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The environments of nursing home staff and residents have dramatically changed since the onset of the COVID-19 pandemic, with greater demand for infection control. This study aimed to clarify the changes and regional differences in the surrounding environment of nursing home residents as well as the working environment of staff, including oral health care, after the spread of SARS-CoV-2. A self-administered questionnaire survey was sent to nursing staff at about 40 nursing homes in different areas of Japan in September and October 2021. The questionnaire consisted of items centered around: (1) the surrounding environment of nursing home residents, (2) awareness and attitudes towards daily work among staff, and (3) attitudes to and procedures for oral health care among staff. A total of 929 respondents included 618 (66.5%) nursing care workers and 134 (14.4%) nurses. Regarding changes in resident daily life, 60% of staff perceived decreases in psychosocial and physical function after the start of the pandemic due to limited family communication and recreational activities, especially in urban areas. Concerning infection control, most respondents adopted routines of disinfecting hands before and after their duties. Oral health care was part of the regular duties of over 80% of respondents. Many participants answered that the frequency and time of oral health care only slightly changed after the onset of COVID-19, but many also reported disinfecting hands both before and after oral health care, particularly in rural areas. Our findings suggested that the COVID-19 pandemic decreased the daily living activities of residents, leading to psychosocial and physical decline, especially in urban areas. The results also indicated that the spread of SARS-CoV-2 triggered improvements in the awareness and attitudes towards infection control in daily work, including oral health care, among nursing care staff, notably in rural areas. Such an effect may contribute to a more positive perception of oral health care infection measures after the pandemic. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the clinical background and treatment outcomes of risk-reducing salpingo-oophorectomy (RRSO) in Japan for women with hereditary breast and ovarian cancer (HBOC). Methods: In the present retrospective observational study, we examined the Japanese HBOC Consortium's (JHC) database. This database contains 11,711 probands who received BRCA genetic testing, or their relatives, with any cancer in 2433 pedigrees. This study was supported by the registration committee of the JHC. Results: We analyzed 488 individuals diagnosed with HBOC, of which 153 (31.4%) underwent RRSO. Of the latter patients, 88 carried BRCA1 mutation (B1); 62 carried BRCA2 mutation (B2); and 3 carried both mutations. During a mean follow-up period of 2.6 years (range 0–12.6), one patient developed a primary peritoneal cancer (PPC). Clinical background comparison for individuals who underwent RRSO vs. those > 45 years of age who did not undergo RRSO revealed that significant factors were represented by B1 (p < 0.0001); child bearing (p < 0.00001); and breast cancer history (p < 0.01). However, family history of ovarian cancer and menopause status were not significantly different. Conclusion: Over 30% HBOC's in Japan underwent RRSO. In Japan, individuals with breast cancer history and B1 generally underwent RRSO, whereas those who did not bear a child mostly avoided RRSO. [ABSTRACT FROM AUTHOR]

The influence of life stage on psychosocial adjustment and on factors related to this adjustment were examined in post-operative colorectal cancer patients without stoma. PAIS-SR (Psychosocial Adjustment to Illness Scale-Self-Report) was used to assess psychosocial adjustment, and patients were divided into two groups; a senior group (age > 65 years, n = 34) and a non-senior group (age < 65 years, n = 59) based on cultural features in Japan. Results were compared between two groups for each of the following PALS domains: ‘vocational environment,’ ‘domestic environment,’ ‘sexual relationship,’ ‘extended family environment,’ ‘social environment,’ and ‘psychological distress.’ Psychosocial adjustment was found to differ by life stage only for ‘psychological distress’ (non-senior vs. senior: 48.6 ± 9.4 vs. 44.7 ± 7.7, p < .05). However, analysis of background factors related to psychosocial adjustment revealed distinct patterns in each life stage. This study suggests that life stage should he considered when attempts are made to improve the psychosocial adjustment among cancer patients. [ABSTRACT FROM AUTHOR]

Provides a historical perspective on familial cancer in Japan. Results and vision of the Polyposis Center Project; Prelude to cancer molecular genetics and medicine; Comments on the role of familial cancer approach in genomic medicine.

The Japanese Breast Cancer Society Clinical Practice Guidelines for Epidemiology and Prevention of Breast Cancer, 2022 Edition., (© 2023. The Author(s).)

