Introduction

Familial adenomatous polyposis (FAP) is a hereditary form of colorectal cancer (CRC) characterized by the development of multiple adenomas in the colorectum from the age of 10 years. Without treatment, approximately 50% of individuals with classic FAP will develop CRC by the age of 40 years. Hence, prophylactic proctocolectomy is recommended, usually between the ages of 15 and 25 years [1,2,3]. Duodenal cancer and desmoid tumor can result in life-threatening conditions, including abdominal pain and obstruction of the small or large intestine [4, 5], which are the leading causes of death in patients with FAP [1, 6]. After prophylactic proctocolectomy, there are considerable postoperative complications such as fecal urgency, frequent bowel movements, sexual dysfunction, and altered body image owing to the scar and need for a colostomy bag. These complications and sequelae may cause psychological and social distress in the years following surgery [7,8,9].

Previous studies using self-reports have described the impact on patients’ future quality of life, employment, social activities, long-term relationships and marriage, attitudes toward having children, and family relationships [10]. Married status has been reported to positively influence one’s economic and social status, which in turn offers better health benefits [11]. In Japan, the marriage rate among people with physical, mental, and/or intellectual disorders is lower than that in the general population [12]. Given the psychological and social impacts of colorectal surgery, the marriage rate among patients with FAP may be low and the rate of postoperative childbirth among patients with FAP is unknown in Japan. Therefore, we investigated the marriage rate, postoperative marriage rate, and rate of postoperative childbirth among patients with FAP based on retrospective data derived from multiple Japanese centers.

Patients and methods

Patients

Patients with FAP are listed in a database of the Japanese Society for Cancer of the Colon and Rectum (JSCCR), which is maintained by each of the 35 JSCCR member institutions, the leading hospitals for colorectal treatment in Japan. The ethics committees of each author’s affiliated institution approved this study, which followed the principles laid down in the 1964 Declaration of Helsinki and its later amendments. We selected data from the working group of the JSCCR Multicenter Retrospective Study of Patients with FAP. To investigate the postoperative situation of patients with FAP, we collected data only for those diagnosed with FAP before 2018 [13]. The diagnostic criteria for FAP included a clinical diagnosis and/or genetic diagnosis. The criterion for a clinical diagnosis of FAP was either ≥100 adenomas in the colorectum, regardless of family history, or <100 adenomas plus a family history of FAP [14]. The criterion for a genetic diagnosis was germline variants in the APC gene.

A total of 632 patients with FAP were enrolled in this study. Among these, we excluded patients who had no colorectal surgery and no data on marital status. Finally, 161 patients were included in the study. Participants were divided into three categories according to marital status: married before surgery (N = 80), married after surgery (N = 13), and unmarried (N = 68). All 161 patients had undergone colorectal surgery, including for prophylactic proctocolectomy or cancer using an open or laparoscopic approach (Fig. 1). Prophylactic surgery was defined in patients who did not have stage I-IV CRC. Patients who had stage 0 CRC (carcinoma in situ) were included as having prophylactic surgery. We collected patient characteristics, including sex, birth year, age at FAP diagnosis, age at surgery, proband status, presence of any FAP-related extra-colonic lesions, purpose of surgery, presence of CRC, stage of CRC, surgical approach, surgical procedure, presence of permanent stoma, postoperative pregnancy, postoperative delivery, postoperative transvaginal delivery, postoperative erectile dysfunction, postoperative dysspermatism, and having undergone genetic testing. These data were collected from the medical records at each institution or directly from patients at the time of genetic counseling. Among the 161 patients, 75 (54 were missing) had received genetic counseling and 77 patients had undergone genetic testing. Marital status was classified into three groups: married before surgery, married after surgery, and unmarried, at the time of this study. Marital status was defined to be that at the time of participant registration, irrespective of any past divorce.

Fig. 1
figure 1

Flowchart of included patients. Included patients with FAP who had data on marital status were classified as married before colectomy, married after colectomy, and unmarried. FAP, familial adenomatous polyposis

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Statistical analysis

We used the chi-square test for categorical variables to compare characteristics between subgroups. The standardized marriage ratio was calculated as the number of married patients in the observed group divided by the expected number of married patients in the observed group. For comparisons of the marriage rate, with the general population as reference, we used public age- and sex-specific population data according to marital status in 2015, obtained from the 2015 Population Census [15]. To compare the cumulative marriage rate, we used public cumulative age-specific data for first-marriage rates according to the specific marriage statistics report of vital statistics in fiscal year 2016 from the Ministry of Health, Labour and Welfare of Japan [16]. The expected number of married patients was calculated as the sum of each category at the end of the observation period, as follows: the age-specific marriage rate in the standardized Japanese group, derived from the 2015 Population Census [15], multiplied by the age-specific marriage rate in the observed group. For patients who were unmarried before surgery, the expected number of married patients after colorectal surgery was the sum of each patient’s estimated score. Each patient’s estimated score for married status after colorectal surgery was the sum of the estimated score in each year from the age at the time of colorectal surgery to the end of the observation period, derived from the age-specific cumulative number of married people in the general Japanese population, which is in turn derived from cumulative age-specific first-marriage rates according to the specific marriage statistics report of vital statistics in fiscal year 2016 [16]. The standardized marital ratio (SMR) was the number of marriages observed in the FAP group divided by the expected number of marriages. The marriage rate among patients with physical, developmental, and mental disorders was derived from public data in the annual report on government measures for persons with disabilities (Summary) 2013 obtained from the Cabinet Office, Japan [12].

