Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort

Objectives

Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women.

Study design

We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13–55 who delivered 1964–1976, with Israel’s National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1–4 (n = 19,703), adjusting for reproductive and demographic variables.

Results

Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HR_adj) = 0.62, 95 % confidence interval (CI) 0.54–0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HR_adj = 1.69, CI 1.39–2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HR_adj = 2.48, CI 1.22–5.03).

Conclusion

Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.

     

Birth weight and other risk factors for acute leukemia in the Jerusalem Perinatal Study cohort.

OBJECTIVES: To assess the effect of birth weight of children and their siblings and other perinatal/parental factors on the risk of acute leukemia. METHODS: We linked data from the Jerusalem Perinatal Study, a population-based research cohort (n = 88,829) of offspring born 1964 to 1976, with Israel's Cancer Registry. Risk factors for acute leukemia were assessed using univariate and multivariate proportional hazards models. RESULTS: Leukemias developed in 65 individuals [24 acute myeloid leukemias (AML) and 41 acute lymphoblastic leukemias (ALL)]. A positive linear relation was found between gender-adjusted birth weight and all leukemias [hazard ratio (HR) 1.85, 95% confidence interval (95% CI) 1.1-3.0] and AML (HR 2.9, 95% CI 1.3-6.4). The association between birth weight and AML was especially notable among infants (HR 8.14, 95% CI 1.8-38.9 for age 0 to 1 year) but was also observed among subjects ages >14 years at diagnosis. The relation was particularly strong among females (P = 0.001). Other risk factors for AML risk on univariate analysis were maternal origin, socioeconomic status, birth weight of sibling > 3,500 g, and family size. On multivariate analysis, only birth weight retained borderline significance (adjusted HR 2.38 per kg, 95% CI 1.0-5.7). Significant predictors for ALL in both univariate and multivariate analyses were male sex (adjusted HR 1.92, 95% CI 1.0-3.7) and birth weight categories > or = 3,000 g introduced into the model as nonlinear terms. CONCLUSION: Birth weight is associated with an increased risk of acute leukemia in infants, children, and young adults. Perinatal factors play a role in the development of childhood leukemias, but the patterns of association vary by leukemia type.     

Gestational diabetes and the risk of breast cancer among women in the Jerusalem Perinatal Study

Gestational diabetes is becoming increasingly common; it is important to determine how it relates to future risk of disease. We investigated the relation of gestational diabetes to breast cancer in 37,926 women who had one or more live births in 1964–1976 for whom information had been collected on complications of pregnancy. In this cohort there were 1,626 cases of breast cancer reported to the Israel Cancer Registry before January 1, 2005 and 410 cases of gestational diabetes recorded from birth records. There were 29 cases of breast cancer among women diagnosed with gestational diabetes. Using Cox proportional hazards models to control for age and birth order at the first observed birth and other characteristics, we found that the incidence of breast cancer was increased among women diagnosed with gestational diabetes (relative rate = 1.5, 95% confidence interval 1.0–2.1). This effect was seen only among women 50 years and older (relative rate 1.7, 95% confidence interval 1.1–2.5) but not among women <50 (relative rate = 1.0, 95% confidence interval 0.5–2.1). The findings suggest that gestational diabetes may be an important early marker of breast cancer risk among post-menopausal women, but these results need to be confirmed in future studies.     

Increased cancer risk in offspring of women with colorectal carcinoma: a Swedish register-based cohort study

BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background. METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference. RESULTS: A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population. CONCLUSIONS: This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.     

Survival of male breast cancer patients: Population-based cohort study

Little information is available on the survival of male breast cancer patients because the disease is extremely rare in men. Moreover, previous reports on the prognosis of male breast cancer have been conflicting. We took advantage of a number of large, nationwide registries in Sweden to evaluate the prognostic value of sex in breast cancer patients. A population-based cohort of 269 male and 30 011 female breast cancer patients born after 1935 and diagnosed with primary breast cancer between 1970 and 1997 was generated by linking a number of Swedish registries, including the Swedish Cancer Registry, the Cause of Death Registry, the Swedish Generation Registry, and the Registry of Population and Population Changes. We used this cohort to quantify the association between the sex of the patient and breast cancer-specific mortality, using the Cox proportional hazards. The sex of the patient did not significantly influence the prognosis of breast cancer. Adjusting for age at diagnosis and calendar period did not alter the results. Nor did the results change when the analyses were repeated for all causes of morality. Our study, one of the largest to date, failed to find evidence to support the proposed association between the sex of breast cancer patients and survival. Given the previous reports, which advocated that male breast cancer patients have poorer survival and need aggressive treatment strategies, our findings are reassuring and clinically very important. ( Cancer Sci 2009; 100: 292–295)     