Alcohol consumption is internationally recognized as one of the compelling risk factors for breast cancer, but it does not necessarily correlate with the prognosis of breast cancer patients. Alcohol consumption in breast cancer patients was addressed in the 2022 Breast Cancer Clinical Practice Guidelines. A systematic review and meta-analysis of epidemiological studies on alcohol consumption and breast cancer recurrence, breast cancer-related mortality, all-cause mortality, and cardiovascular disease mortality in breast cancer patients was performed. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting cohort or case-control studies published until March 2021. A total of 33 studies (32 cohort studies and 1 case-control study) met the eligibility criteria; 4638 cases of recurrence, 12,209 cases of breast cancer-specific mortality, and 21,945 cases of all-cause mortality were observed. With regard to breast cancer recurrence, 7 studies assessed pre-diagnosis alcohol consumption (relative risk (RR) 1.02, 95% confidence interval (95% CI) 0.77-1.37, p = 0.88) and 3 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.85-1.10, p = 0.57), and no significant increase or decrease in risk was observed. With regard to breast cancer-related mortality, 19 studies assessed pre-diagnosis alcohol consumption (RR 1.02, 95% CI 0.93-1.11, p = 0.69), 9 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.77-1.19, p = 0.70), and no significant increase or decrease in risk was observed. With regard to all-cause mortality, 18 studies assessed pre-diagnosis alcohol consumption (RR 0.90, 95% CI 0.82-0.99, p = 0.02), 8 studies assessed post-diagnosis alcohol consumption (RR 0.88, 95% CI 0.74-1.02, p = 0.08), and pre-diagnosis alcohol consumption was associated with a significantly decreased risk. With regard to cardiovascular disease mortality and alcohol consumption, 2 studies assessed it, and the RRwas 0.47 (95% CI 0.28-0.79, p = 0.005), showing that alcohol consumption was associated with a significantly decreased risk. The limitations of this study are that drinking status was mainly based on a questionnaire survey, which is somewhat inaccurate and has many confounding factors, and the cut-off value for the maximum alcohol intake in many studies was low, and it is possible that the actual intake was only an appropriate amount. In many countries, a standard drinking amount is set, and wise decisions are required., (© 2023. The Author(s).)

Background: Risk-reducing mastectomy is one option for women with hereditary breast and ovarian cancer to reduce the risk of breast cancer., Patients and Methods: We analyzed data of the Japanese Organization of Hereditary Breast and Ovarian Cancer on women who were diagnosed as hereditary breast and ovarian cancer by BRCA germline genetic testing between 2010 and 2019 to reveal the rate and likelihood of risk-reducing mastectomy., Results: There were 412 women with BRCA1, 271 with BRCA2 and 4 with both female pathogenic variants. Ninety (13.1%) received risk-reducing mastectomy. The rates of risk-reducing mastectomy were statistically significantly higher in women with BRCA1 pathogenic variants than BRCA2, in women who had breast cancer than those who did not, in women with a breast cancer family history than in those without, in mothers than in those without children, in women who were receiving surveillance with MRI than those who were not and in women who received risk-reducing salpingo-oophorectomy than in those who did not on univariate analyses. The ages when they received the genetic testing were statistically significantly younger in the women receiving risk-reducing mastectomy than those who did not receive it. The women with BRCA1 pathogenic variants, personal history of breast cancer, mothers, those receiving MRI surveillance and younger women were independently significantly more likely to receive risk-reducing mastectomy based on multivariate analysis., Conclusions: The rate of risk-reducing mastectomy was not high in Japan; however, risk-reducing surgery was approved by the Japanese National Medical Insurance for hereditary breast and ovarian cancer patients with breast and/or ovarian cancer in 2020, so this rate will increase., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers., Methods: We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (g BRCA1 m), germline BRCA2 mutation (g BRCA2 m) and germline BRCA wild-type (g BRCA wt) were found in 185, 42 and 241 OC patients, respectively., Results: The average age at diagnosis of OC in g BRCA1 m and g BRCA2 m was 51.3 and 58.3 years, respectively, and the difference from g BRCA wt (53.8 years) was significant. The g BRCA2 m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1 , and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCA2 . The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA2 carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40., Conclusion: There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed., Competing Interests: Masayuki Sekine received lecture fees from AstraZeneca. Takayuki Enomoto received lecture fees from AstraZeneca and Chugai Pharmaceutical. Seigo Nakamura received an honoraria for a seminar presentation from AstraZeneca and KONICA MINOLTA. The other authors declare no conflicts of interest., (Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

