Family History Of Endometrial Cancer Research Articles

Impact of estradiol in inducing endometrial cancer using RL95-2

BackgroundEndometrial cancer is the most common gynecological malignancy that originates from the inner lining of the uterus and predominantly affects postmenopausal women. Prolonged exposure to estrogen, family history of endometrial cancer, obesity, and hormonal imbalance are some of the risk factors associated with endometrial cancer. In our study, we investigated the effect of estradiol, a potent form of estrogen at various concentrations on endometrial cell line RL95–2. MethodsEndometrial cell RL95–2 were cultured in DMEM medium with optimal conditions required to maintain the cells. MTT assay and colony formation assay were further performed after treating the cells with different concentrations of estradiol (1, 10, and 100 nM) and TAM (100 nM). Moreover, the effect of genes regulated by estradiol was also examined using microarray and validated using real-time polymerase chain reaction (qRT-PCR). ResultsTime-dependent MTT assay shows a significant change in the ability of the cells to survive relative to concentrations. Colony formation was found to be directly proportional to the concentration of the estradiol (p < 0.05). Among genes, MMP14 (p = 0.03), SPARCL1 (p = 0.005), and CLU (p = 0.06) showed a significant up-regulation in their expression after estradiol treatment while NRN1 (p < 0.001) showed significant downregulation in expression pattern compared to control. However, the TAM treatment was found to be significantly effective after 72 h (p < 0.001) compared to control and 100 nM E2 (p = 0.0206). ConclusionOur study suggests that estradiol significantly contributes to regulating the viability, colony formation, and expression of genes associated with endometrial cancer.

Description of Endometrial Cancer Epidemiology at Sabratha National Cancer Institute, Western Libya: A 3-Year Data Analysis

Background: Endometrial cancer is the sixth most common cancer in women worldwide and the most frequent gynecological cancer in developed countries. Endometrial cancer mortality rates are high in low- and middle-income countries. Objectives: The current study aims to provide valuable insights into the epidemiology of endometrial cancer at Sabartha cancer institute over three-years periods, with the goal of identifying trends, risk factors, and potential areas for intervention. Methodology: This study is descriptive study, using data which were collected from the all primary endometrial cancers that were diagnosed or treated in the Sabratha National Cancer Institute,Western Libya. The data were collected by hospital cancer registry from 2020 to 2022. The demographic and clinical features of the patients were abstracted included registration number, age, parity, place of residence, family history, and past medical history. Descriptive statistics in form of percentage with 95% CI was used to explain distribution of cancer cases by study variables. The data was compared using Chi-Square using SPSS Statistics for Windows, Version 26. Results: The results showed that over three years period, 82 confirmed cases of endometrial cancer were registered at Sabratha National Cancer Institute. The average age of cases was 57 years. Analysis of the cases by the age group showed that about 21% of cases were from 46-55years group while over 64% were aged above 50 years. Almost of cases (25%) came from Tripoli while only 6% came from Sabratha which is the place of cancer institute. Analysis of study results by parity showed that both nulliparous women and parous women ( &gt; 6 child) represent almost more than 50% of endometrial cancer cases during study period. Also, analysis of study results by family history of endometrial cancer showed that only 14% of cases had family history of the cancer. Conclusion: It can be concluded that the findings of this 3-year data analysis on endometrial cancer epidemiology provide valuable insights into the trends and patterns of this disease. The study highlights the importance of continued surveillance and research to better understand the risk factors, incidence rates, and outcomes associated with endometrial cancer. This information can help inform public health strategies, early detection efforts, and treatment approaches to improve patient outcomes and reduce the burden of this disease. Further research is needed to explore potential interventions and preventive measures that can address the growing impact of endometrial cancer on global health.