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

One in five cancers in women is diagnosed prior to and during a woman's fertile years. Our study evaluates mortality risks in offspring of mothers with history of cancer. From the Swedish Multi‐generation Register and the Cancer Register, we identified all 174,893 children whose mother had been diagnosed with cancer between 1958 and 2001. We categorized offspring into those born before (>1 year before), around (within 1 year before and after diagnosis) and after (>1 year after) their mother's cancer diagnosis and compared their risks of death (standardized mortality ratios, SMRs) and causes of death to the background population. Overall, offspring of mothers diagnosed with cancer had no increased mortality risk (SMR, 1.00; 95% confidence interval [CI], 0.97–1.03). Increased mortality risks were found in offspring of mothers with tobacco‐related cancers (head and neck, thoracic and cervical) (SMR, 1.23; 95% CI, 1.13–1.33), in children born around their mother's diagnosis (SMR, 1.66; 95% CI, 1.25–2.13) and in children born after their mother's hematopoietic cancer diagnosis (SMR, 2.07; 95% CI, 1.10–3.35). Compared to the background population, children born around their mother's diagnosis were more likely to die of congenital and perinatal conditions. Overall, offspring of women diagnosed with cancer were not at increased risk of death, except for certain subgroups. Timing of pregnancy in relation to diagnosis and cancer site modifies mortality risks in the offspring.     

Antenatal maternal bereavement and childhood cancer in the offspring: a population-based cohort study in 6 million children

Background:

Prenatal stress may increase the susceptibility to childhood cancer by affecting immune responses and hormonal balance. We examined whether antenatal stress following maternal bereavement increased the risk of childhood cancer.

Methods:

All children born in Denmark from 1968 to 2007 (N=2 743 560) and in Sweden from 1973 to 2006 (N=3 400 212) were included in this study. We compared cancer risks in children born to women who lost a first-degree relative (a child, spouse, a parent, or a sibling) the year before pregnancy or during pregnancy with cancer risks in children of women who did not experience such bereavement.

Results:

A total of 9795 childhood cancer cases were observed during follow-up of 68 360 707 person years. Children born to women who lost a child or a spouse, but not those who lost other relatives, had an average 30% increased risk of any cancer (hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.96–1.77). The HRs were the highest for non-Hodgkin disease (512 cases in total, HR 3.40, 95% CI 1.51–7.65), hepatic cancer (125 cases in total, HR 5.51, 95% CI 1.34–22.64), and testicular cancer (86 cases in total, HR 8.52, 95% CI 2.03–37.73).

Conclusion:

Our data suggest that severe antenatal stress following maternal bereavement, especially due to loss of a child or a spouse, is associated with an increased risk of certain childhood cancers in the offspring, such as hepatic cancer and non-Hodgkin disease, but not with childhood cancer in general.     

Prostate cancer screening in high-risk men: African American Hereditary Prostate Cancer Study Network

BACKGROUND: There are scant data available on prostate cancer screening among high-risk African American men with positive family histories. It is important to determine whether or not their screening rates differ from those in the general population. METHODS: This study computed rates of previous digital rectal examination (DRE) and prostate-specific antigen (PSA) screening for prostate cancer in cancer-free (unaffected) relatives age 40-69 years from African American families that had four or more men with prostate cancer. The rates for these 134 high-risk African American men from the African American Hereditary Prostate Cancer Study (AAHPC) were compared with nationwide estimates obtained from participants in the 1998 and 2000 National Health Interview Survey (NHIS), for which the numbers of demographically comparable subjects were 5583 (4900 Caucasians, plus 683 African Americans) and 3359 (2948 Caucasians, 411 African Americans), respectively. RESULTS: Men in the AAHPC cohort (with a strong positive family history) had significantly less screening than both African Americans and Caucasians in the NHIS cohorts. Only about one-third (35%) of the men in the AAHPC unaffected cohort had ever had a DRE, and only about 45% of them had ever received a PSA test. These rates were much lower than those obtained for African American men in the NHIS: 45% for DRE and 65% for PSA. These discrepancies increased with age. CONCLUSIONS: Older African American men with positive family histories report surprisingly low rates of DRE and PSA screening compared with their counterparts in the NHIS surveys. At-risk men need to be informed of the benefits and limitations of prostate cancer screening and actively involved in decision-making for or against prostate cancer screening.     