We previously reported that L63X and Q934X are BRCA1 common founder variants in Japan. So far, there have been no reports of a correlation between such BRCA common variants and the risk of BRCA-related cancers. In this analysis, we investigated the correlation between the risk of ovarian cancer (OC) and BRCA recurrent pathogenic variants. We examined the database of the Japanese organization of hereditary breast and ovarian cancer. The database contained 3517 probands who underwent BRCA genetic testing. Among them, 11.1% (392/3517) had germline BRCA1 pathogenic variant, and 8.3% (293/3517) had BRCA2 pathogenic variant. We calculated the OC prevalence, breast cancer (BC) prevalence, and the ratio of OC to BC within second-degree relatives. The ratio of OC to BC in Q934X family members was significantly higher than that in the overall BRCA1 family members (0.80 vs.0.52: p = 0.038), and the ratio in STOP799 was 0.42, which was relatively lower than the overall BRCA1 value. Both Q934X and STOP799 are located in the ovarian cancer cluster region (OCCR), however there seems to be a difference in the risk of OC. R2318X family members had a significant higher ratio of OC to BC at 0.32 than the overall BRCA2 value of 0.13 (p = 0.012). R2318X is known to be located in the OCCR. This is the first report to investigate the correlation between BRCA recurrent variants and the risk of OC in Japan. The family members of probands with Q934X or R2318X have a higher risk of OC than that with other BRCA variants., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

This study aimed to clarify the breast cancer prognosis in Japanese patients with BRCA1/2 pathogenic variant. We analyzed 2235 women with breast cancer who underwent BRCA1/2 genetic testing between 1996 and 2018 using data from the Japanese hereditary breast and ovarian cancer syndrome registry. The cumulative risk for contralateral and ipsilateral breast cancers and time to death since the first breast cancer were stratified based on the BRCA1/2 variant status. The median follow-up was 3.0 years (0.1-34.1 years) after the first breast cancer. The annual average risks of contralateral breast cancer in BRCA1 and BRCA2 and non-BRCA1/2 pathogenic variant carriers were 4.0%, 2.9%, and 1.9%, respectively (P = 0.001). The annual average risks of ipsilateral breast cancer in the three groups were 2.7%, 1.4%, and 1.1%, respectively (P = 0.06). BRCA1 pathogenic variant carriers had significantly higher risks of contralateral (hazard ratio 1.91, P < 0.001) and ipsilateral (hazard ratio 2.00, P = 0.02) breast cancers than non-BRCA1/2 pathogenic variant carriers. The time to death by the BRCA1/2 variant status was not significantly difference (P = 0.28). The prognosis of breast cancer patients who received standard treatment was comparable regardless of the BRCA1/2 variant status.

BRCA1/2 pathogenic variant prevalence in Japanese breast cancer is unclear. Here, we analyzed BRCA1/2 pathogenic variant prevalence with a particular focus on age factors, using the Japanese HBOC consortium database. All registered subjects were Japanese individuals who underwent BRCA1/2 genetic testing from January 1996 to July 2017 according to the Japanese HBOC consortium database. Cases were extracted and analyzed for each evaluation item. Overall BRCA1 and BRCA2 pathogenic variant prevalence was 11.2% and 9.0% in the cohort of 2366 proband patients, respectively. The age at onset of breast cancer for patients with BRCA1/2 pathogenic variants was significantly lower than that for patients without a BRCA1/2 pathogenic variant. In both BRCA1/2 patients, ages at onset were not statistically significantly different between two subtype groups (ER-positive vs. TNBC). We analyzed the BRCA1/2 pathogenic variant prevalence among age groups in patients with no family history of breast or ovarian cancer. In the TNBC group, the rate of genetic variants was more frequent among younger patients. Our results demonstrated that early breast cancer onset is associated with a BRCA1/2 pathogenic variant in the Japanese population. Younger TNBC patients were more likely to have a BRCA1/2 pathogenic variant irrespective of a family history of breast or ovarian cancer.

