Group items tagged

“Intrinsic processes” include those that result in mutations due to random errors in DNA replication whereas “extrinsic factors” are environmental factors that affect mutagenesis rates (such as UV radiation, ionizing radiation, and carcinogens

intrinsic factors do not play a major causal role.

intrinsic cancer risk should be determined by the cancer incidence for those cancers with the least risk in the entire group controlling for total stem cell divisions

if one or more cancers would feature a much higher cancer incidence, for example, lung cancer among smokers vs. non-smokers, then this most likely reflects additional (and probably extrinsic) risk factors (smoking in this case)

Particularly, for breast and prostate cancers, it has long been observed that large international geographical variations exist in their incidences (5-fold for breast cancer, 25-fold for prostate cancer)14, and immigrants moving from countries with lower cancer incidence to countries with higher cancer rates soon acquire the higher risk of their new country

Colorectal cancer is another high-incidence cancer that is widely considered to be an environmental disease17, with an estimated 75% or more colorectal cancer risk attributable to diet

melanoma, its risk ascribed to sun exposure is around 65–86%

non-melanoma basal and squamous skin cancers, ~90% is attributable to UV

75% of esophageal cancer, or head and neck cancer are caused by tobacco and alcohol

HPV may cause ~90% cases in cervical cancer23, ~90% cases in anal cancer24, and ~70% in oropharyngeal cancer

HBV and HCV may account for ~80% cases of hepatocellular carcinoma

H pylori may be responsible for 65–80% of gastric cancer

While a few cancers have relatively large proportions of intrinsic mutations (>50%), the majority of cancers have large proportions of extrinsic mutations, for example, ~100% for Myeloma, Lung and Thyroid cancers and ~80–90% for Bladder, Colorectal and Uterine cancers, indicating substantial contributions of carcinogen exposures in the development of most cancers

onsistent estimate of contribution of extrinsic factors of >70–90% in most common cancer types. This concordance lends significant credibility to the overall conclusion on the role of extrinsic factors in cancer development

no treatment-related deaths

the most common adverse events were anaemia (26 [70%]), fatigue (25 [68%]), and rash

hypothyroidism

hypothyroidism

nivolumab-related autoimmune hypothyroidism, which resolved after a short course of corticosteroids

No grade 3 or 4 adverse events occurred

Nivolumab resulted in objective responses in 24% of patients with metastatic SCCA

Historically, doublet chemotherapy with cisplatin and fluorouracil has been the most common treatment for patients with metastatic SCCA

our results suggest that immune checkpoint blockade agents might extend overall survival beyond currently available therapies, especially if provided early in the disease treatment course

the dose of nivolumab we used differs from the 2016 recommendation of a fixed 240 mg every 2 weeks

25% of patients develop distant metastases

most patients with localised SCCA are cured by chemoradiation

More than 90% of cases of SCCA are linked to prior infection with human papillomavirus (HPV)

Within tumour cells, HPV oncoproteins are immunogenic and can trigger an anti-tumour host immune response by recruitment of tumour-infiltrating lymphocytes

Tumour cells express PD-L1 and, on binding its inhibitory receptor PD-1 on the surface of T cells, downregulate T-cell activation and thwart the local anti-tumour immune response

Nivolumab is a humanised monoclonal antibody against PD-1 that disrupts this interaction, enabling T-cell cytotoxicity. It has activity as a monotherapy in advanced solid cancers, such as head and neck cancer, melanoma, non-small-cell lung cancer, and renal cell carcinoma