannis (2007). "Epithelial ovarian cancer. Risk factors, screening and the role of prophylactic oophorectomy". Hippokratia. 11 (2): 63–66. PMID 19582179. Unknown parameter |month= ignored (help)
  2. . doi:10.22034/APJCP.2017.18.1.11. Missing or empty |title= (help)
  3. 3.0 3.1 Chen S, Parmigiani G (2007). "Meta-analysis of BRCA1 and BRCA2 penetrance". J Clin Oncol. 25 (11): 1329–33. doi:10.1200/JCO.2006.09.1066. PMC 2267287. PMID 17416853.
  4. 4.0 4.1 Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H; et al. (2005). "BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases". Cancer. 104 (12): 2807–16. doi:10.1002/cncr.21536. PMID 16284991.
  5. 5.0 5.1 Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR; et al. (1998). "BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing". Am J Obstet Gynecol. 178 (4): 670–7. doi:10.1016/s0002-9378(98)70476-4. PMID 9579428.
  6. 6.0 6.1 Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA; et al. (2011). "Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer". Gynecol Oncol. 121 (2): 353–7. doi:10.1016/j.ygyno.2011.01.020. PMID 21324516.
  7. 7.0 7.1 Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S; et al. (2016). "Inherited Mutations in Women With Ovarian Carcinoma". JAMA Oncol. 2 (4): 482–90. doi:10.1001/jamaoncol.2015.5495. PMC 4845939. PMID 26720728.
  8. 8.0 8.1 Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM (2006). "Does smoking increase risk of ovarian cancer? A systematic review". Gynecol Oncol. 103 (3): 1122–9. doi:10.1016/j.ygyno.2006.08.012. PMID 17005245.
  9. 9.0 9.1 9.2 Huncharek M, Geschwind JF, Kupelnick B (2003). "Perineal application of cosmetic talc and risk of invasive epithelial ovarian cancer: a meta-analysis of 11,933 subjects from sixteen observational studies". Anticancer Res. 23 (2C): 1955–60. PMID 12820486.
  10. 10.0 10.1 10.2 Blank MM, Wentzensen N, Murphy MA, Hollenbeck A, Park Y (2012). "Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study". Br J Cancer. 106 (3): 596–602. doi:10.1038/bjc.2011.572. PMC 3273348. PMID 22223086.
  11. 11.0 11.1 Carnide N, Kreiger N, Cotterchio M (2009). "Association between frequency and intensity of recreational physical activity and epithelial ovarian cancer risk by age period". Eur J Cancer Prev. 18 (4): 322–30. doi:10.1097/CEJ.0b013e32832bf3fa. PMID 19390450.
  12. 12.0 12.1 12.2 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003). "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults". N Engl J Med. 348 (17): 1625–38. doi:10.1056/NEJMoa021423. PMID 12711737.
  13. 13.0 13.1 13.2 Bristow RE, Karlan BY (1996). "Ovulation induction, infertility, and ovarian cancer risk". Fertil Steril. 66 (4): 499–507. PMID 8816606.
  14. 14.0 14.1 Gates MA, Rosner BA, Hecht JL, Tworoger SS (2010). "Risk factors for epithelial ovarian cancer by histologic subtype". Am J Epidemiol. 171 (1): 45–53. doi:10.1093/aje/kwp314. PMC 2796984. PMID 19910378.
  15. Tsilidis KK, Allen NE, Key TJ, Dossus L, Lukanova A, Bakken K; et al. (2011). "Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition". Br J Cancer. 105 (9): 1436–42. doi:10.1038/bjc.2011.371. PMC 3241548. PMID 21915124.
  16. Stewart LM, Holman CD, Aboagye-Sarfo P, Finn JC, Preen DB, Hart R (2013). "In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk". Gynecol Oncol. 128 (2): 260–4. doi:10.1016/j.ygyno.2012.10.023. PMID 23116937.
  17. Titus-Ernstoff L, Perez K, Cramer DW, Harlow BL, Baron JA, Greenberg ER (2001). "Menstrual and reproductive factors in relation to ovarian cancer risk". Br J Cancer. 84 (5): 714–21. doi:10.1054/bjoc.2000.1596. PMC 2363792. PMID 11237375.
  18. Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE; et al. (2004). "Ovarian cancer risk associated with varying causes of infertility". Fertil Steril. 82 (2): 405–14. doi:10.1016/j.fertnstert.2004.02.109. PMID 15302291.
  19. Erzen M, Rakar S, Klancnik B, Syrjänen K, Klancar B (2001). "Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study". Gynecol Oncol. 83 (1): 100–8. doi:10.1006/gyno.2001.6382. PMID 11585420.
  20. Barry JA, Azizia MM, Hardiman PJ (2014). "Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis". Hum Reprod Update. 20 (5): 748–58. doi:10.1093/humupd/dmu012. PMC 4326303. PMID 24688118.
  21. Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M; et al. (2003). "Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial". JAMA. 290 (13): 1739–48. doi:10.1001/jama.290.13.1739. PMID 14519708.
  22. Zhou B, Sun Q, Cong R, Gu H, Tang N, Yang L; et al. (2008). "Hormone replacement therapy and ovarian cancer risk: a meta-analysis". Gynecol Oncol. 108 (3): 641–51. doi:10.1016/j.ygyno.2007.12.003. PMID 18221779.
  23. Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE (2007). "Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk". Am J Epidemiol. 166 (8): 894–901. doi:10.1093/aje/kwm157. PMID 17656616.
  24. Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H; et al. (2005). "BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases". Cancer. 104 (12): 2807–16. doi:10.1002/cncr.21536. PMID 16284991.
  25. Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Merrett S; et al. (2004). "Pathology of ovarian cancers in BRCA1 and BRCA2 carriers". Clin Cancer Res. 10 (7): 2473–81. PMID 15073127.
  26. Bolton KL, Chenevix-Trench G, Goh C, Sadetzki S, Ramus SJ, Karlan BY; et al. (2012). "Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer". JAMA. 307 (4): 382–90. doi:10.1001/jama.2012.20. PMC 3727895. PMID 22274685.
  27. Levine DA, Argenta PA, Yee CJ, Marshall DS, Olvera N, Bogomolniy F; et al. (2003). "Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations". J Clin Oncol. 21 (22): 4222–7. doi:10.1200/JCO.2003.04.131. PMID 14615451.
  28. Kauff ND, Mitra N, Robson ME, Hurley KE, Chuai S, Goldfrank D; et al. (2005). "Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families". J Natl Cancer Inst. 97 (18): 1382–4. doi:10.1093/jnci/dji281. PMID 16174860.
  29. Lin HW, Tu YY, Lin SY, Su WJ, Lin WL, Lin WZ; et al. (2011). "Risk of ovarian cancer in women with pelvic inflammatory disease: a population-based study". Lancet Oncol. 12 (9): 900–4. doi:10.1016/S1470-2045(11)70165-6. PMID 21835693.

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