Common cancers share familial susceptibility: implications for cancer genetics and counselling

Yu, Hongyao; Christoph, Frank; Sundquist, Jan; Hemminki, Akseli; Hemminki, Kari

doi:10.1136/jmedgenet-2016-103932

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…Another variable with possible influence on the results is the family size. We assume however that familial risks would not be influenced because a 3‐generation analysis from this Database showed that the proportions of cancers were relatively uniform and without systematic trends, even when the family sizes varied from <5 to >60 individuals . The present results were internally credible because a clear ‘dose‐response’ relationship was observed in risk increase by the number of affected relatives with discordant cancer.…”

Section: Discussionsupporting

confidence: 48%

Concordant and discordant familial cancer: Familial risks, proportions and population impact

Christoph

Sundquist

et al. 2017

Intl Journal of Cancer

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Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.

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Section: Discussionsupporting

confidence: 48%

Concordant and discordant familial cancer: Familial risks, proportions and population impact

Christoph

Sundquist

et al. 2017

Intl Journal of Cancer

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“…The results for 'All cancers' were remarkably high, RR reaching 2.58 in Table 1 for families of three or more cancer patients, including female breast cancer. We have recently characterize familial risks for families presenting with various cancers, and the present results provide further evidence for shared familial risks between many cancers [20][21][22][23].…”

Section: Discussionsupporting

confidence: 57%

Familial associations of male breast cancer with other cancers

Zheng

Hemminki

et al. 2017

Breast Cancer Res Treat

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“…The population burden of familial cancer in such families (total 3,393 patients) is far higher than in families with concordant BC (26 patients). This is yet another evidence for shared familial risks between multiple cancers …”

Section: Discussionmentioning

confidence: 83%

Familial associations of female breast cancer with other cancers

Zheng

Hemminki

et al. 2017

Intl Journal of Cancer

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Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family-Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of BC patients. Joint p-values were calculated from independent analyses. The total number of familial BCs was 12,266, 14.9% with one first-degree relative with BC and 1.2% with at least 2 affected relatives. Ovarian and prostate cancers showed the strongest associations with BC (p-value <10 ). The p-value for melanoma was <10 , for stomach and male colorectal cancer <2.5 × 10 , for cancer of unknown primary <2.5 × 10 and for lung cancer <5 × 10 . Significance level <5 × 10 was reached with pancreatic cancer. The remaining associations (p < 0.0025) included thyroid, endometrial, testicular, eye cancers (uveal melanoma), nervous system and endocrine tumors and non-Hodgkin lymphoma. The RR for BC increased by increasing numbers of patients with any cancer in family members and it reached 1.62 when three or more family members were affected. The results suggest that BC shares susceptibility with a number of other cancers. This might alert genetic counselors and challenge approaches for gene and gene-environment identification.

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Common cancers share familial susceptibility: implications for cancer genetics and counselling

Abstract: A strong family history of cancer, regardless of tumour type, increases cancer risk of family members and calls for mechanistic explanations. Our data provide tools for counselling of patients with cancer with both low and high familiar risks.

Cited by 13 publications

References 23 publications

Concordant and discordant familial cancer: Familial risks, proportions and population impact

Concordant and discordant familial cancer: Familial risks, proportions and population impact

Familial associations of male breast cancer with other cancers

Familial associations of female breast cancer with other cancers

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