Background/Objective: Adult survivors of childhood cancer can have altered social functioning. We sought to identify factors that predict marriage and divorce outcomes in this growing population.

Methods: This was a retrospective cohort study of 8,928 ≥5-year adult survivors of childhood malignancy and 2,879 random sibling controls participating in the Childhood Cancer Survivor Study. Marital status, current health, psychological status, and neurocognitive functioning were determined from surveys and validated instruments.

Results: Survivors were more likely to be never-married than siblings [relative risk (RR), 1.21; 95% confidence interval (95% CI), 1.15-1.26] and the U.S. population (RR, 1.25; 95% CI, 1.21-1.29), after adjusting for age, gender, and race. Patients with central nervous system tumors were at greatest risk of not marrying (RR, 1.50; 95% CI, 1.41-1.59). Married survivors divorced at frequencies similar to controls. In multivariable regression analysis, nonmarriage was most associated with cranial radiation (RR, 1.15; 95% CI, 1.02-1.31 for >2,400 centigray). In analysis of neurobehavioral functioning, nonmarriage was associated with worse task efficiency (RR, 1.27; 95% CI, 1.20-1.35), but not with emotional distress, or problems with emotional regulation, memory, or organization. Physical conditions predictive of nonmarriage included short stature (RR, 1.27; 95% CI, 1.20-1.34) and poor physical function (RR, 1.08; 95% CI, 1.00-1.18). Structural equation modeling suggested that cranial radiation influenced marriage status through short stature, cognitive problems, and poor physical function.

Conclusions: Childhood cancer survivors married at lower frequencies compared with peers. Patients with central nervous system tumors, cranial radiation, impaired processing efficiency, and short stature were more likely to never marry. Divorce patterns in survivors were similar to peers. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2626–35)

Approximately 80% of children with cancer will survive ≥5 years from diagnosis of their disease (1). The impact of cancer treatment on physical health during the first several decades following diagnosis and treatment has been well characterized, and survivors are known to be at increased risk of second neoplasms (2-4), cardiovascular disease (5, 6), endocrine dysfunction (6), and early death (7, 8). Several psychological sequelae have been described as well, with subgroups of survivors reporting depression (9-11), anxiety (10), and posttraumatic stress symptoms (12-14).

In addition to physical and mental health, attention must be given to the overall functioning of survivors in society. For instance, survivors have been shown to experience lower educational attainment (15), higher rates of unemployment (16, 17), and difficulty obtaining health insurance (16, 18). Although the institution of marriage has undergone many changes in modern times, it represents another social outcome that can be used to gauge the adaptation of survivors to life after cancer because it represents an aspiration for the majority of young adults in today's society (19). Relationships are challenging for all adults, but may be especially difficult for survivors, who struggle with the burdens of past disease. In one study, 29% of childhood cancer survivors cited disability or prior illness as a barrier to marriage (20). Uncertainty about future health may also impact survivor relationships (21-23).

The available literature on marriage outcomes after childhood cancer is characterized by inconsistent findings, likely resulting from the limited size and/or distinct composition of the study populations (24-29). Moreover, many of the earlier reports did not assess the underlying causes of observed patterns or have appropriate comparisons to noncancer populations. Most recently in 2007, Frobisher et al. reported reduced marriage frequencies in 9,954 British childhood cancer survivors diagnosed from 1940 to 1991 compared with those expected from the general population and concluded that survivors were less likely to get married (30). Although this study was large, there was limited measurement of emotional and cognitive functioning as potential mediators of decreased marriage frequencies. Also, a key marital outcome, divorce, was not examined.

The Childhood Cancer Survivor Study (CCSS) provides a unique opportunity to add to our understanding of marriage outcomes because of the size and characterization of the cohort, as well as the availability of a sibling comparison group. In this article, we (a) describe marriage and divorce frequencies in childhood cancer survivors from the CCSS cohort, with comparison with both a sibling cohort and data from the U.S. Census; and (b) identify patient and treatment factors that predict marital status, including psychosocial distress and neurocognitive impairment.

Study Population

CCSS Cohort

The CCSS is a 26-institution retrospective cohort of survivors of childhood cancer designed to study the late effects of cancer therapy. Eligibility criteria included: (a) diagnosis of leukemia, central nervous system (CNS) tumor, Hodgkin's lymphoma, non-Hodgkin disease, Wilms' tumor, neuroblastoma, soft tissue sarcoma, or bone tumor; (b) diagnosis and initial treatment at a participating center; (c) diagnosis between January 1, 1970, and December 31, 1986; (d) age <21 y at diagnosis; and (e) survival of ≥5 y after diagnosis. The methodology has been previously described (31) and study documents are available.8

Each participating center's institutional review board reviewed and approved the CCSS protocol and contact documents.

Starting in August 1994, participants completed an extensive baseline questionnaire that included demographic characteristics, marital status, and health history. Two subsequent surveys were administered (2000 survey, beginning in May 2000; 2003 survey, beginning in November 2002) to obtain updated information. Trained data abstractors reviewed the participants' medical records for detailed cancer diagnosis and treatment information.

Of the 20,691 patients eligible for participation, 14,363 completed the baseline questionnaire, 3,058 were lost to follow-up, and 3,205 refused participation. Of the 14,363 initial participants, 10,366 completed the first follow-up questionnaire (2000 survey) and 9,308 completed the second follow-up questionnaire (2003 survey). Cases were excluded from the current analysis if they were <15 y (n = 3) or if they were married prior to diagnosis of malignancy (n = 75), yielding 9,230 individuals, of whom 8,928 had known marital status.

Siblings

A random sample of participating survivors (n = 6,005) was asked to contact their sibling closest in age for participation in the study. Of these, 3,839 siblings completed the baseline (enrollment) survey, 2,540 completed the 2000 survey, and 2,951 completed the 2003 survey. For the current analysis, siblings were restricted to those subjects age ≥15 y, alive, and in follow-up as of the 2003 survey, resulting in 2,789 siblings with known marital status. Table 1 shows the case characteristics compared with siblings.

Table 1.

