Cancer can also show increased incidence in families without a clear- cut mendelian pattern of inheritance. It is estimated that as many as 20% of all breast cancers occurring in families that lack a clear, highly penetrant mendelian disorder nonetheless have a significant genetic contribution, as revealed by twin and family studies. The observed increase in cancer risk when relatives are affected may be due to pathogenic variants in a single gene but with penetrance that is sufficiently reduced to obscure any mendelian inheritance pattern. For example, pathogenic variants PALB2 can increase lifetime risk for breast cancer to ~25% by age 55 and ~40% by age 85. A lack of increased breast cancer risk in men with PALB2 pathogenic variants further obscures the inheritance pattern, although there is a significantly increased risk for pancreatic cancer. Germline pathogenic variants in BRIP1 and RAD51C have simi lar effects in the setting of ovarian cancer.

The bulk of familial cancer is, however, likely to have a complex etiology caused by both genetic and shared environmental factors. The degree of complex familial cancer risk can be assessed by epidemiologic studies that compare how often the disease occurs in relatives versus the general population. The age- specific incidence of many forms of cancer in family members of probands is increased over the incidence of the same cancer in an age- matched cohort in the general population (Fig. 1). This increased risk has been observed in individuals whose first- degree relatives (parent, sibling, or child) are affected by a wide variety of different cancers, with an even greater increase in incidence when two first- degree relatives are affected. For example, population- based epidemiologic studies have shown that ~5% of all individuals in North America and Western Europe will develop colorectal cancer in their lifetime, but the lifetime risk is increased two- to threefold if one first- degree relative is affected.

Fig1. Standardized incidence ratios (SIRs) for cancers at various sites in first- degree relatives (parent, sibling, or child) of an affected person. SIR is similar to the relative risk ratio (λr ) based on prevalence of disease, except SIR is the ratio of the incidence of cases of cancer in relatives divided by the number expected from the incidence in age- matched controls. Error bars reflect 95% confidence limits on the SIRs. (Adapted from Hemminki K, Sundquist J, Lorenzo Bermejo J: Familial risks for cancer as the basis for evidence- based clinical referral and counseling, Oncologist 13:239– 247, 2008.)

In agreement with the frequently complex inheritance of cancer risk, genome- wide association studies have identified more than 150 mostly common variants associated with a variety of cancers. Prostate cancer, in particular, shows multiple associations with variants in homologous recombination dam age genes and with single nucleotide polymorphisms located in the intergenic or intronic regions of over a dozen loci in other genes. However, odds ratios for most of these associations are less than 2.0, and many are less than 1.3, therefore accounting for at most 20% of the observed familial risk for prostate cancer. Overall, then, although the role of inherited variants in the genome is clear, we cannot yet explain in detail the increased familial tendencies of most cancers. Whether common variants do not capture all of the risk or there are unrecognized environmental exposures in common between family members remains nonexclusive possibilities.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يقيم مهرجان الماء المعين السنوي الثالث في بغداد

على هامش المؤتمر التمهيدي لألفية الحوزة العلمية.. الهيأة العليا تقيم جلسة حوارية عن تراث الشيخ الطوسي

العتبة العباسية المقدسة تستعد لإقامة حفل التكليف الشرعي لتلميذات مدارس كربلاء

لليوم الثاني.. قسم التطوير يواصل تقديم دورة إعداد المدربين (TOT) لملاكات مديرية تربية كربلاء

المزيد

الآخبار الصحية

اللحظات الأخيرة قبل الموت.. هذا هو تسلسل "فقدان الحواس"

وخز الأطراف وضعف الذاكرة.. علامات على نقص فيتامين هام

عادة صباحية بسيطة.. تأثيرها قد يحسن ضغط الدم

عادات يومية تدمر قلبك بصمت.. خبراء يطلقون التحذير

المزيد

الآخبار التكنلوجية

الذكاء الاصطناعي يفك لغز آثار أقدام الديناصورات

القمر أولا.."سبيس إكس" تؤجل خططها الخاصة بالرحلات إلى المريخ

الذكور أم الإناث؟ دراسة "تنسف الشائع" بشأن التوحد

خبير يكشف عن اقتراب العلماء من فك شفرات "لغات الحيوانات" !

المزيد

مواضيع ذات صلة

Testing for Germline Pathogenic Variants Causing Hereditary Cancer

Pathogenic Variants in Tumor Suppressor Genes Causing Autosomal Recessive Pediatric Cancer Syndromes

Pathophysiology of Fanconi Anemia

Special Considerations in Treating Genetic Disease

The Current State of Treatment of Genetic Disease

Diseases Due to the expansion of Unstable Repeat Sequences

Normal Collagen Structure and Its Relationship to Osteogenesis Imperfecta

Cystic Fibrosis

Familial Hypercholesterolemia: A Genetic Hyperlipidemia

A Loss of Glycosylation: Mucolipidosis II or I-Cell Disease

Congenital Disorders of Glycosylation

The Example of Diseases Related to the X Chromosome: Hemophilia A and B