We conducted univariate and multivariable logistic regression analyses to clarify the factors associated with marital status after colorectal surgery. Covariates in the multivariable logistic regression model included: sex, birth year, proband status, presence of FAP-related extra-colonic lesions, purpose of surgery, presence of CRC, stage of CRC, surgical approach, surgical procedure, presence of permanent stoma, and having undergone genetic testing. Logistic regression analyses were also conducted, excluding patients with FAP who were married before colorectal surgery. We used a two-sided α level of 0.05. Statistical analyses were performed using JMP 16 software (SAS Institute, Cary, NC, USA).

Results

The characteristics and clinicopathological information of patients with FAP are shown in Table 1. The table shows the marriage rate among various sub-groups: patients with FAP; patients with FAP who were unmarried before surgery; the general Japanese population [15]; and patients with physical disabilities, intellectual disabilities, and mental disorders [12]. The marriage rate in all patients with FAP was 57.8%; this rate was 16.0% in those who were unmarried before surgery, and the marriage rate in the general population was 57.1%. The marriage rate in all patients with FAP was comparable to that in the general Japanese population. This rate in patients with FAP who were unmarried before surgery was lower than that in the total patients with FAP, the Japanese population, and in patients with physical disabilities. The SMR in all patients with FAP was also comparable to that of the general Japanese population (observed number of married patients with FAP = 93, expected number of married patients with FAP = 98.2; SMR 0.95, 95% confidence interval [CI] 0.75–1.14). The SMR in patients with FAP who were unmarried before surgery was not significantly lower than that in the general Japanese population, as derived from the Japanese cumulative marriage rate (observed married patients with FAP = 13, expected married patients with FAP = 17.4; SMR 0.75, 95% CI 0.34–1.15; Table 2).

Table 1 Patients’ characteristics
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Table 2 Marriage rate and standardized marriage ratio among FAP and other groups
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Table 3 shows the correlation of marital status with pregnancy and delivery. Among patients with FAP who were married after surgery, five of seven (71.4%) became pregnant and delivered after surgery. The rate of patients with FAP who were married after surgery was associated with postoperative pregnancy (p < 0.001), postoperative delivery (p < 0.001), and postoperative transvaginal delivery (p = 0.007). The information for five patients with FAP who achieved childbirth is listed in Supplemental Table 1. Four patients had prophylactic surgery: total colectomy with ileorectal anastomosis (IRA) = 2, partial colectomy = 1, proctocolectomy + ileal pouch–anal anastomosis (IPAA) = 1, and total colectomy with IRA because of double sigmoid cancer = 1.

Table 3 Pregnancy, delivery, and sexual function according to marital status
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In univariate logistic regression analyses, birth year ≥1980 and 1968–1979 were associated with less postoperative marriage compared to birth year ≤1967 (birth year 1968–1979, odds ratio [OR] 0.33, 95% CI 0.14–0.79, p = 0.013; ≥1980, OR 0.10, 95% CI 0.04–0.25, p < 0.001). Having undergone genetic testing (OR 2.43, 95% CI 1.27–4.63, p = 0.007) was positively associated with postoperative marriage. In multivariable logistic regression analysis, birth year ≥1980 were associated with less postoperative marriage compared to birth year ≤1967 (birth year ≥1980, OR 0.12, 95% CI 0.04–0.40, p < 0.001). Having undergone genetic testing (OR 4.06, 95% CI 1.72–9.60, p = 0.001) were positively associated with postoperative marriage (Table 4).

Table 4 Univariate and multivariable logistic regression analyses for marital status after surgery
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In multivariable logistic regression analyses, having undergone genetic testing (OR 2.94, 95% CI 0.88–10.1, p = 0.09) was positively associated with postoperative marriage in the group excluding patients with FAP who were married before surgery (Supplemental Table 2).

Discussion

Our findings demonstrated that the marriage rate among all 161 patients with FAP was 57.8% (SMR 0.95); however, the marriage rate in patients with FAP who were unmarried before surgery was 16% (SMR 0.75), which was likely lower than that in the Japanese population. This suggests that colorectal surgery may influence marriage after surgery in patients with FAP. However, the rate of postoperative pregnancy and delivery was 71.4% among patients with FAP who married after surgery, suggesting that colorectal surgery, including prophylactic surgery, may not lead to negative consequences in terms of fecundity.