Gap in knowledge of health benefits and risks of combined oral contraceptives among Lebanese women

BackgroundOral Contraceptive Pills (OCPs) are among the most commonly used forms of contraception, but they are associated with several health benefits and risks. This study aims to determine the gap in knowledge of the underlying health benefits and risks of OCPs among Lebanese women and to identify the factors that might influence their beliefs.MethodsA questionnaire was completed by 817 Lebanese women aged 18–64 years old and assessed sociodemographic details, medical information, contraceptive practices, knowledge of underlying health benefits and risks, and information needs related to OCPs.ResultsAmong the total participants, 41.5% of women reported using OCPs at some point in their lives yet 46.6% denied receiving information about their benefits and 48% denied receiving information about their risks. The mean total OCP knowledge score was 5.70 out of 25, the mean OCP risk knowledge score was 4.09 out of 15, and the mean OCP benefit knowledge score was 0.77 out of 6. Sociodemographic factors associated with greater total knowledge, risk knowledge and benefit knowledge included OCP usage, being a student, confidence in one’s knowledge and satisfaction with one’s information. Both the total and risk knowledge scores were found to be higher in women who found that receiving information related to OCPs was important. Finally, participants who lived in central governates had greater total knowledge scores, whereas those with higher levels of education and a family history of endometrial cancer demonstrated better benefit knowledge.ConclusionsThis study highlighted the poor knowledge of health benefits and risks associated with OCP use among Lebanese women and the associated sociodemographic factors that might influence their beliefs.

Risk of estrogen receptor-specific breast cancer by family history of estrogen receptor subtypes and other cancers.

The extent to which the risk of estrogen receptor (ER)-specific breast cancer is associated with ER status of breast cancer and other cancers among first-degree relatives is unclear. This population-based cohort included 464 707 cancer-free women in Stockholm, Sweden, during 1978-2019. For ER-negative and ER-positive breast cancers, we estimated hazard ratios (HRs) associated with ER status of female first-degree relatives with breast cancer and of other cancers in all first-degree relatives. Associations between ER-negative and ER-positive status by family cancer history were estimated using logistic regression in a case-only design. Women with familial ER-positive breast cancer had 1.87 times (95% confidence interval [CI] = 1.77 to 1.97) higher risk of ER-positive subtype, whereas the corresponding hazard ratio for ER-negative was 2.54 (95% CI = 2.08 to 3.10) when having familial ER-negative breast cancer. The risk increased with an increasing number of female first-degree relatives having concordant subtypes and younger age at diagnosis (Ptrend <.001 for both). Nonbreast cancers among first-degree relatives were associated with both ER-positive (HR = 1.14, 95% CI = 1.10 to 1.17) and ER-negative (HR = 1.08, 95% CI = 1.01 to 1.16) breast cancers. Compared with women with ER-positive breast cancer, women with ER-negative breast cancer were more likely to have family history of liver (odds ratio [OR] = 1.33, 95% CI = 1.05 to 1.67), ovary (OR = 1.28, 95% CI = 1.01 to 1.61), and testicle cancer (OR = 1.79, 95% CI = 1.01 to 3.16) but less likely to have family history of endometrial cancer (OR = 0.77, 95% CI = 0.60 to 1.00) and leukemia (OR = 0.72, 95% CI = 0.56 to 0.91). Risk of ER-specific breast cancer differs according to ER status of female first-degree relatives with breast cancer and some other cancers of first-degree relatives. This family history information should be considered in the individual risk prediction for ER subtypes.

Knowledge of endometrial cancer risk factors and symptoms at the Minnesota State Fair (393)

Knowledge of endometrial cancer risk factors and symptoms at the Minnesota State Fair (393)

Contribution of family history of gynecologic cancers to associated risk-factors and screening: Analysis of an Internet-based risk assessment tool.