Characteristics of the Childhood Cancer Survivor Study cases and siblings

CCSS cohortSibling cohortP2)
n (%)n (%)
Diagnosis 
    Leukemia 3,159 (34.2)  N/A 
    Central nervous tumor 1,171 (12.7)   
    Hodgkin disease 1,151 (12.5)   
    Non-Hodgkin lymphoma 697 (7.6)   
    Kidney (Wilms) 868 (9.4)   
    Neuroblastoma 629 (6.8)   
    Soft tissue sarcoma 809 (8.8)   
    Bone cancer 746 (8.1)   
Sex 
    Male 4,695 (50.9) 1,315 (46.1) <0.0001 
    Female 4,535 (49.1) 1,537 (53.9)  
Age at last contact (y) 
    15-19 338 (3.7) 147 (5.2) <0.0001 
    20-24 1,742 (18.9) 415 (14.6)  
    25-29 1,982 (21.5) 522 (18.3)  
    30-34 2,131 (23.1) 531 (18.6)  
    35-39 1,640 (17.8) 510 (17.9)  
    ≥40 1,397 (15.1) 727 (25.5)  
Race/ethnicity 
    White non-Hispanic 7,895 (85.9) 2,532 (91.9) <0.0001 
    Other 1,299 (14.1) 222 (8.1)  
Education 
    Did not complete high school 458 (5.0) 122 (4.3) <0.0001 
    Completed high school 4,814 (52.7) 1,313 (46.2)  
    College graduate 3,859 (42.3) 1,408 (49.5)  
Household income 
    <$40,000 2,905 (32.4) 637 (22.9) <0.0001 
    ≥$40,000 6,062 (67.6) 2,149 (77.1)  
Personal income 
    <$40,000 6,625 (75.0) 1,574 (63.1) <0.0001 
    ≥$40,000 2,205 (25.0) 921 (36.9)  
Employment status 
    Unemployed 428 (4.7) 69 (2.4) <0.0001 
    Disabled 708 (7.8) 37 (1.3)  
    Employed or retired 7,895 (87.4) 2,718 (96.2)  
CCSS cohortSibling cohortP2)
n (%)n (%)
Diagnosis 
    Leukemia 3,159 (34.2)  N/A 
    Central nervous tumor 1,171 (12.7)   
    Hodgkin disease 1,151 (12.5)   
    Non-Hodgkin lymphoma 697 (7.6)   
    Kidney (Wilms) 868 (9.4)   
    Neuroblastoma 629 (6.8)   
    Soft tissue sarcoma 809 (8.8)   
    Bone cancer 746 (8.1)   
Sex 
    Male 4,695 (50.9) 1,315 (46.1) <0.0001 
    Female 4,535 (49.1) 1,537 (53.9)  
Age at last contact (y) 
    15-19 338 (3.7) 147 (5.2) <0.0001 
    20-24 1,742 (18.9) 415 (14.6)  
    25-29 1,982 (21.5) 522 (18.3)  
    30-34 2,131 (23.1) 531 (18.6)  
    35-39 1,640 (17.8) 510 (17.9)  
    ≥40 1,397 (15.1) 727 (25.5)  
Race/ethnicity 
    White non-Hispanic 7,895 (85.9) 2,532 (91.9) <0.0001 
    Other 1,299 (14.1) 222 (8.1)  
Education 
    Did not complete high school 458 (5.0) 122 (4.3) <0.0001 
    Completed high school 4,814 (52.7) 1,313 (46.2)  
    College graduate 3,859 (42.3) 1,408 (49.5)  
Household income 
    <$40,000 2,905 (32.4) 637 (22.9) <0.0001 
    ≥$40,000 6,062 (67.6) 2,149 (77.1)  
Personal income 
    <$40,000 6,625 (75.0) 1,574 (63.1) <0.0001 
    ≥$40,000 2,205 (25.0) 921 (36.9)  
Employment status 
    Unemployed 428 (4.7) 69 (2.4) <0.0001 
    Disabled 708 (7.8) 37 (1.3)  
    Employed or retired 7,895 (87.4) 2,718 (96.2)  

Abbreviation: N/A, not applicable.

U.S. Population

Data on marital status of the U.S. population were obtained from the 2002 Current Population Survey (CPS), as issued by the Bureau of Census. The report includes marital status, stratified by gender, current age (≥15 y), education, and race.9

Measures

On each CCSS survey questionnaire, participants categorized themselves as single/never married, married, living as married, widowed, divorced, or separated/no longer living as married. Reponses were grouped into three outcomes: never-married, currently-divorced, and ever-divorced. Never-married was available from the 2003 survey. Subjects responding divorced or separated in the 2003 survey were defined as currently-divorced, consistent with past studies (24, 32). Cases who reported themselves as divorced or separated in any survey were classified as ever-divorced. It is possible that an individual responding married in consecutive surveys may have in fact been divorced and remarried. We anticipate that the number of divorce cases missed in this manner will be negligible, given a median time of 5 y between the baseline and the 2000 survey, and about 2 y between the 2000 and the 2003 surveys.

In the 2002 CPS, never-married and currently-divorced were clearly defined; ever-divorced was not available. Also, the CPS did not include a “living with partner as married” category. Therefore, when drawing comparison with the general population, cohort members in the “living with partner as married” category as of the 2003 survey were considered never-married.

Data from the 2003 survey were used for variables that change with time, including education, income, employment status, and height. Diminished height was defined as height below the tenth percentile for age, gender, and ethnicity, as reported by the Centers for Disease Control and Prevention.10

Perceived infertility was defined as “yes” to the question, “Has a doctor ever told you that you might have trouble having children?”

Psychological health was evaluated in the baseline and the 2003 survey with the Brief Symptom Inventory-18 (BSI-18), an 18-item checklist that measures symptoms of anxiety, depression, and somatic distress (33). Responses were scored to generate a global severity index (GSI) score (34). In our analysis, subjects with GSI elevations ≥50 on either of two BSI-18 administrations were classified as having a positive history of psychological distress, consistent with a previous validation study in cancer survivors by Recklitis et al. (35).

Neurocognitive functioning, including executive skills, was evaluated with the CCSS Neurocognitive Questionnaire, a 25-item instrument that is predominantly a subset of items from an early investigational version of the Behavior Rating Inventory of Executive Functioning-Adult version. Krull et al identified four domains that showed good internal consistency: task efficiency, emotional regulation, organization, and memory skills (36). Subjects were classified as high risk for neurocognitive dysfunction if the response on any of the questions for the respective factor was “often a problem” consistent with validation studies of this instrument.

Analyses

Frequencies of never-married and currently-divorced were described in CCSS cases and compared with frequencies for siblings and the U.S. population (as of the 2002 CPS), overall and in a stratified fashion, by age and gender. The currently-divorced proportion was calculated as the number divorced or separated, divided by the total number of married, widowed, divorced, or separated. Likelihood ratio tests were used to determine the statistical significance of differences between groups. Survivors were compared with U.S. population data and to the sibling comparison group. Generalized estimating equation formulations of the model and significance tests were utilized to account for the intrafamily correlation between survivors and siblings (37)

Among survivors, case-case comparisons were conducted with respect to the outcomes never-married and ever-divorced. The analysis of ever-divorced was restricted to those subjects who had been married at least once and who had reported marital status in all three surveys. Log-binomial regression models were used to evaluate associations between explanatory variables and each outcome. These models allow direct calculation of age-adjusted relative risks (RR) with 95% confidence intervals (95% CI) to compare the probability of outcomes between survivor sub-groups and were selected over logistic regression due to the high prevalence of the outcome (38). Multivariable regression models, including factors marginally significant in the unadjusted analysis (P < 0.2), were created to determine the independent role of each variable, adjusted for age at diagnosis, gender, and educational status. Potential confounders and interactions were also evaluated.

Structural equation models of the observed data [weighted least-square parameter estimates (δ parameterization)] were analyzed using Mplus 5.2 software (39). All variables were directly observed measures; there were no latent variables. Never-married (n= 2,616) and ever-married (n = 3,924) subsamples at the follow-up 2 survey with complete data made up the final sample for the SE analysis. We chose to use samples with complete data rather than use data imputation in order to avoid potentially distorting coefficients of association and correlation relating variables (40). The best-fitting model was determined according to the following criteria: (a) conceptually sound; (b) statistically significant parameter estimates that represent the strength of the path between two variables (read as standardized regression coefficients); (c) meets the established SE fit criteria [nonsignificant χ2 statistic (P > 0.05)]; (d) root mean square error of approximation (RMSEA) ≤0.05; (e) weighted root mean square residual (WRMR) <1.0 (41, 42); (f) comparative fit index (CFI) and Tucker Lewis index (TLI) ≥0.90 (43); and (g) the highest percentage of explained variance for the outcome.

Marital Status of CCSS Cohort at Last Contact

At last contact, 42.4% (n = 3,783) of survivors were currently married, 7.3% (n = 654) were divorced or separated, 0.2% (n = 20) were widowed, and 46.4% (n = 4,141) had never been married. Of those who had never married (n = 3,698), 90% were living as single and 10% lived with a partner outside of marriage.

Comparison of Survivor Marital Status with Siblings and the U.S. Population

Survivors were significantly more likely to never have married than siblings (RR, 1.21; 95% CI, 1.15-1.26) and the U.S. population (RR, 1.25; 95% CI, 1.21-1.29), after adjusting for age, gender, and race (Tables 2 and 3). The trend was apparent across all age groups ≥25 years old. It was particularly marked for those in the 35- to 44-year and ≥45-year age groups, where survivors were 1.90 (95% CI, 1.55-2.32) and 2.35 (95% CI, 1.29-4.28) times more likely than siblings to be never married, after adjusting for gender and race (data not shown). Cases with a history of CNS tumor (RR, 1.49; 95% CI, 1.40-1.58) and leukemia (RR, 1.19; 95% CI, 1.12-1.25) had the greatest likelihood of never marrying. Upon further stratification, the probability of never marrying remained elevated in leukemia patients who received cranial radiation (RR, 1.25; 95% CI, 1.18-1.32), but not in those treated with chemotherapy only (RR, 1.03; 95% CI, 0.96-1.10).