Background: We studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear., Patients and Methods: The study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium., Results: Our study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05)., Conclusions: Patients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis., Methods: We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing., Results: We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA- (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA- (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T > A and c.2800C > T., Conclusions: This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose: Prophylactic surgery is a preemptive strategy for hereditary breast and ovarian cancer (HBOC). Prophylactic mastectomy (PM) reduces breast cancer risk by > 90%. The aim of our study is to analyze the information of the Japanese pedigrees and to utilize the results for clinical practice., Methods: We statistically analyzed records of HBOC registrees who had undergone BRCA1/2 genetic testing at seven medical institutions up until 2016. In the cases of PM, we examined breasts with the use of mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI) before surgery. After PM, the specimens were divided about 1 cm serially and examined in their entirety., Results: Of 1527 registrees who underwent BRCA testing, 1125 (73.7%) were negative for BRCA1/2 mutation, 297 (19.5%) were positive for BRCA1/2 mutation (BRCA1/2 MUT+ ), and 105 (6.9%) had uncertain results. To decide whether to undergo total mastectomy vs. breast-conserving surgery (BCS), 370 registrees underwent presurgical genetic testing. During the follow-up period, four new-onset breast cancers were found among the 55 non-affected BRCA carriers. Among the 73 BRCA1/2 MUT+ carriers who underwent BCS, 3 were found to have ipsilateral breast cancer. Of 189 BRCA1/2 MUT+ carriers with unilateral breast cancer, 8 were found to have contralateral breast cancer. Of 53 PM specimens, 6 (11.3%) were found to have occult breast cancer despite using MMG, US, and MRI., Conclusions: Our report showed a relatively higher incidence rate of occult cancer at 11.3% in PM specimens despite thorough pre-operative radiological evaluations, which included a breast MRI. Considering the occult cancer rates and the various pathological methods of our study and published studies, we propose the necessity of a histopathological protocol.

We conducted this study to establish whether drinking alcohol alters the risk of early-onset colorectal cancer (CRC) in Japanese patients with Lynch syndrome (LS). The subjects were 66 LS patients with pathogenic mutation of mismatch repair genes (MLH1, MSH2, and MSH6) from the nationwide Japanese retrospective multicenter study. Cox proportional hazards modeling was used to investigate the factors correlating with early-onset CRC diagnosis, using clinical data such as gender, tobacco use, alcohol consumption, body mass index, gene mutation (MLH1, MSH2 vs MSH6), and family cancer history. Alcohol was significantly correlated with an increased risk of early-onset CRC [HR 2.44, 95% CI 1.13-5.16 (p = 0.02)], but tobacco use was not [HR 0.8, 95%CI 0.38-1.62 (p = 0.53)]. These findings suggest that alcohol consumption is correlated with an earlier onset of CRC in Japanese patients with LS.

Objectives: To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics., Methods: A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined., Results: Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria., Conclusions: This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers., (© 2017 The Japanese Urological Association.)

Objective: The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients., Methods: We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X., Results: We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome., Conclusion: A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The recognition of hereditary breast and ovarian cancer (HBOC) is gradually spreading in Japan after a famous American actress made it public that she underwent risk-reducing mastectomy (RRM) based on mutation of BRCA1. HBOC is a cancer susceptibility syndrome involving breast, ovarian, or prostate cancers due to germline mutation of BRCA1 or BRCA2. Although the frequency is low, genomic rearrangement is also found in Japan; therefore, in addition to PCR-direct sequencing, multiplex ligation-dependent probe amplification (MLPA) should be performed in genetic testing for HBOC. Recently, candidate genes other than BRCA1/2, such as RAD51C, PALB2, and BRIP1, have been identified for hereditary breast cancers. Variants of uncertain significance are seen in approximately 4-6% of all genetic testing reports for BRCA1/2. ACMG recommends the use of the term"variant"in addition to a modifier such as pathogenic, benign, and so on, instead of terms such as mutation or polymorphism. The incidence of ovarian cancer is not increased in women from breast cancer-only families that test negative for BRCA1/2 mutations. Therefore, intensive gynecological surveillance may not be needed for these clients. Basic data such as penetrance and cumulative risks of HBOC in Japanese populations are insufficient for risk assessment in genetic counseling. The Japanese HBOC consortium was established, and as one of the activities of the consortium, the registration project will start to provide essential genetic information in clinical practice. In Japan risk-reducing surgeries are, albeit gradually, increasingly being performed to potentially protect mutation carriers against HBOC. Risk-reducing salpingo-oophorectomy (RRSO) is effective in the reduction of the incidence of breast cancer, as well as of ovarian cancer. Furthermore, RRSO is associated with improved overall survival in BRCA1/2 mutation carriers. RRM also reduces the risk of breast cancer by more than 90%, but the survival benefit remains unknown. Recently, contralateral RRM has shown improved overall survival in a prospective analysis. Pathological examination of resected surgical specimens from RRSO revealed that some serous ovarian carcinomas originated from fimbriae of the uterine tube, showing focal p53 overexpression (p53 signature) in the tubal epithelium. Therefore, initial bilateral salpingectomy followed by a delayed oophorectomy may be a proposed alternative to RRSO, but there is no prospective evidence on the efficacy of bilateral salpingectomy.