The impact of surgery on quality of life can be particularly relevant given the changes in health among previously physically and mentally healthy young adults who have surgery for FAP [17]. One large study showed significantly lower quality-of-life scores in patients with FAP than those in the general population of the Netherlands using a standardized multidimensional questionnaire [18]. Regarding getting married and having children, a previous in-depth interview-based study among patients with FAP aged 18–35 years found that clinically affected individuals (who are potentially pathogenic variant carriers) have a number of major stressors, such as issues concerning physical functioning, discussing FAP with new potential marriage partners, and difficulties with decision-making regarding childbearing [10]. Moreover, a previous self-report questionnaire study among female patients with FAP aged 18–35 years revealed that 75% of respondents considered prenatal genetic testing and 21% considered termination of an affected pregnancy. Adolescent patients have been found to be at increased risk of experiencing poor psychological adaptation to hereditary cancer conditions [19], as well as chronic illnesses [20] and cancers [21]. Having to deal with the additional stress placed on an intimate relationship, the impact of possible fecundity problems, decision-making regarding childbearing, and the timing of discussing the risk of FAP with children have also been identified as being major issues faced by these individuals. These findings suggest that FAP could significantly impact younger adults regarding not only marriage but also having children [22, 23]. Whereas discrepancies between objective measures and subjective patient-perceived quality-of-life scores have frequently been observed [24, 25], quality-of-life scores do not simply reflect patients’ current state of health but may also be moderated by additional personal factors, such as resilience and social support. Although this study was an observational study and the association between surgery and postoperative marriage cannot be assessed, the postoperative marriage rate was likely low.

Psychological support, such as genetic counseling, may help individuals in making well-balanced decisions regarding undergoing prophylactic surgery and discussion with partners of topics such as getting married and having children in the future [26]. The Japanese Guideline for Clinical Practice of Hereditary Colorectal Cancer [14] states that genetic counseling can relieve anxiety in family members who have genetic problems by providing accurate medical knowledge in an easy-to-understand manner. Attention should also be paid to psychological effects and considerations regarding social discrimination experienced by patients and their family that may be brought about by the results of genetic testing. In this study, although the timing of counseling and its content was unknown, considering that genetic counseling was implemented based on this guideline, genetic counseling might have given patients with FAP and their families a positive mindset regarding marriage and childbirth.

Fertility preservation has been a concern among patients with FAP who undergo colorectal surgery at a young age owing to fears that IPAA may reduce fertility [27]. A Danish study showed that the 10% of women had an unfulfilled desire to become pregnant corresponded to the estimated population infertility rate [28]. A European study showed that the fecundability rate in female patients with FAP after IRA was not decreased, but fecundity was significantly decreased after IPAA in these women (OR 0.54) in comparison with the general population [29]. Compared with these studies, our data showed that five of seven (70%) patients became pregnant after surgery; three of these patients had IRA and one had IPAA (Supplemental Table 1). This suggests that fertility may not be reduced after surgery, but IPAA may influence a reduction in fertility. However, a large questionnaire study from the Netherlands showed that the risk of developing postoperative fertility problems was not associated with the type of surgery (IRA vs. IPAA), but it was associated with the first surgical procedure at a younger age [30]. In our study, no data on whether women with FAP were willing to have children and/or tried infertility treatment were available; however, 70% of our female patients with FAP who married after colorectal surgery experienced childbirth. Further studies of pregnancy and fertility in FAP using in-depth questionnaires and interviews are warranted.

This study had several limitations. First, this was an observational study and the association between colorectal surgery and postoperative marriage was not evaluated. Further studies investigating the association between surgery and postoperative marriage are necessary to clarify the reasons for the low postoperative marriage rate observed in this study. Second, there was selection bias in this study. Because the analyzed data were based on medical reports, we excluded patients with no data on marital status. Nevertheless, this is the first multicenter study in Japan to report data on the relationship between marital status and patients with FAP. Our findings will provide valuable information for clinicians, gastroenterologists, genetic counsellors, patient educators, and patients’ families or partners. Further prospective studies are necessary to confirm the results presented here and to more thoroughly investigate patient characteristics, mental health, and socioeconomic status. Third, the timing of genetic testing and counseling (i.e., whether before or after surgery) and the content of genetic counseling were unknown in this study. However, considering that genetic counseling was implemented based on the Japanese guideline [14], patients with FAP and their families might have had positive mindsets regarding marriage and future children after genetic testing and counseling. Although we had little information regarding genetic counseling, the findings of this observational study are important for understanding the effects of surgery on marriage and childbirth in patients with FAP. Fourth, we lacked data on not only age at marriage and age at pregnancy but also information on socioeconomic and mental status such as income, education, employment, depression, and other factors. Additionally, our data were limited regarding details of marital status, such as first or multiple marriages including divorce. Being married is generally associated with higher income, education, and employment [31, 32]. Genetic testing for FAP is a personal expense in the Japanese health insurance system, which suggests that selection bias of whether patients wanted to undergo genetic testing in this study. Moreover, as reported in the Japanese and U.S. studies, higher education, higher income, history of cancer, and knowledge of genetic testing were associated with an interest in genetic testing [33, 34], whether patients want to receive genetic testing can be influenced by not only level of income and education but also their personal characteristics and mental status; this information was lacking in this study.

In conclusion, the postoperative marriage rate among patients with FAP in our study was lower than that in the general Japanese population. However, fertility in female patients with FAP was preserved after colorectal surgery. Further research is needed to investigate the relationship among surgery, genetic counseling, and postoperative marital status.