Table 2.

Frequencies of never-married status: comparison of survivors with siblings and the U.S. census population, adjusted for race

SurvivorsSiblingsU.S Census
n (%)n (%)%
All ages, 18-54 y 
    Total 3,856 (46.1) 821 (31.7)* 32.4 
    Male 2,083 (49.2) 421 (35.3)* 36.5 
    Female 1,773 (43.0) 400 (28.6)* 24.7 
Age 18-24 y 
    Total 1,444 (85.3) 371 (83.7) 84.4 
    Male 726 (89.9) 183 (88.4) 86.5 
    Female 718 (81.1) 188 (79.7) 79.7 
Age 25-34 y 
    Total 1,841 (48.2) 338 (34.7)* 37.2 
    Male 1,028 (52.4) 186 (39.9)* 41.8 
    Female 813 (43.7) 152 (29.9)* 27.5 
Age 35-44 y 
    Total 524 (21.5) 99 (11.0)* 15.9 
    Male 304 (24.1) 46 (11.2)* 19.4 
    Female 220 (18.7) 53 (10.9)* 9.7 
Age 45-54 y 
    Total 47 (11.5) 13 (4.8)* 10.0 
    Male 25 (12.0) 6 (5.6) 11.9 
    Female 22 (11.1) 7 (4.3)* 6.9 
SurvivorsSiblingsU.S Census
n (%)n (%)%
All ages, 18-54 y 
    Total 3,856 (46.1) 821 (31.7)* 32.4 
    Male 2,083 (49.2) 421 (35.3)* 36.5 
    Female 1,773 (43.0) 400 (28.6)* 24.7 
Age 18-24 y 
    Total 1,444 (85.3) 371 (83.7) 84.4 
    Male 726 (89.9) 183 (88.4) 86.5 
    Female 718 (81.1) 188 (79.7) 79.7 
Age 25-34 y 
    Total 1,841 (48.2) 338 (34.7)* 37.2 
    Male 1,028 (52.4) 186 (39.9)* 41.8 
    Female 813 (43.7) 152 (29.9)* 27.5 
Age 35-44 y 
    Total 524 (21.5) 99 (11.0)* 15.9 
    Male 304 (24.1) 46 (11.2)* 19.4 
    Female 220 (18.7) 53 (10.9)* 9.7 
Age 45-54 y 
    Total 47 (11.5) 13 (4.8)* 10.0 
    Male 25 (12.0) 6 (5.6) 11.9 
    Female 22 (11.1) 7 (4.3)* 6.9 

*Indicates P < 0.05, survivors vs. siblings.

Indicates P < 0.05, survivors vs. U.S. Census.

Table 3.

Relative risk of never-married and ever-divorced in CCSS cases compared with sibling comparison group, overall and stratified by cancer diagnosis, adjusted by age at evaluation, gender, and race

Never-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
All cancers 3,698 (41.4) 1.21 (1.15-1.26) <0.0001 981 (21.4) 1.08 (0.96-1.21) 0.20 
Leukemia 1,508 (49.2) 1.19 (1.12-1.25) <0.0001 282 (20.8) 1.09 (0.94-1.27) 0.26 
Central nervous tumor 698 (62.5) 1.49 (1.40-1.58) <0.0001 78 (21.5) 1.07 (0.86-1.34) 0.553 
Non-Hodgkin lymphoma 204 (29.6) 1.09 (0.98-1.22) 0.13 104 (24.4) 1.19 (0.97-1.46) 0.10 
Kidney (Wilms) 377 (46.2) 0.97 (0.90-1.04) 0.41 56 (14.4) 0.80 (0.60-1.07) 0.14 
Neuroblastoma 333 (59.9) 1.14 (1.06-1.22) 0.0002 38 (19.8) 1.17 (0.86-1.60) 0.32 
Soft tissue sarcoma 270 (33.9) 1.11 (1.02-1.21) 0.02 87 (19.4) 0.93 (0.75-1.15) 0.50 
Bone cancer 149 (20.1) 1.02 (0.87-1.19) 0.02 120 (22.6) 1.03 (0.85-1.24) 0.78 
Hodgkin disease 159 (13.9) 1.05 (0.91-1.21) 0.54 216 (24.4) 1.13 (0.96-1.33) 0.13 
Sibling comparison group 776 (27.8) Ref N/A 304 (19.9) Ref N/A 
Never-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
All cancers 3,698 (41.4) 1.21 (1.15-1.26) <0.0001 981 (21.4) 1.08 (0.96-1.21) 0.20 
Leukemia 1,508 (49.2) 1.19 (1.12-1.25) <0.0001 282 (20.8) 1.09 (0.94-1.27) 0.26 
Central nervous tumor 698 (62.5) 1.49 (1.40-1.58) <0.0001 78 (21.5) 1.07 (0.86-1.34) 0.553 
Non-Hodgkin lymphoma 204 (29.6) 1.09 (0.98-1.22) 0.13 104 (24.4) 1.19 (0.97-1.46) 0.10 
Kidney (Wilms) 377 (46.2) 0.97 (0.90-1.04) 0.41 56 (14.4) 0.80 (0.60-1.07) 0.14 
Neuroblastoma 333 (59.9) 1.14 (1.06-1.22) 0.0002 38 (19.8) 1.17 (0.86-1.60) 0.32 
Soft tissue sarcoma 270 (33.9) 1.11 (1.02-1.21) 0.02 87 (19.4) 0.93 (0.75-1.15) 0.50 
Bone cancer 149 (20.1) 1.02 (0.87-1.19) 0.02 120 (22.6) 1.03 (0.85-1.24) 0.78 
Hodgkin disease 159 (13.9) 1.05 (0.91-1.21) 0.54 216 (24.4) 1.13 (0.96-1.33) 0.13 
Sibling comparison group 776 (27.8) Ref N/A 304 (19.9) Ref N/A 

NOTE: There is no referent within the diagnostic category; every row is compared with the sibling group.

Survivors divorced at similar frequencies to siblings (RR, 1.08; 95% CI, 0.96-1.21) and to population controls (RR, 0.96; 95% CI, 0.89-1.03; P = 0.23). No cancer diagnosis group had an elevated risk of divorce (Table 3). No statistically significant differences in divorce frequencies were observed across age or gender groups (data not shown).

Predictors of Never-Married Status in Survivors

Univariate analysis adjusted for gender and age at last contact and gender indicated that age <13 years at diagnosis (RR, 1.52; 95% CI, 1.34-1.72) and cranial radiation >2,400 centigray (RR compared with no cranial radiation, 1.28; 95% CI, 1.14-1.43) were the strongest predictors of nonmarriage among treatment factors (Table 4). The following medical and neuropsychological conditions were significantly associated with never marrying (Table 4): short stature, history of tumor recurrence, poor self-reported physical functioning, emotional distress, problems with task efficiency, problems with organization, and problems with memory. Report of a perceived fertility problem was associated with a lower likelihood of not marrying (RR, 0.91; 95% CI, 0.87-0.95).

Table 4.