Lynch syndrome (HNPCC) is an autosomal dominant hereditary cancer syndrome, and members of affected families are at-risk for developing colorectal and other associated tumors. Such individuals should disseminate familial genetic information, so they can seek specific medical assessment or genetic testing to reduce mortality and morbidity rates by early detection. Since published results have been encouraging, we explored which factors influence the likelihood of good communication within families regarding medical assessment. We studied 40 individuals from 33 families who satisfied the Japanese clinical criteria for Lynch syndrome and their relatives at our hospital. We determined the status of relatives of the 40 individuals after genetic counseling and testing using questionnaires and semi-structured interviews based on pedigree charts. We also examined their knowledge or perception of colorectal cancer syndrome, levels of intimacy and whether or not they encouraged their relatives to have specific medical assessments. We found that 75% of the individuals advised their relatives to seek medical assessment, and any significant background factors that promoted such encouragement were observed. They tended to encourage first degree relatives and discuss the issue with other family members such as spouses before undertaking such attempts at encouragement. The reasons and methods of imparting encouragement were essentially identical. We also found that genetic testing for at-risk or more distant relatives was not encouraged so often. Therefore, providing individuals who have been tested for Lynch syndrome with opportunities for disseminating familial genetic information through appropriate genetic counseling is important.

The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64).

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus-like erythematous facial telangiectasia, sun sensitivity, infertility, stunted growth and a high predisposition to various types of cancer. Chromosomal abnormalities are hallmarks of this disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BLM is the causative gene for BS. We investigated the mutation in the BLM gene in 4 Japanese BS kindreds. Taken together with previously documented mutations, 2 kindreds were homozygous for 631delCAA and 2 were compound heterozygous for 631delCAA. The silent mutation of A1055C (Thr to Thr) was detected in control Japanese individuals. The 6-bp deletion/7-bp insertion at position 2,281, which most Askenazi Jewish BS patients carry, was not detected in 200 Japanese alleles. These results suggest that 631delCAA is a relatively common mutation among the Japanese BS patients.

About 60% of familial breast and ovarian cancers in Japan involve germline mutations of the BRCA1 or BRCA2 ( BRCA1/2) genes. These genes contribute to genetic stability and DNA repair and act as tumor suppressor genes. Mutation analysis of the BRCA1/2 genes has improved our understanding of both common mutation patterns in Japanese patients and the clinicopathological features of BRCA1/2-related cancers. BRCA1-related breast cancers are characterized by poor prognosis, a low rate of estrogen receptor positivity, and histological predominance of solid-tubular carcinoma. BRCA1-related ovarian cancers are associated with a high frequency of serous adenocarcinoma and a good outcome. Further large-scale studies are needed to delineate genotype-phenotype relations and penetrance in BRCA1/2-related breast and ovarian cancers in Japan. The development of systems for clinical genetics in Japan, including genetic counseling, has led to the increased use of genetic testing for the clinical management of BRCA1/2-related cancers. Three options are available for carriers of BRCA1/2 mutations: intensive surveillance, chemoprevention, and prophylactic surgery. Studies done in other countries indicate that prophylactic surgery effectively prevents the development of breast and ovarian cancers in carriers of BRCA1/2 mutations. However, prophylactic mastectomy remains controversial in Japan, and now systematic intensive surveillance is generally performed for the prevention of breast cancer in women at high risk. Early detection of ovarian cancer remains challenging, resulting in increased acceptance of the need for prophylactic oophorectomy in women at risk. This review summarizes experimental and clinical findings about familial breast and ovarian cancers, including data on Japanese patients.