Prostate cancer specific mortality in the Florence screening pilot study cohort 1992-1993

The impact of screening on prostate cancer mortality is still unknown. A favourable impact is suggested by uncontrolled and possibly biased studies. Mortality from all causes and from prostate cancer was assessed in a cohort of 6,861 males aged 60-74 years, participants to a pilot screening study during 1991-1994. Observed/expected mortality was determined by linkage with cancer and mortality registries. Prostate cancer standardised mortality rate (SMR) in the overall series (751 subjects excluded by GPs for disabling illness or prostate cancer; 3,448 refusers, 2,662 attenders; 67,321.2 men-year) was 0.96 (95% confidence interval (CI)=0.74-1.22) when deaths from prevalent cancers diagnosed before screening were considered. Reduced prostate cancer mortality (SMR=0.48; 95% CI=0.26-0.83), persisting beyond five years after study entry (SMR=0.48; 95% CI=0.22-0.90), was observed in attenders and not in refusers (SMR=0.99; 95% CI=0.69-1.37). This finding might suggest a screening effect, but might also be ascribed to an healthy screening effect, and cannot be assumed as a reliable evidence of screening efficacy.     

Dietary supplement use patterns in men with prostate cancer: the Cancer Prostate Sweden Study

BackgroundIn a European setting, we know little about the use of dietary supplements among men with prostate cancer (PCa) and to what extent lifestyle, disease or other factors influence such use.Patients and methodsWe evaluated supplement use in 1127 men with incident PCa and in 900 population controls in Sweden. Age-adjusted binary regression with an identity link was carried out to estimate prevalence differences and corresponding 95% confidence intervals (CIs). Modifying effects of lifestyle- and diet-related factors were explored by statistical assessment of additive interaction.ResultsAmong men with PCa, 542 individuals (48%) had used supplements, which was a 10% (95% CI: 5.9%–15%) higher prevalence than among population controls. Among individuals with high intake of fatty fish, vegetables, and phytoestrogens, but low intake of saturated fat, supplement use was 29% (95% CI: 18%–41%) more common in men with PCa than in population controls. We found no evidence of heterogeneity by categories of education, smoking history, body mass index, fiber, fruit, or phytoestrogen intake, treatment, or disease stage.ConclusionSupplement use is common in Swedish men with PCa, especially among those with a healthy dietary pattern.     

Tobacco use and cancer survival: A cohort study of 40,230 Swedish male construction workers with incident cancer

On theoretical grounds, nicotine has been implicated as a modifier of cancer progression. We investigated possible associations of smoking or use of Scandinavian moist snuff (snus) with survival after cancer among Swedish male construction workers. Snus use is associated with substantial exposure to nicotine but not to the combustion products in smoke. Among 336,381 workers with detailed information on tobacco use in 1971–1992, we observed 40,230 incident cancers. Complete follow‐up through 2007 was accomplished through linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) for death from any cause, cancer‐specific death and death from other causes were derived from Cox proportional hazards regression models adjusted for age at diagnosis, body mass index at study entry and period of diagnosis. Never users of any tobacco served as reference. Increased risks of cancer‐specific death were observed both among exclusive smokers (HR_{all cancer} 1.15, 95% CI: 1.10–1.21) and never‐smoking snus users (1.15, 95% CI: 1.05–1.26). As regards deaths due to other causes, exclusive smokers had higher relative risks than exclusive snus users (p = 0.03). A history of tobacco use, even exclusive use of the seemingly benign snus, is associated with moderately increased cancer‐specific mortality. Although nicotine might play a role, the mechanisms warrant further investigation.     