Univariate analysis of the association of patient factors, cancer treatment, and medical conditions with marital status, adjusted for gender and age at last contact

CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis (y) 
    <13 3,338 (50.6) 1.52 (1.34-1.72) <0.0001 580 (20.5) 1.12 (0.98-1.28) 0.10 
    13-20 360 (15.4)  401 (22.7)  
Gender 
    Female 1,692 (38.5)  524 (22.0)  
    Male 2,006 (44.2) 1.16 (1.12-1.21) <0.0001 457 (20.7) 0.92 (0.82-1.03) 0.13 
Diagnosis 
    Leukemia 1,508 (49.2) 1.87 (1.60-2.17) <0.0001 282 (20.8) 0.97 (0.82-1.15) 0.73 
    Central nervous tumor 698 (62.5) 2.22 (1.90-2.59) <0.0001 78 (21.5) 0.96 (0.76-1.20) 0.70 
    Non-Hodgkin lymphoma 204 (29.6) 1.56 (1.31-1.86) <0.0001 104 (24.4) 1.07 (0.87-1.31) 0.55 
    Kidney (Wilms) 377 (46.2) 1.59 (1.35-1.88) <0.0001 56 (14.4) 0.73 (0.55-0.97) 0.03 
    Neuroblastoma 333 (59.9) 1.96 (1.67-2.30) <0.0001 38 (19.8) 1.00 (0.73-1.38) 0.99 
    Soft tissue sarcoma 270 (33.9) 1.69 (1.42-2.00) <0.0001 87 (19.4) 0.84 (0.68-1.05) 0.14 
    Bone cancer 149 (20.1) 1.33 (1.09-1.62) 0.005 120 (22.6) 0.94 (0.77-1.14) 0.54 
    Hodgkin disease 159 (13.9)  216 (24.4)  
Cranial radiation (centigray) 
    >2,400 89 (54.6) 1.28 (1.14-1.43) <0.0001 9 (14.5) 0.68 (0.37-1.26) 0.23 
    >0 and ≤2,400 726 (49.6) 1.10 (1.04-1.17) 0.001 128 (19.5) 1.01 (0.83-1.22) 0.92 
    0 1150 (42.5)  273 (19.8)  
Stem cell transplant 
    Yes 37 (44.0) 0.96 (0.81-1.15) 0.70 7 (16.7) 0.81 (0.41-1.59) 0.53 
    No 3,355 (41.6)  867 (20.8)  
Treatment duration 
    ≥2 y 1,884 (45.1) 1.06 (1.01-1.10) 0.01 409 (20.1) 0.98 (0.87-1.10) 0.69 
    <2 y 1,386 (37.6)  434 (21.2)  
Perceived fertility problem 
    Yes 1,208 (33.8) 0.91 (0.87-0.95) <0.0001 481 (23.2) 1.14 (1.01-1.27) 0.03 
    No 2,262 (45.8)  466 (19.7)  
Short stature 
    Yes 978 (57.2) 1.20 (1.16-1.24) <0.0001 150 (23.7) 1.16 (0.99-1.35) 0.07 
    No 2,571 (37.0)  810 (20.9)  
Subsequent malignant neoplasm 
    Yes 220 (27.8) 1.05 (0.97-1.15) 0.24 114 (21.6) 0.91 (0.77-1.09) 0.31 
    No 3478 (42.7)  867 (21.3)  
Recurrence 
    Yes 415 (45.8) 1.11 (1.06-1.17) <0.0001 93 (21.7) 0.98 (0.82-1.19) 0.87 
    No 3,283 (40.9)  888 (21.3)  
Poor physical function (SF-36 T-score <40) 
    Yes 375 (42.9) 1.19 (1.14-1.24) <0.0001 141 (31.7) 1.52 (1.30-1.78) <0.0001 
    No 2,717 (40.9)  687 (19.6)  
Emotional distress (GSI T-score ≥50) 
    Yes 1,613 (39.9) 1.08 (1.03-1.12) 0.0007 544 (25.3) 1.40 (1.25-1.57) <0.0001 
    No 1,513 (36.8)  412 (18.0)  
NCQ: problems with task efficiency 
    Yes 935 (49.4) 1.17 (1.12-1.22) <0.0001 220 (25.4) 1.37 (1.20-1.58) <0.0001 
    No 1,637 (35.6)  500 (18.5)  
NCQ: problems with organization 
    Yes 550 (44.4) 1.10 (1.04-1.15) 0.0002 141 (22.7) 1.13 (0.96-1.32) 0.15 
    No 2,022 (38.5)  579 (19.7)  
NCQ: problems with memory 
    Yes 581 (43.5) 1.06 (1.01-1.12) 0.02 174 (25.9) 1.34 (1.16-1.56) 0.0001 
    No 1,991 (38.6)  546 (18.9)  
NCQ: problems with emotional regulation 
    Yes 666 (41.8) 0.99 (0.94-1.04) 0.69 205 (24.6) 1.32 (1.15-1.52) 0.0001 
    No 1,906 (38.9)  515 (18.9)  
Educational attainment 
    Did not complete high school 193 (50.4) 1.04 (0.96-1.13) 0.40 45 (31.7) 2.15 (1.66-2.78) <0.0001 
    Completed high school 2,139 (46.2) 1.04 (1.00-1.09) 0.08 579 (26.8) 1.80 (1.60-2.03) <0.0001 
    College graduate 1,323 (34.4)  352 (15.5)  
CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis (y) 
    <13 3,338 (50.6) 1.52 (1.34-1.72) <0.0001 580 (20.5) 1.12 (0.98-1.28) 0.10 
    13-20 360 (15.4)  401 (22.7)  
Gender 
    Female 1,692 (38.5)  524 (22.0)  
    Male 2,006 (44.2) 1.16 (1.12-1.21) <0.0001 457 (20.7) 0.92 (0.82-1.03) 0.13 
Diagnosis 
    Leukemia 1,508 (49.2) 1.87 (1.60-2.17) <0.0001 282 (20.8) 0.97 (0.82-1.15) 0.73 
    Central nervous tumor 698 (62.5) 2.22 (1.90-2.59) <0.0001 78 (21.5) 0.96 (0.76-1.20) 0.70 
    Non-Hodgkin lymphoma 204 (29.6) 1.56 (1.31-1.86) <0.0001 104 (24.4) 1.07 (0.87-1.31) 0.55 
    Kidney (Wilms) 377 (46.2) 1.59 (1.35-1.88) <0.0001 56 (14.4) 0.73 (0.55-0.97) 0.03 
    Neuroblastoma 333 (59.9) 1.96 (1.67-2.30) <0.0001 38 (19.8) 1.00 (0.73-1.38) 0.99 
    Soft tissue sarcoma 270 (33.9) 1.69 (1.42-2.00) <0.0001 87 (19.4) 0.84 (0.68-1.05) 0.14 
    Bone cancer 149 (20.1) 1.33 (1.09-1.62) 0.005 120 (22.6) 0.94 (0.77-1.14) 0.54 
    Hodgkin disease 159 (13.9)  216 (24.4)  
Cranial radiation (centigray) 
    >2,400 89 (54.6) 1.28 (1.14-1.43) <0.0001 9 (14.5) 0.68 (0.37-1.26) 0.23 
    >0 and ≤2,400 726 (49.6) 1.10 (1.04-1.17) 0.001 128 (19.5) 1.01 (0.83-1.22) 0.92 
    0 1150 (42.5)  273 (19.8)  
Stem cell transplant 
    Yes 37 (44.0) 0.96 (0.81-1.15) 0.70 7 (16.7) 0.81 (0.41-1.59) 0.53 
    No 3,355 (41.6)  867 (20.8)  
Treatment duration 
    ≥2 y 1,884 (45.1) 1.06 (1.01-1.10) 0.01 409 (20.1) 0.98 (0.87-1.10) 0.69 
    <2 y 1,386 (37.6)  434 (21.2)  
Perceived fertility problem 
    Yes 1,208 (33.8) 0.91 (0.87-0.95) <0.0001 481 (23.2) 1.14 (1.01-1.27) 0.03 
    No 2,262 (45.8)  466 (19.7)  
Short stature 
    Yes 978 (57.2) 1.20 (1.16-1.24) <0.0001 150 (23.7) 1.16 (0.99-1.35) 0.07 
    No 2,571 (37.0)  810 (20.9)  
Subsequent malignant neoplasm 
    Yes 220 (27.8) 1.05 (0.97-1.15) 0.24 114 (21.6) 0.91 (0.77-1.09) 0.31 
    No 3478 (42.7)  867 (21.3)  
Recurrence 
    Yes 415 (45.8) 1.11 (1.06-1.17) <0.0001 93 (21.7) 0.98 (0.82-1.19) 0.87 
    No 3,283 (40.9)  888 (21.3)  
Poor physical function (SF-36 T-score <40) 
    Yes 375 (42.9) 1.19 (1.14-1.24) <0.0001 141 (31.7) 1.52 (1.30-1.78) <0.0001 
    No 2,717 (40.9)  687 (19.6)  
Emotional distress (GSI T-score ≥50) 
    Yes 1,613 (39.9) 1.08 (1.03-1.12) 0.0007 544 (25.3) 1.40 (1.25-1.57) <0.0001 
    No 1,513 (36.8)  412 (18.0)  
NCQ: problems with task efficiency 
    Yes 935 (49.4) 1.17 (1.12-1.22) <0.0001 220 (25.4) 1.37 (1.20-1.58) <0.0001 
    No 1,637 (35.6)  500 (18.5)  
NCQ: problems with organization 
    Yes 550 (44.4) 1.10 (1.04-1.15) 0.0002 141 (22.7) 1.13 (0.96-1.32) 0.15 
    No 2,022 (38.5)  579 (19.7)  
NCQ: problems with memory 
    Yes 581 (43.5) 1.06 (1.01-1.12) 0.02 174 (25.9) 1.34 (1.16-1.56) 0.0001 
    No 1,991 (38.6)  546 (18.9)  
NCQ: problems with emotional regulation 
    Yes 666 (41.8) 0.99 (0.94-1.04) 0.69 205 (24.6) 1.32 (1.15-1.52) 0.0001 
    No 1,906 (38.9)  515 (18.9)  
Educational attainment 
    Did not complete high school 193 (50.4) 1.04 (0.96-1.13) 0.40 45 (31.7) 2.15 (1.66-2.78) <0.0001 
    Completed high school 2,139 (46.2) 1.04 (1.00-1.09) 0.08 579 (26.8) 1.80 (1.60-2.03) <0.0001 
    College graduate 1,323 (34.4)  352 (15.5)  