e13605 Background: Well-established risk-factors exist for gynecologic cancers (GC): estrogen exposure increases risk of endometrial cancer (EC); HPV infection and smoking are associated with cervical cancer (CC); oral contraceptive (OCP) use may be associated with an increased risk of CC but a reduced risk of EC and ovarian cancer (OC). Women with a family history (FH) of cancer are more likely to receive regular CC screening, but the association between FH of GC and other risk factors has not been investigated. Methods: Reduce My Risk is an Internet tool created in 2009 to provide personalized information regarding cancer risk, available at OncoLink.org. Voluntary participants were asked about risk factors and risk-associated behaviors. Differences between female respondents with v. without FH of GC were analyzed using chi-square test. Results: Among 16,878 female respondents, 841 (5.0%) had FH of CC, 345 (2.0%) EC, 1,117 (6.6%) OC, and 92 (0.5%) vulvar/vaginal (VC) cancer. Those with FH of any GC showed no difference in alcohol consumption compared to those without FH. Those with FH of CC, EC, OC, and VC were more likely to be obese (34.1% v. 24.7%; 37.2% v. 24.9%; 31.4% v. 24.7%, 43.7% v. 25%, p &lt; 0.001 for all). Those with FH of CC were more likely to have first sexual intercourse before age 18 (69.2% v. 57.8%, p &lt; 0.001) and to have &gt; 10 sexual partners (24.0% v. 16.7%, p &lt; 0.001). This group was also more likely to be current smokers (19.3% v. 11.7%, p &lt; 0.001), and to smoke &gt; 1 pack/day (6.5% v. 2.8%, p &lt; 0.001). They were more likely to receive regular CC screening (91.2% v. 86.8%, p = 0.09), though the difference was not statistically significant. Women &lt; 35 y with a FH of CC showed no differences in HPV vaccination rate (37.0% v. 39.3%, p = 0.29). Those with FH of EC were more likely to have menarche before age 12 (39.3% v. 32.0%, p = 0.005), and to have taken post-menopausal HRT for ≥2 y (77.6% vs. 66.8%, p &lt; 0.001). Those with FH of EC, and OC were more likely to have taken OCPs (77.6% v. 66.8%; 71.9% v. 66.7%, p &lt; 0.001 for both). Conclusions: Many with a FH of GC have increased likelihood of both modifiable and non-modifiable risk factors that are associated with the development of cancer. FH of CC did not increase likelihood of regular screening or HPV vaccination, but was associated with smoking, early intercourse, and multiple sexual partners. Future work should explore targeted intervention for those with FH of GC as a teachable opportunity for the benefits of weight reduction, smoking cessation, pap screening, and HPV vaccination.

Abdominal skin metastasis in endometrial cancer

Objectives: Surgical wound metastases in stage 1 endometrial cancer are possible, with a variety of different pathophysiological possibilities. Comprehensive management is needed to keep the patient on the possibility of a good prognosis.Cases Report: During January 2015 – January 2018 at dr. Soetomo Hospital, there were 2 cases of metastatic endometrial cancer in the laparotomy wounds by which the condition is very rare. Case 1, The patient was diagnosed with endometrial carcinoma following the results of curettage. Anatomical pathology examination was done and obtained grade 2 endometrioid adenocarcinoma. In Case 2, the patient underwent Total Abdominal Hysterectomy and Bilateral Salpingo-Oophorectomy in 2013 at Mojokerto General Hospital, indicating Uterine Fibroids and Ovarian Cysts. The results of anatomical pathology examination were unknown. On April 2017, the patient complained abdominal swelling since 3 months ago.Conclusion: In January 2015 - January 2018, 2 cases of metastatic endometrial cancer was found in a former laparotomy operation where this condition is very rare in endometrial cancer cases with low grade ,so that follow-up, monitoring and more vigilance are required in patients with low-grade endometrial Ca who have finished undergoing a surgery and chemotherapy. Rapture or mass resection, followed by external radiation, may be performed in patients with recurrence in the laparotomy wound area or in patients with high risk factors for endometrial cancer such as a history of estrogen use, tamoxifen, nullipara, obesity, diabetes mellitus, and family history of endometrial cancer. Currently, there is no fixed procedure (guideline) in RS. Dr. Soetomo to overcome recurrences especially in the scars of cancer surgery.

Clinicopathologic features of endometrial cancer in Chinese patients younger than 50 years with a family history of cancer.

Genetic factors play an important role in shaping the biologic characteristics of malignant tumors, especially in young patients. We aimed to determine the clinicopathologic features of endometrial cancer (EC) in patients younger than 50 years with a family history of cancer.Overall, 229 patients with EC, including 40 with a positive family history of cancer (PFH) and 189 with a negative family history of cancer (NFH), were enrolled in this case–control study. The family history of cancer in a 2-generation pedigree was recorded for the PFH group. Clinicopathologic features such as menarche age, body mass index, personal cancer history, grade, and histologic type were compared between the 2 groups. Mismatch repair (MMR) proteins including MLH1, PMS2, MSH2, and MSH6 were assessed by immunohistochemistry (IHC) in surgical samples. Univariate (Pearson Chi-squared test, Fisher exact test, T test, Wilcoxon rank sum test, logistic regression) statistics and stepwise multivariate logistic regression were used to identify factors associated with PFH in the analysis.Among young patients with EC, the PFH group had younger age-of-onset age of endometrial cancer (≤40 years) (odds ratio [OR] = 2.21, 95% confidence interval [95% CI]: 1.01–4.82) than the NFH group. The proportion of overweight/obese patients was high in both the NFH (58.7%) and PFH (80%) groups. Colorectal, lung, endometrial, breast, and hepatocellular carcinoma accounted for 58.6% of all cancer types among 1st- and 2nd-degree relatives. Additionally, 19.2% of patients displayed deficiency in at least 1 MMR protein, with a significantly higher proportion of MMR protein deficiency in the PFH group than in the NFH group (adjusted OR = 4.81, 95% CI: 2.14–8.83).Clinicopathologic features differ for young patients with EC with and without a family history of cancer. Surveillance of age-of-onset and family history of endometrial cancer, reduction of barriers to healthy lifestyles, and development of risk-appropriate Lynch syndrome screening tools, such as IHC, are needed for these women in Shanghai and other developing cities in China.