The interval between cancer diagnosis among mothers and offspring in a population-based cohort

Background Familial cancers may be due to shared genes or environment, or chance aggregation. We explored the possibility that ascertainment bias influences cancer detection in families, bearing upon the time interval between diagnosis of affected mothers and offspring. Methods The Jerusalem Perinatal Study (JPS) comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 –1976 and their offspring (n = 88,829). After linking identification numbers with Israel’s Cancer Registry we measured the absolute time interval between initial cancer diagnoses in affected mother-offspring pairs. We tested the probability of obtaining intervals as short as those observed by chance alone, using a permutation test on the median interval. Results By June 2003 cancer had developed in 105 mother-offspring pairs within the cohort. Common sites among mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and cervix (7%), while for offspring in affected pairs common cancers were leukemia (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The median interval between diagnoses was 5.9 years, but for 33% of affected pairs the interval was ≤3 years. The probability of this occurring by chance alone was 0.03. This held true whether the offspring’s or mother’s diagnosis was first (P < 0.01). Conclusions In a population-based cohort followed for three decades, the absolute interval between the diagnosis of cancer in mothers and their offspring is shorter than expected by chance. Explanations include shared environmental exposures or the possibility that cancer ascertainment in one pair member affects health behaviors in the other resulting in early diagnosis. The latter may bias the estimation of anticipation and survival in familial cancers. Supported by Grant RO1-CA-80197 from the National Institutes of Health (NIH)     

Advanced paternal age and childhood cancer in offspring: A nationwide register‐based cohort study

Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood cancer in offspring in a large nationwide cohort of 1,904,363 children born in Denmark from 1978 through 2010. The children were identified in the Danish Medical Birth Registry and were linked to information from other national registers, including the Danish Cancer Registry. In total, 3,492 children were diagnosed with cancer before the age of 15 years. The adjusted hazard ratio of childhood cancer according to paternal age was estimated using Cox proportional hazards regressions. We found a 13% (95% confidence interval: 4–23%) higher hazard rate for every 5 years advantage in paternal age for acute lymphoblastic leukemia, while no clear association was found for acute myeloid leukemia (hazard ratio pr. 5 years = 1.02, 95% confidence interval: 0.80–1.30). The estimates for neoplasms in the central nervous system suggested a lower hazard rate with higher paternal age (hazard ratio pr. 5 years = 0.92, 95% confidence interval: 0.84–1.01). No clear associations were found for the remaining childhood cancer types. The findings suggest that paternal age is moderately associated with a higher rate of childhood acute lymphoblastic leukemia, but not acute myeloid leukemia, in offspring, while no firm conclusions could be made for other specific cancer types.     

Cancer in the offspring of parents with lung cancer

Despite several studies on the role of passive smoking in the development of childhood cancer, particularly leukaemia, lymphomas and brain cancer, no definitive answer has yet been provided. The aim of the cohort study reported here was to analyse the incidence of cancer in the offspring of young lung cancer patients on the basis of the assumption that all of the offspring were exposed passively to smoke. The files of the Danish Cancer Registry provided 3348 cases of lung cancer patients born after 1935, and their offspring (n = 6417) were identified through the Danish Population Register. The files of the offspring were then linked with the files of the Danish Cancer Registry and the numbers of cancers observed in the offspring were compared with those expected from national age-specific and calender-time-specific rates. A total of 135 333 person-years was the basis for analysis. Twenty-six cancers were observed, with 30.3 expected, yielding a standardised incidence ratio (SIR) of 0.9 (90% confidence interval (CI), 0.6–1.2). There was no excess of brain tumours, leukaemias or lymphomas. Stratification for sex of the lung cancer patients revealed a non-significantly increased risk for both non-Hodgkin’s lymphoma (three cases; SIR = 3.4; 90% CI: 0.9–8.7) and Hodgkin’s disease (three cases; SIR = 2.6; 90% CI: 0.7–6.6) in the offspring of female lung cancer patients. These results suggest that there is little evidence of an excess cancer risk in childhood, whether due to passive smoking or to as yet unidentified genetic factors, among the offspring of people who develop lung cancer. However, the results are limited by the fact that exposure was only assessed indirectly, with no measurement of actual cigarette consumption made.