Abbreviation: NCQ, CCSS Neurocognitive Questionnaire.

Tables 5 to 7 display the results of three separate multivariable models, all of which included gender, age at last contact, age at diagnosis, and educational attainment, divided into disease and treatment factors, neurobehavioral functioning, and physical functioning factors. Significant disease and treatment predictors of nonmarriage included cranial radiation >2,400 centigray (RR compared with no radiation, 1.15; 95% CI, 1.02-1.31) and history of recurrence (RR, 1.10; 95% CI, 1-1.20). Impaired task efficiency was the only neurobehavioral condition significantly associated with not being married in adjusted analysis (RR, 1.27; 95% CI, 1.20-1.35). Problems with emotional regulation were associated with a greater likelihood of getting married. In terms of physical conditions, short stature (RR, 1.27; 95% CI, 1.2-1.34) and poor self-reported physical functioning (RR, 1.08; 95% CI, 1-1.18) were associated with not ever marrying. Perceived fertility problem was not included in the adjusted model because the direction of the association suggested that fertility status likely was determined after marriage.

Table 5.

Multivariable regression model of the association between disease and treatment factors with marital status, adjusted for gender and age at last contact

CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis 
    <13 y 3,338 (50.6) 1.38 (1.14-1.67) 0.0008 580 (20.5) 1.28 (1.03-1.60) 0.03 
    13-20 y 360 (15.4)  401 (22.7)  
Gender 
    Female 1,692 (38.5) <0.0001 524 (22.0) 0.04 
    Male 2,006 (44.2) 1.13 (1.06-1.19)  457 (20.7) 0.83 (0.70-0.99)  
Educational attainment 
    Did not complete high school 193 (50.4) 1.14 (1.00-1.30) 0.04 45 (31.7) 2.58 (1.80-3.70) <0.0001 
    Completed high school 2139 (46.2) 1.12 (1.05-1.20) 0.0003 579 (26.8) 1.79 (1.49-2.17) <0.0001 
    College graduate 1323 (34.4)  352 (15.5)  
Cranial radiation (centigray) 
    >2,400 89 (54.6) 1.15 (1.02-1.31) 0.03 9 (14.5) 0.60 (0.32-1.11) 0.10 
    >0 and ≤2400 726 (49.6) 1.03 (0.97-1.11) 0.33 128 (19.5) 0.91 (0.73-1.13) 0.40 
    0 1,150 (42.5) 1.00  273 (19.8)  
Stem cell transplant 
    Yes 37 (44.0) 1.05 (0.82-1.34) 0.71 7 (16.7) 1.6 (0.61-4.19) 0.33 
    No 3,355 (41.6)  867 (20.8) 
Treatment duration (y) 
    ≥2 y 1,884 (45.1) 1.04 (0.97-1.12) 0.29 409 (20.1) 1.05 (0.85-1.30) 0.67 
    <2 y 1,386 (37.6)  434 (21.2) 
Recurrence 
    Yes 415 (45.8) 1.10 (1.01-1.2) 0.04 93 (21.7) 0.96 (0.70-1.32) 0.82 
    No 3,283 (40.9)  888 (21.3)  
CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis 
    <13 y 3,338 (50.6) 1.38 (1.14-1.67) 0.0008 580 (20.5) 1.28 (1.03-1.60) 0.03 
    13-20 y 360 (15.4)  401 (22.7)  
Gender 
    Female 1,692 (38.5) <0.0001 524 (22.0) 0.04 
    Male 2,006 (44.2) 1.13 (1.06-1.19)  457 (20.7) 0.83 (0.70-0.99)  
Educational attainment 
    Did not complete high school 193 (50.4) 1.14 (1.00-1.30) 0.04 45 (31.7) 2.58 (1.80-3.70) <0.0001 
    Completed high school 2139 (46.2) 1.12 (1.05-1.20) 0.0003 579 (26.8) 1.79 (1.49-2.17) <0.0001 
    College graduate 1323 (34.4)  352 (15.5)  
Cranial radiation (centigray) 
    >2,400 89 (54.6) 1.15 (1.02-1.31) 0.03 9 (14.5) 0.60 (0.32-1.11) 0.10 
    >0 and ≤2400 726 (49.6) 1.03 (0.97-1.11) 0.33 128 (19.5) 0.91 (0.73-1.13) 0.40 
    0 1,150 (42.5) 1.00  273 (19.8)  
Stem cell transplant 
    Yes 37 (44.0) 1.05 (0.82-1.34) 0.71 7 (16.7) 1.6 (0.61-4.19) 0.33 
    No 3,355 (41.6)  867 (20.8) 
Treatment duration (y) 
    ≥2 y 1,884 (45.1) 1.04 (0.97-1.12) 0.29 409 (20.1) 1.05 (0.85-1.30) 0.67 
    <2 y 1,386 (37.6)  434 (21.2) 
Recurrence 
    Yes 415 (45.8) 1.10 (1.01-1.2) 0.04 93 (21.7) 0.96 (0.70-1.32) 0.82 
    No 3,283 (40.9)  888 (21.3)  
Table 6.

Multivariable regression model of the association between neurobehavioral conditions with marital status, adjusted for age at last contact

CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis (y) 
    <13 3,338 (50.6) 1.44 (1.24-1.66) <0.0001 580 (20.5) 1.06 (0.9-1.24) 0.50 
    13-20 360 (15.4)  401 (22.7) 
Gender 
    Female 1,692 (38.5) 1.15 (1.09-1.22) <0.0001 524 (22) 0.93 (0.81-1.07) 0.31 
    Male 2,006 (44.2) 457 (20.7) 
Educational attainment 
    Did not complete high school 193 (50.4) 1.06 (0.92-1.22) 0.41 45 (31.7) 1.86 (1.34-2.59) 0.0002 
    Completed high school 2,139 (46.2) 1.11 (1.05-1.18) 0.0002 579 (26.8) 1.67 (1.45-1.91) <0.0001 
    College graduate 1,323 (34.4)  352 (15.5) 
Emotional distress (GSI T-score ≥50) 
    Yes 1613 (39.9) 1.03 (0.97-1.08) 0.39 544 (25.3) 1.33 (1.15-1.54) 0.0001 
    No 1,513 (36.8)  412 (18.0) 
NCQ: problems with task efficiency 
    Yes 935 (49.4) 1.27 (1.2-1.35) <0.0001 220 (25.4) 1.14 (0.97-1.35) 0.12 
    No 1,637 (35.6)  500 (18.5) 
NCQ: problems with organization 
    Yes 550 (44.4) 1.05 (0.98-1.12) 0.17 141 (22.7) 0.95 (0.8-1.14) 0.60 
    No 2,022 (38.5)  579 (19.7) 
NCQ: problems with memory 
    Yes 581 (43.5) 0.97 (0.91-1.04) 0.46 174 (25.9) 1.12 (0.94-1.33) 0.20 
    No 1,991 (38.6)  546 (18.9) 
NCQ: problems with emotional regulation 
    Yes 666 (41.8) 0.9 (0.85-0.97) 0.003 205 (24.6) 1.11 (0.95-1.31) 0.19 
    No 1,906 (38.9)  515 (18.9)  
CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis (y) 
    <13 3,338 (50.6) 1.44 (1.24-1.66) <0.0001 580 (20.5) 1.06 (0.9-1.24) 0.50 
    13-20 360 (15.4)  401 (22.7) 
Gender 
    Female 1,692 (38.5) 1.15 (1.09-1.22) <0.0001 524 (22) 0.93 (0.81-1.07) 0.31 
    Male 2,006 (44.2) 457 (20.7) 
Educational attainment 
    Did not complete high school 193 (50.4) 1.06 (0.92-1.22) 0.41 45 (31.7) 1.86 (1.34-2.59) 0.0002 
    Completed high school 2,139 (46.2) 1.11 (1.05-1.18) 0.0002 579 (26.8) 1.67 (1.45-1.91) <0.0001 
    College graduate 1,323 (34.4)  352 (15.5) 
Emotional distress (GSI T-score ≥50) 
    Yes 1613 (39.9) 1.03 (0.97-1.08) 0.39 544 (25.3) 1.33 (1.15-1.54) 0.0001 
    No 1,513 (36.8)  412 (18.0) 
NCQ: problems with task efficiency 
    Yes 935 (49.4) 1.27 (1.2-1.35) <0.0001 220 (25.4) 1.14 (0.97-1.35) 0.12 
    No 1,637 (35.6)  500 (18.5) 
NCQ: problems with organization 
    Yes 550 (44.4) 1.05 (0.98-1.12) 0.17 141 (22.7) 0.95 (0.8-1.14) 0.60 
    No 2,022 (38.5)  579 (19.7) 
NCQ: problems with memory 
    Yes 581 (43.5) 0.97 (0.91-1.04) 0.46 174 (25.9) 1.12 (0.94-1.33) 0.20 
    No 1,991 (38.6)  546 (18.9) 
NCQ: problems with emotional regulation 
    Yes 666 (41.8) 0.9 (0.85-0.97) 0.003 205 (24.6) 1.11 (0.95-1.31) 0.19 
    No 1,906 (38.9)  515 (18.9)  
Table 7.

Multivariable regression model of the association between physical conditions with marital status, adjusted for age at last contact

CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis (y) 
    <13 3,338 (50.6) 1.40 (1.21-1.62) <0.0001 580 (20.5) 1.08 (0.91-1.26) 0.38 
    13-20 360 (15.4)  401 (22.7) 
Gender 
    Female 1,692 (38.5) 1.20 (1.13-1.26) <0.0001 524 (22.0) 0.95 (0.83-1.09) 0.45 
    Male 2,006 (44.2)  457 (20.7) 
Educational attainment 
    Did not complete high school 193 (50.4) 1.10 (1.04-1.17) 0.0009 45 (31.7) 1.68 (1.46-1.93) <0.0001 
    Completed high school 2,139 (46.2)  579 (26.8) 
    College graduate 1,323 (34.4) 1.40 (1.21-1.62) <0.0001 352 (15.5) 1.08 (0.91-1.26) 0.38 
Short stature 
    Yes 978 (57.2) 1.27 (1.2-1.34) <0.0001 150 (23.7) 1.13 (0.94-1.36) 0.18 
    No 2,571 (37.0)  810 (20.9) 
Poor physical function (SF-36 T-score <40) 
    Yes 375 (42.9) 1.08 (1-1.18) 0.05 141 (31.7) 1.4 (1.18-1.67) 0.0001 
    No 2,717 (40.9)  687 (19.6)  
CharacteristicNever-marriedEver-divorced
n (%)RR (95% CI)Pn (%)RR (95% CI)P
Age at diagnosis (y) 
    <13 3,338 (50.6) 1.40 (1.21-1.62) <0.0001 580 (20.5) 1.08 (0.91-1.26) 0.38 
    13-20 360 (15.4)  401 (22.7) 
Gender 
    Female 1,692 (38.5) 1.20 (1.13-1.26) <0.0001 524 (22.0) 0.95 (0.83-1.09) 0.45 
    Male 2,006 (44.2)  457 (20.7) 
Educational attainment 
    Did not complete high school 193 (50.4) 1.10 (1.04-1.17) 0.0009 45 (31.7) 1.68 (1.46-1.93) <0.0001 
    Completed high school 2,139 (46.2)  579 (26.8) 
    College graduate 1,323 (34.4) 1.40 (1.21-1.62) <0.0001 352 (15.5) 1.08 (0.91-1.26) 0.38 
Short stature 
    Yes 978 (57.2) 1.27 (1.2-1.34) <0.0001 150 (23.7) 1.13 (0.94-1.36) 0.18 
    No 2,571 (37.0)  810 (20.9) 
Poor physical function (SF-36 T-score <40) 
    Yes 375 (42.9) 1.08 (1-1.18) 0.05 141 (31.7) 1.4 (1.18-1.67) 0.0001 
    No 2,717 (40.9)  687 (19.6)  

Male gender and younger age at diagnosis were consistently associated with greater likelihood of not getting married, in adjusted analyses. No differences were noted upon further stratification of the significant factors identified in multivariable analysis by gender or cranial radiation.

Table 8 and the Fig. 1 collectively present the results of the structural equation modeling. Table 8 provides a description of all significant variables and their contribution to the model, including the estimated regression coefficients (EST) for each parameter, the SE of the parameter estimates (SE), the coefficient divided by the SE (EST/SE, or z-score), the standardized coefficients (STDYX), and the P value for the path between the two variables. For binary dependent variables, the regression coefficients produced are logistic regression coefficients. Figure 1 represents a simplified graphic version of the complete SE results. A well fitting model (χ2 = 21.91; df = 14; P = 0.08; CFI = 0.999; TLI = 0.998; RMSEA = 0.009; WRMR = 0.557) explained 45.6% of the variance in survivors' never having been married. The strongest predictor of never having married, based on the weight of the standardized coefficients, was younger current age followed by short stature, poor task efficiency, male gender, history of CNS radiation, better memory, poor physical function, and poor emotional functioning.

Table 8.

Structural equation model for predictors of never-married status in CCSS cases (corresponding to Fig. 1)

Estimate (EST)Standard error (SE)EST/SESTD YX estimateP
Younger current age 0.091 0.003 28.06 0.518 <0.0001 
Short stature 0.225 0.035 6.34 0.198 <0.0001 
Poor task efficiency -0.047 0.007 -7.17 -0.154 <0.0001 
Male gender 0.233 0.035 6.62 0.090 <0.0001 
CNS radiation 0.219 0.045 4.83 0.079 <0.0001 
Better memory 0.046 0.011 4.06 0.078 <0.0001 
Poor physical function 0.004 0.001 4.63 0.074 <0.0001 
Poor emotional function 0.003 0.001 2.32 0.040 0.020 
Estimate (EST)Standard error (SE)EST/SESTD YX estimateP
Younger current age 0.091 0.003 28.06 0.518 <0.0001 
Short stature 0.225 0.035 6.34 0.198 <0.0001 
Poor task efficiency -0.047 0.007 -7.17 -0.154 <0.0001 
Male gender 0.233 0.035 6.62 0.090 <0.0001 
CNS radiation 0.219 0.045 4.83 0.079 <0.0001 
Better memory 0.046 0.011 4.06 0.078 <0.0001 
Poor physical function 0.004 0.001 4.63 0.074 <0.0001 
Poor emotional function 0.003 0.001 2.32 0.040 0.020 
Figure 1.