Family history and risk of endometrial cancer: a systematic review and meta-analysis.

To obtain precise estimates of endometrial cancer risk associated with a family history of endometrial cancer or cancers at other sites. For the systematic review, we used PubMed to search for all relevant studies on family history and endometrial cancer that were published before December 2013. Medical Subject Heading terms "endometrial neoplasm" and "uterine neoplasm" were used in combination with one of the key phrases "family history," "first-degree," "familial risk," "aggregation," or "relatedness." Studies were included if they were case-control or cohort studies that investigated the association between a family history of cancer specified to site and endometrial cancer. Studies were excluded if they were review or editorial articles or not translated into English or did not define family history clearly or used spouses as control participants. We included 16 studies containing 3,871 women as cases and 49,475 women as controls from 10 case-control studies and 33,510 women as cases from six cohort studies. We conducted meta-analyses to estimate the pooled relative risk (95% confidence interval [CI]) of endometrial cancer associated with a first-degree family history of endometrial, colorectal, breast, ovarian, and cervical cancer to be: 1.82 (1.65-1.98), 1.17 (1.03-1.31), 0.96 (0.88-1.04), 1.13 (0.85-1.41), and 1.19 (0.83-1.55), respectively. We estimated cumulative risk of endometrial cancer to age 70 years to be 3.1% (95% CI 2.8-3.4) for women with a first-degree relative with endometrial cancer and the population-attributable risk to be 3.5% (95% CI 2.8-4.2). Women with a first-degree family history of endometrial cancer or colorectal cancer have a higher risk of developing endometrial cancer than those without a family history. This study is likely to be of clinical relevance to inform women of their risk of endometrial cancer.

Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

ObjectiveTo determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer. MethodsWe retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan–Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer. ResultsA total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70years was estimated to be 0.94% (95% CI 0.83–1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75–4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63–5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age <50years (HR 1.48, 95% CI 1.15–1.91). ConclusionAn increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.

Genome-wide association study of endometrial cancer in E2C2

Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-013-1369-1) contains supplementary material, which is available to authorized users.

An alternative approach to identify women at risk for colorectal cancer.

1513 Background: Hereditary colorectal cancer (CRC) is preventable; however, identification of individuals at sufficiently high risk to warrant heightened surveillance is difficult. Lynch Syndrome (LS) is an inherited cancer syndrome due to germline mutation in a DNA mismatch repair gene. For women with LS, the lifetime risk of endometrial cancer (EC) is 64% and CRC is 54%. Fifty percent of women with LS will present with EC or ovarian cancer prior to CRC. Therefore, women with LS associated EC represent an ideal group for CRC prevention. The optimal method to identify women with LS associated EC is not known. The purpose of this study was to determine the utility of Amsterdam II and Society of Gynecologic Oncology (SGO) Criteria (modified Bethesda criteria that use EC as the sentinel cancer) in identifying women with LS associated EC. Our ultimate goal is to identify women at increased risk of CRC. Methods: Immunohistochemistry (IHC) for DNA mismatch repair proteins and MLH1 methylation analyses were used to identify LS associated EC among 388 women. EC was designated as LS if there was loss of mismatch repair protein expression. Absence of MLH1 methylation was required to confirm LS in tumors with MLH1 protein loss. Results: Fifty-nine (15.2%) of the EC patients tested had LS. These patients are summarized in the table. Conclusions: Clinical criteria to detect LS identify 17/59 (29%) - 44/59 (74%) of women who present with EC first. EC with MSH2 loss is most likely to occur in younger women and women with positive family history of EC and CRC, features classically associated with LS. In general, the MSH6 mutation is associated with older age at diagnosis and fewer familial CRCs, however, we found a large number of MLH1 (50%) and PMS2 (86%) cases diagnosed at greater than 50 years with no family history of CRC. Our data suggest that classic clinical screening criteria are inadequate to detect patients with LS who present with EC, potentially missing up to 25% of these patients. [Table: see text]

