The population impact of familial cancer, a major cause of cancer

Abstract

The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant cancers among spouses. Almost all cancers showed a significant familial risk. The highest PAFs were found for the common cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96% for the invasive and in situ cancers in the FDRs and SDRs. The cancers between spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among spouses was higher than the familial risk. Our study shows that the overall familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.Twin data suggest that cancer is an environmental disease with a significant genetic component. 1 The population attributable fraction (PAF) is an epidemiological measure that estimates the population impact of various risk factors to the etiology of a disease. The PAF depends on the magnitude of the effect and the size of the exposed population. 2 The PAF has been traditionally used to assess modifiable environmental risk factors, but it has also been increasingly used in disease genetics to gain an understanding of the population impact of identified gene variants. 3,4 A recent PAF estimate concerning lifestyle and environmental factors on all cancer types in the British population ranked tobacco first (19.4%), followed by unhealthy diet (9.2%), overweight and obesity (5.5%), alcohol use (4.0%) and occupation (3.5%). 5 Increased cancer incidence among family members is most likely due to having more shared genes than the population at large, but family members also share habits and lifestyle more than the general population. However, the main argument that the familial clustering of most cancers is largely a result of genetics is the generally low spousal correlation for cancer risk after long cohabitation. 6 Even if familial cancer has a main genetic component, the risk may be modifiable through genetic counseling and management. Family history is a risk factor for which advice and management may bring medical benefits. 7 Many cancer screening...

Increased risk of hip fracture among spouses—evidence of a homogamy effect

“…Family history is a strong risk factor for hip fracture [7]. The effect of parental history of diseases for the risk of disease in first-degree relatives has been assumed to be mainly related to genetic factors [7, 23]. In a study of women and men from seven prospectively studied cohorts, a total of 34,928 women and men, 6 % reported a maternal history of hip fracture.…”

“…There is an obvious heredity both for variation in bone density and for fractures [7]. However, parents and children also share the same socioeconomic conditions and environmental factors which might have effects on disease risk [23]. On the other hand, the socioeconomic and environmental circumstances are even more likely to be similar in older married couples who have lived together for a more extended time period compared to parents and children.…”

“…However, SIR for oesophagus cancer was approximately 3.0 in spouses and 2.64 in first-degree relatives. The population attributable fraction for familial cancer was estimated to 6 % [23]. Genetic factors and lifestyle factors often occur together.…”

Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations

“…23–25 The main limitation was the lack of information on tumor characteristics and on covariates that affect the risk of a prostate cancer diagnosis, such as family history of prostate cancer 26 and socioeconomic status. 27 …”

Occupational exposure to pesticides and prostate cancer: a systematic review and meta-analysis

“…In spite of the documented increased risk of PC among those with a positive family history,89 90 very few studies adjusted for this important confounder. We obtained a high and significant pooled OR from pooling the results of three studies43 47 54 that estimated PC risk among the highest pesticide exposed groups that have a positive family history.…”