Graphic representation of structural equation modeling of predictors of never-married status in CCSS cases.

Figure 1.

Graphic representation of structural equation modeling of predictors of never-married status in CCSS cases.

Close modal

History of CNS radiation was an indirect influence on never having married through (a) short stature (P = <0.0001), (b) poor memory (P = <0.0001), (c) poor physical function (P = <0.0001); and (d) poor task efficiency (P = <0.001). History of CNS radiation also was a direct influence on never having married, presumably through factors that we did not measure in this study. Short stature was an indirect influence on never having married through poor task efficiency (P = <0.0001) and poor physical function (P = <0.0001). The indirect impact of poor task efficiency on never having married was through by poor memory; the indirect impact of poor physical function was through by poor task efficiency.

Predictors of Ever-Divorced Status in Survivors

Among ever-married survivors, after adjusting for gender and age at last contact, factors found to be significantly associated with history of divorce were poor physical functioning (RR, 1.52; 95% CI, 1.30-1.78), perceived fertility problem (RR, 1.14; 95% CI, 1.01-1.27), emotional distress (RR, 1.40; 95% CI, 1.25-1.57), problems with task efficiency (RR, 1.37; 95% CI, 1.20-1.58), impaired working memory (RR, 1.34; 95% CI, 1.16-1.56), and problems with emotional regulation (RR, 1.32; 95% CI, 1.15-1.52) as shown in Table 4. No significant treatment factor was identified. Multivariable models were examined for divorce (Tables 5 to 7). An age younger than 13 years at diagnosis (RR, 1.28: 95% CI, 1.03-1.60), emotional distress (RR, 1.33; 95% CI, 1.15-1.54), and self-report of poor physical functioning (RR, 1.40; 95% CI, 1.18-1.67) were independently predictive of divorce. Interactions were examined; there were no differences in the association between risk factors and divorce status between males and females and by cranial radiation status.

In this large, multisite cohort of adult survivors of childhood cancer, we concluded that survivors were 1.21 times more likely to be unmarried than the sibling comparison group and 1.25 times more likely to be unmarried than the U.S. Census population, after adjusting for age, gender, and race. Our risk estimates are similar to that of the 2007 report by Frobisher et al. based on the 9,954-member British Cancer Survivor Study (BCCSS; ref. 30). Younger age at diagnosis and history of cranial radiation were the most important predictors of never getting married among cases. From structural equation modeling, we found that cranial radiation exposure was an indirect influence on never having married through short stature, impaired memory, worse processing speed, and poor physical function. Emotional distress among survivors was a direct influence on never getting married, separate from cranial radiation exposure. Our other major finding was that divorce patterns among childhood cancer survivors were similar to that of the general population and a sibling comparison group. This reassuring conclusion is contrary to an older report by Byrne et al. in 1989 (24). Ours is the largest study to our knowledge that examines divorce outcomes.

Our results should be further compared and contrasted with that of the other large, recent cohort study by Frobisher et al. in the BCSS. The BCCSS study only compared cases with population data and no summary relative risk statistic was reported. However, marriage frequencies stratified by age and gender from the Frobisher publication suggested that survivors were 1.1 to 1.6 times more likely to be unmarried. These estimates are similar to our own verified with both sibling and general population comparison groups. Both the CCSS and the BCCSS studies identified males, history of CNS tumor, exposure to CNS radiation, and poor physical function as predictors of nonmarriage.

Our CCSS study of marriage was unique in that we also included standardized measures specific to emotional and cognitive functioning to understand why certain patient groups were less likely to marry. In the CCSS cohort, structural equation modeling helped to elucidate that cranial radiation indirectly influenced never getting married through worse cognitive processing difficulties and short stature, as well as poor physical function. In the childhood cancer survivor population, short stature is usually due to decreased pituitary function as a result of CNS radiation. In the general population, diminished height is known to be associated with lower marriage rates (44), and bachelors are significantly shorter (45). In 1996, a meta-analytic review concluded that females are more romantically attracted to taller males (46). In a more recent large study of responses to personal advertisements, males with higher education and taller height had significantly more responses (47). Pawlowski speculates that “male height is an important trait on the mate market” because it is an indicator of reproductive potential, whereas education and intelligence are proxies for economic status (47). There is evidence that taller males father more children (45) and are perceived as healthier (48).

Structural equation analysis suggests that cranial radiation also has a direct influence on nonmarriage, presumably mediated through some factor that we did not measure in this study. Future studies should examine the potential role of factors such as social intelligence, attractiveness to the other sex, altered sexual maturation, and libido. Emotional distress and male gender were other factors directly associated with never getting married.

Cranial radiation has been associated with social difficulties in past studies. Pui et al. found cranial radiation to predict nonmarriage in female survivors of acute lymphoblastic leukemia (49). In a study of adolescent survivors, Barrera et al. concluded that those treated with cranial radiation were less likely to have close friends than survivors treated without cranial radiation (50). Thus, it seems that the negative effects of cranial radiation on social integration begin at an early age and persist into adulthood.

The current study has some methodological characteristics that should be considered in the interpretation of the results. Due to the time elapsed between surveys and the nature of the question about marital status, it is possible that some cases of divorce were missed. As a result, we may have underestimated the risk of being ever-divorced. The CCSS participants were diagnosed between 1970 and 1986 in an earlier era, and thus may not be directly generalizable to more recently treated cohorts of pediatric cancer survivors. Finally, although the size of the CCSS cohort is a strength, it also limits the nature of contact with participants to standardized questionnaires. Thus, although we can state that survivors marry less frequently than controls of similar age and gender, we do not have data directly relating to the thoughts, desires, and motivations underlying this behavior.

The CCSS is a valuable resource for survivorship studies because of the multisite design, large sample size, and high participation rates (51). For the baseline CCSS survey, 69% of the total eligible population participated (15% could not be located and 15% declined participation). Participation rates on the follow-up surveys have ranged from 77% to 81%. Comparisons of available demographic and cancer-related characteristics between participants and nonparticipants at the initial baseline questionnaire showed that the only significant difference between these groups was vital status. That is, the next-of-kin relatives of patients who died more than 5 years after diagnosis were less likely to have participated than patients who were still alive. Comparisons have also been made between participants and nonparticipants at subsequent questionnaires (52). Although differences are moderate in size (<10% differences), the study retains more female, white race, college-educated, higher-income, and older participants. In our current analysis, we adjust for gender, race, age, and socioeconomic status.

Marriage and divorce patterns are objective measures that can be used to gauge social integration and success of intimate relationships among childhood cancer survivors. Although it can be debated whether marriage is a desirable outcome, marriage is generally an expected developmental goal in our society to the extent that most adults in the United States are married by the age of 30 years. Our large cohort study confirms that childhood cancer survivors are less likely to be married compared with their noncancer peers. Among survivors, patients with CNS tumors or a history of cranial radiation were most likely not to marry. Cranial radiation influenced marriage status through short stature, cognitive processing difficulties, and poor physical function. Except for those with reduced physical function, there was no increased risk of divorce among survivors who did marry. Studies such as ours are important to understanding how the growing population of childhood cancer survivors functions in our society. Separate analyses are underway in the CCSS to better understand factors that contribute to other adult benchmarks such as living independently, achieving higher education, and personal income.

No potential conflicts of interest were disclosed.

The Childhood Cancer Survivor Study (CCSS) is a collaborative, multi-institutional project, funded as a resource by the National Cancer Institute, of individuals who survived five or more years after diagnosis of childhood cancer.

CCSS is a retrospectively ascertained cohort of 20,346 childhood cancer survivors diagnosed before age 21 between 1970 and 1986 and approximately 4,000 siblings of survivors, who serve as a control group. The cohort was assembled through the efforts of 26 participating clinical research centers in the United States and Canada. The study is currently funded by a U24 resource grant (NCI grant # U24 CA55727) awarded to St. Jude Children's Research Hospital. Currently, we are in the process of expanding the cohort to include an additional 14,000 childhood cancer survivors diagnosed before age 21 between 1987 and 1999. For information on how to access and utilize the CCSS resource, visit www.stjude.org/ccss.