Abstract B29: Screening and communication with physicians for women with Lynch syndrome: Findings from a qualitative study

Abstract Background: Lynch syndrome, which is also known as hereditary non-polyposis colon cancer (HNPCC), is an autosomal dominant hereditary cancer syndrome that confers women with a 40–60% lifetime risk of endometrial cancer (EC) and a 12% lifetime risk of ovarian cancer (OC). Consensus statements recommend annual EC and OC screening for women with Lynch syndrome, initiated at age 30–35 or 10 years younger than the earliest known case in the family. This study evaluated the prevalence of EC and OC screening behaviors among women at risk for Lynch syndrome, and communication with their physicians about EC and OC risk and screening needs. Methods: Women age &amp;gt; 25 years who were at risk for Lynch syndrome-related cancers, and who had not had both a hysterectomy and oophorectomy, completed a semi-structured interview either in person or over the phone. The domains covered included demographics and medical history, knowledge of screening recommendations, screening for Lynch-syndrome associated gynecological cancers, and physician-patient communication. SPSS and NVivo™ were used for data analysis. Results: Fifty-two women (mean=40.6 years old) participated. They were mostly white, married, well-educated, and had children. Approximately 70% were Lynch-syndrome mutation carriers while the remaining 30% met the Amsterdam II criteria. Approximately 70% reported a family history of EC or OC. All but five had received genetic counseling regarding their risk for Lynch syndrome. Half of the participants correctly answered questions about the appropriate age to begin screening, while approximately 75% correctly assessed the recommended screening frequency. Approximately half of the women reported never having had asymptomatic gynecological screening. Between 15 and 38% were currently adherent to screening recommendations because they received screening as part of a research study. Women who were seeing non-oncology gynecologists were not offered appropriate EC or OC screening, although they uniformly expressed a high level of trust and value in the care provided by these physicians and believed that their physicians were doing the best job possible to manage their health needs. Approximately 33% of the women report that cost and lack of insurance might prevent their screening adherence in the future. Conclusions: Lynch syndrome-affected families and their primary care physicians may lack accurate knowledge of EC and OC risks. Women who are at risk for Lynch syndrome may not receive appropriate EC or OC screening from their community physicians, and new prevention-communication strategies may be needed. Participation in research studies may improve adherence to screening for gynecologic cancers in Lynch syndrome. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B29.

Family history of cancer and the risk of endometrial cancer

To investigate the relationship between family history of cancer in first-degree relatives and the risk of endometrial cancer, we carried out a large multicentre case-control study in Italy between 1992 and 2006, including 454 endometrial cancer cases and 908 controls admitted in hospital for acute, non-neoplastic diseases. Conditional logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CI). Relative to women with no family history of uterine cancer, the ORs were 2.1 (95% CI: 0.7-6.4) for those reporting a family history of endometrial cancer and 1.8 (95% CI: 1.0-3.2) for a family history of any uterine cancer. A family history of intestinal cancer was directly associated with endometrial cancer risk (OR=1.6; 95% CI: 1.0-2.7). Direct associations were found for a few other cancer sites. In conclusion, a family history of endometrial, uterine or intestinal cancer in first-degree relatives is associated with an increased risk of endometrial cancer.

Infant feeding and the incidence of endometrial cancer.

Biological mechanisms could support both an inverse and a direct association between exposure to breast milk in infancy and the risk of cancer. Having been breast-fed has been investigated in relation to the risk of breast and other cancer sites, and conflicting results have been reported. The association between infant feeding and the risk of endometrial cancer has not been explored. From 1976 to 2004, we followed 74,757 cancer-free participants in the Nurses' Health Study who had not undergone hysterectomy. Information on infant feeding was self-reported by study participants. A total of 708 incident cases of endometrial cancer were diagnosed during follow-up. After adjusting for age, family history of endometrial cancer, birth weight, premature birth, and birth order, the incidence of endometrial cancer was not associated with ever having been breast-fed (hazards ratio, 0.94; 95% confidence interval, 0.79-1.11) or duration of having been breast-fed [hazards ratio (95% confidence interval): 1.11 (0.80-1.54), 0.84 (0.62-1.13), 1.02 (0.79-1.31), respectively, for < or =3, 4-8, and > or =9 months of having been breastfed; P for trend = 0.88]. There was no significant effect modification by menopausal status, anthropometric factors (somatotype at age 5 or 10 years, body mass index at age 18 years, or current body mass index), or by other early-life exposures (birth weight, premature birth or exposure to parental smoking in childhood). Additional adjustment for adulthood risk factors of endometrial cancer did not materially change the results. Having been breast-fed was not associated with the incidence of endometrial cancer in this cohort, but statistical power for analyses restricted to premenopausal women was limited.

Effect of ATM, CHEK2 and ERBB2 TAGSNPs and haplotypes on endometrial cancer risk

Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in the ATM, CHEK2 and ERBB2 genes in relation to endometrial cancer risk overall, restricted to tumours of certain characteristics or stratified by various endometrial cancer risk factors. We genotyped a large number of single-nucleotide polymorphisms (SNPs) in the genes and selected seven haplotype-tagging SNPs (tagSNPs) in ATM, six tagSNPs in CHEK2 and seven tagSNPs in ERBB2 that could predict common variants and haplotypes (frequency > or =0.03) in each gene with R(2) > or = 0.8. We included the tagSNPs or their haplotypes as explanatory variables in unconditional logistic regression models adjusted for age. Our results indicated an increased risk of developing endometroid endometrial cancer for homozygous carriers of the rare allele (AA) of a tagSNP (rs4987886) in CHEK2 (P = 0.005) when contrasted with GG carriers. We also found a decreased endometrial cancer risk among non-smoking carriers of a haplotype in ATM (P = 0.0007) and among carriers of a haplotype in CHEK2, who had experienced menopause below 49 years of age (P = 0.0009) compared with non-carriers of these haplotypes. We found no effect of genetic variation in ERBB2 on endometrial cancer risk. In conclusion, it is possible that common variants in the ATM and CHEK2 genes, in interaction with oestrogen-related exposures, are involved in endometrial cancer aetiology.

Lymphotoxin-α polymorphisms and the risk of endometrial cancer in Japanese subjects

To test the association of endometrial cancer with the lymphotoxin-alpha (LTalpha) C804A and A252G polymorphisms, a hospital-based incident case-control study was performed in Japanese subjects. The cases comprised 110 endometrial cancer patients, and the controls were 220 age-matched cancer-free females. The LTalpha C804A and A252G polymorphisms were in complete linkage disequilibrium. We performed conditional logistic regression analysis adjusted for age, which revealed that the LTalpha 252AG and 804CA variant genotypes were associated with a significantly reduced risk of endometrial cancer (OR=0.51, 95% CI=0.31-0.86, P=0.011). Being homozygous of the LTalpha 252G and 804A alleles was not associated with the risk of endometrial cancer. However, the presence of at least one variant LTalpha allele was associated with a significantly lower risk of endometrial cancer (OR=0.54, 95% CI=0.33-0.87, P=0.012). After adjusting for potential confounders (body mass index, age at menarche, parity, hypertension, diabetes mellitus, family history of endometrial cancer, hormone replacement therapy, smoking status, and alcohol consumption), the risk of endometrial cancer was significantly lower both in carriers of one variant allele and in carriers of either one or two of the variant alleles (OR=0.47, 95% CI=0.26-0.85, P=0.017; OR=0.50, 95% CI=0.28-0.89, P=0.019; respectively). The results suggest that these LTalpha polymorphisms play an important role in the tumorigenesis of endometrial cancer.