St. Jude Children's Research Hospital, Memphis, TN 
Children's Healthcare of Atlanta/Emory University Atlanta, GA 
Children's Hospitals and Clinics of Minnesota Minneapolis St. Paul, MN 
Children's Hospital and Medical Center, Seattle, WA 
Children's Hospital, Denver, CO 
Children's Hospital Los Angeles, CA 
Children's Hospital, Oklahoma City, OK 
Children's Hospital of Philadelphia, PA 
Children's Hospital of Pittsburgh, PA 
Children's National Medical Center, Washington, DC 
Cincinnati Children's Hospital Medical Center 
City of Hope-Los Angeles, CA 
Dana-Farber Cancer Institute/Children's Hospital Boston, MA 
Fred Hutchinson Cancer Research Center, Seattle, WA 
Hospital for Sick Children, Toronto, ON 
International Epidemiology Institute, Rockville, MD 
Mayo Clinic, Rochester, MN 
Memorial Sloan-Kettering Cancer Center New York 
Miller Children's Hospital 
National Cancer Institute, Bethesda, MD 
Nationwide Children's Hospital, Columbus, Ohio 
Riley Hospital for Children, Indianapolis, IN 
Roswell Park Cancer Institute, Buffalo, NY 
St. Louis Children's Hospital, MO 
Stanford University School of Medicine, Stanford, CA 
Texas Children's Hospital, Houston, TX 
University of Alabama, Birmingham, AL 
University of Alberta, Edmonton, AB 
University of California-Los Angeles, CA 
University of California-San Francisco, CA 
University of Michigan, Ann Arbor, MI 
University of Minnesota, Minneapolis, MN 
University of Southern California 
UT-Southwestern Medical Center at Dallas, TX  
U.T.M.D. Anderson Cancer Center, Houston, TX 
*Institutional Principal Investigator 
Former Institutional Principal Investigator 
Leslie L. Robison, Ph.D.#‡, Melissa Hudson, M.D.* 
Greg Armstrong, M.D., Daniel M. Green, M.D. 
Lillian Meacham, M.D.*, Ann Mertens, Ph.D. 
Joanna Perkins, M.D.* 
Douglas Hawkins, M.D.*, Eric Chow, M.D. 
Brian Greffe, M.D.* 
Kathy Ruccione, RN, MPH* 
John Mulvihill, M.D. 
Jill Ginsberg, M.D.*, Anna Meadows, M.D. 
Jean Tersak, M.D.* 
Gregory Reaman, M.D.*, Roger Packer, M.D. 
Stella Davies, M.D., Ph.D. 
Smita Bhatia, M.D.* 
Lisa Diller, M.D.* 
Wendy Leisenring, Sc.D.* 
Mark Greenberg, MBChB.*, Paul C. Nathan, M.D.* 
John Boice, Sc.D. 
Vilmarie Rodriguez, M.D.* 
Charles Sklar, M.D.*, Kevin Oeffinger, M.D. 
Jerry Finklestein, MD 
Roy Wu, Ph.D., Nita Sibel, M.D. 
Preetha Rajaraman, Ph.D. 
Amanda Termuhlen, M.D.*, Sue Hammond, M.D. 
Terry A. Vik, M.D.* 
Martin Brecher, M.D.* 
Robert Hayashi, M.D.* 
Neyssa Marina, M.D.*, Sarah S. Donaldson, M.D. 
Zoann Dreyer, M.D.* 
Kimberly Whelan, M.D., MSPH* 
Yutaka Yasui, Ph.D. 
Jacqueline Casillas, MD MSHS*, Lonnie Zeltzer, M.D.†‡ 
Robert Goldsby, M.D.* 
Raymond Hutchinson, M.D.* 
Joseph Neglia, M.D., MPH
Dennis Deapen, Dr. P.H. 
Dan Bowers, M.D.* 
Louise Strong, M.D.*, Marilyn Stovall, MPH, Ph.D. 
Member CCSS Steering Committee 
#Project Principal Investigator (U24 CA55727) 
St. Jude Children's Research Hospital, Memphis, TN 
Children's Healthcare of Atlanta/Emory University Atlanta, GA 
Children's Hospitals and Clinics of Minnesota Minneapolis St. Paul, MN 
Children's Hospital and Medical Center, Seattle, WA 
Children's Hospital, Denver, CO 
Children's Hospital Los Angeles, CA 
Children's Hospital, Oklahoma City, OK 
Children's Hospital of Philadelphia, PA 
Children's Hospital of Pittsburgh, PA 
Children's National Medical Center, Washington, DC 
Cincinnati Children's Hospital Medical Center 
City of Hope-Los Angeles, CA 
Dana-Farber Cancer Institute/Children's Hospital Boston, MA 
Fred Hutchinson Cancer Research Center, Seattle, WA 
Hospital for Sick Children, Toronto, ON 
International Epidemiology Institute, Rockville, MD 
Mayo Clinic, Rochester, MN 
Memorial Sloan-Kettering Cancer Center New York 
Miller Children's Hospital 
National Cancer Institute, Bethesda, MD 
Nationwide Children's Hospital, Columbus, Ohio 
Riley Hospital for Children, Indianapolis, IN 
Roswell Park Cancer Institute, Buffalo, NY 
St. Louis Children's Hospital, MO 
Stanford University School of Medicine, Stanford, CA 
Texas Children's Hospital, Houston, TX 
University of Alabama, Birmingham, AL 
University of Alberta, Edmonton, AB 
University of California-Los Angeles, CA 
University of California-San Francisco, CA 
University of Michigan, Ann Arbor, MI 
University of Minnesota, Minneapolis, MN 
University of Southern California 
UT-Southwestern Medical Center at Dallas, TX  
U.T.M.D. Anderson Cancer Center, Houston, TX 
*Institutional Principal Investigator 
Former Institutional Principal Investigator 
Leslie L. Robison, Ph.D.#‡, Melissa Hudson, M.D.* 
Greg Armstrong, M.D., Daniel M. Green, M.D. 
Lillian Meacham, M.D.*, Ann Mertens, Ph.D. 
Joanna Perkins, M.D.* 
Douglas Hawkins, M.D.*, Eric Chow, M.D. 
Brian Greffe, M.D.* 
Kathy Ruccione, RN, MPH* 
John Mulvihill, M.D. 
Jill Ginsberg, M.D.*, Anna Meadows, M.D. 
Jean Tersak, M.D.* 
Gregory Reaman, M.D.*, Roger Packer, M.D. 
Stella Davies, M.D., Ph.D. 
Smita Bhatia, M.D.* 
Lisa Diller, M.D.* 
Wendy Leisenring, Sc.D.* 
Mark Greenberg, MBChB.*, Paul C. Nathan, M.D.* 
John Boice, Sc.D. 
Vilmarie Rodriguez, M.D.* 
Charles Sklar, M.D.*, Kevin Oeffinger, M.D. 
Jerry Finklestein, MD 
Roy Wu, Ph.D., Nita Sibel, M.D. 
Preetha Rajaraman, Ph.D. 
Amanda Termuhlen, M.D.*, Sue Hammond, M.D. 
Terry A. Vik, M.D.* 
Martin Brecher, M.D.* 
Robert Hayashi, M.D.* 
Neyssa Marina, M.D.*, Sarah S. Donaldson, M.D. 
Zoann Dreyer, M.D.* 
Kimberly Whelan, M.D., MSPH* 
Yutaka Yasui, Ph.D. 
Jacqueline Casillas, MD MSHS*, Lonnie Zeltzer, M.D.†‡ 
Robert Goldsby, M.D.* 
Raymond Hutchinson, M.D.* 
Joseph Neglia, M.D., MPH
Dennis Deapen, Dr. P.H. 
Dan Bowers, M.D.* 
Louise Strong, M.D.*, Marilyn Stovall, MPH, Ph.D. 
Member CCSS Steering Committee 
#Project Principal Investigator (U24 CA55727) 

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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