An overview of uterine cancer and its management

Endometrial cancer is increasingly common in affluent Western countries, largely owing to the growing obesity of those populations. There are two recognized types of endometrial cancer: Type I is more common and is associated with obese postmenopausal women and comprises approximately 80% of all endometrial cancers; Type II describes a woman who is often younger and thinner with a more aggressive histologic type that is nonestrogen dependent, of either serous or clear cell histology, and consists of a more aggressive clinical course and results in poorer prognosis. As the majority of patients with endometrial cancer present with symptoms and have early disease, screening is unlikely to be cost effective or reduce the mortality rate. However, surveillance of high-risk populations is a different proposition. Patients who may benefit from routine surveillance include those with a family history of endometrial cancer, a history of hormone replacement therapy with less than 12–14 days of progestogens, long-term use of tamoxifen, hereditary nonpolyposis colorectal cancer family syndrome, Cowden’s syndrome, Peutz-Jeghers syndrome, a history of breast cancer and obesity. Most patients with endometrial cancer are offered surgery as first-line therapy. The standard surgical procedure should be an extrafascial total hysterectomy with bilateral salpingo-oophorectomy. Adnexal removal is also recommended, even if the adnexa appear normal, as they may contain micrometastases. The safety of a laparoscopic approach in the surgical management of uterine cancer has not yet been demonstrated in prospective randomized trials, therefore, the field awaits the Gynaecologic Oncology Group’s prospective Lap-2 study. While post-treatment follow-up guidelines vary between institutions and countries, in general, patients at high risk of recurrence are followed closely every 3–4 months for the first year or two, then every 6 months to complete 5 years of follow-up.

Ovarian Conservation at the Time of Hysterectomy for Benign Disease

To the Editor: Prophylactic oophorectomy during hysterectomy for benign disease has recently been challenged1 using a Markov Decision Analysis. While this is appropriate from a mathematical perspective, as the conclusions may change future clinical practice, it is urgent to clarify some of the weaknesses of this approach. First, any decision analysis only incorporates the risks selected, not all risks. For example, gallbladder disease, which is associated with higher estrogen levels, is not considered. While one may suspect that the mortality associated with increased gallbladder surgery is minor, it is an illustration of the kind of risks overlooked. Second, the study is entirely dependent on the “risk estimates” incorporated. Figure 1 is entirely explicable by the difference in coronary heart disease risk assumed. Below age 55 the coronary heart disease relative risk (RR) is 2. This is decreased by 6% annually, but there are no data for post-65 years old, and so a RR 1 was assumed. Unfortunately, estrogen’s effect on coronary heart disease is highly debated and the Women’s Health Initiative (WHI)2 indicated that hysterectomy patients, regardless of oophorectomy status, had a significant increase in total mortality and fatal and nonfatal cardiovascular disease. This observation is ignored and would essentially remove the difference in Figure 1. Comparing Table 2 of the original paper (which should, but does not, include 95% confidence intervals) with Figure 1 shows that oophorectomy with estrogen therapy is not statistically significantly different from ovarian preservation. Other risks are selected by author consensus when studies conflict. Finally, the assertion by Parker et al that the difference in surgical mortality is insignificant disregards the probability (3–4%) of the need to reoperate for ovarian pathology. The writer believes the current algorithm is too crude as a basis for clinical judgment. A nulliparous smoker with a family history of endometrial cancer is at a far higher risk of ovarian cancer than one without these factors. The current paper would have us treat them the same. Clearly this is inappropriate.

Clinical and molecular characteristics of hereditary non‐polyposis colorectal cancer families in Southeast Asia

Lee S-C, Guo J-Y, Lim R, Soo R, Koay E, Salto-Tellez M, Leong A, Goh B-C. Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia. Hereditary non-polyposis colorectal cancer (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form of hereditary colorectal cancer (CRC), but data in Asians are sparse. We sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients diagnosed below age 40, and/or with multiple primary cancers or familial cancer clustering suggestive of HNPCC, and correlated deleterious mutations with clinical and tumour features. Forty-six Chinese, Malay and Indian kindreds participated. Of the 153 cancers reported in the 46 kindreds, stomach (14%) and urogenital cancers (13%) were the most common extracolonic cancers, whereas endometrial cancer comprised only 7%. Eleven different MLH1 and 12 MSH2 mutations were identified, including nine novel and four recurring mutations in the Chinese. One Indian was a compound heterozygote for an MLH1 and MSH2 mutation. The MLH1/MSH2 mutation data in the Malays and the Indians represents the first in these ethnic groups. Factors strongly associated with deleterious mutations were the Amsterdam criteria, family history of stomach or multiple primary cancers, and MSI-high tumours, whereas family history of endometrial cancer and young cancer age alone correlated poorly. Distinct clinical and molecular characteristics were identified among Asian HNPCC kindreds and may have important clinical implications.